Investigation on the origin of hot electrons in laser plasma interaction at shock ignition intensities.

Shock Ignition is a two-step scheme to reach Inertial Confinement Fusion, where the precompressed fuel capsule is ignited by a strong shock driven by a laser pulse at an intensity in the order of [Formula: see text] W/cm[Formula: see text]. In this report we describe the results of an experiment carried out at PALS laser facility designed to investigate the origin of hot electrons in laser-plasma interaction at intensities and plasma temperatures expected for Shock Ignition. A detailed time- and spectrally-resolved characterization of Stimulated Raman Scattering and Two Plasmon Decay instabilities, as well as of the generated hot electrons, suggest that Stimulated Raman Scattering is the dominant source of hot electrons via the damping of daughter plasma waves. The temperature dependence of laser plasma instabilities was also investigated, enabled by the use of different ablator materials, suggesting that Two Plasmon Decay is damped at earlier times for higher plasma temperatures, accompanied by an earlier ignition of SRS. The identification of the predominant hot electron source and the effect of plasma temperature on laser plasma interaction, here investigated, are extremely useful for developing the mitigation strategies for reducing the impact of hot electrons on the fuel ignition.

High-repetition rate solid target delivery system for PW-class laser-matter interaction at ELI Beamlines.

L3-HAPLS (High-repetition-rate Advanced Petawatt Laser System) at ELI (Extreme Light Infrastructure) Beamlines currently delivers 0.45 PW pulses (12 J in 27 fs) at 3.3 Hz repetition rate. A fresh target surface for every shot was placed at the laser focus using an in-house tape target system designed to withstand large laser intensities and energies. It has been tested for different material thicknesses (25 and 7.6 µm), while L3-HAPLS delivered laser shots for energies ranging from 1 to 12 J. A technical description of the tape target system is given. The device can be used in diverse geometries needed for laser-matter interaction studies by providing an ≈300° free angle of view on the target in the equatorial plane. We show experimental data demonstrating the shot-to-shot stability of the device. An x-ray crystal spherical spectrometer was set up to measure the Kα yield stability, while a GHz H-field probe was used to check the shot-to-shot electromagnetic pulse generation. Finally, we discuss short and mid-term future improvements of the tape target system for efficient user operation.

Characterization of suprathermal electrons inside a laser accelerated plasma via highly-resolved K⍺-emission.

Suprathermal electrons are routinely generated in high-intensity laser produced plasmas via instabilities driven by non-linear laser-plasma interaction. Their accurate characterization is crucial for the performance of inertial confinement fusion as well as for performing experiments in laboratory astrophysics and in general high-energy-density physics. Here, we present studies of non-thermal atomic states excited by suprathermal electrons in kJ-ns-laser produced plasmas. Highly spatially and spectrally resolved X-ray emission from the laser-deflected part of the warm dense Cu foil visualized the hot electrons. A multi-scale two-dimensional hydrodynamic simulation including non-linear laser-plasma interactions and hot electron propagation has provided an input for ab initio non-thermal atomic simulations. The analysis revealed a significant delay between the maximum of laser pulse and presence of suprathermal electrons. Agreement between spectroscopic signatures and simulations demonstrates that combination of advanced high-resolution X-ray spectroscopy and non-thermal atomic physics offers a promising method to characterize suprathermal electrons inside the solid density matter.

Magnetized plasma implosion in a snail target driven by a moderate-intensity laser pulse.

Optical generation of compact magnetized plasma structures is studied in the moderate intensity domain. A sub-ns laser beam irradiated snail-shaped targets with the intensity of about 1016 W/cm2. With a neat optical diagnostics, a sub-megagauss magnetized plasmoid is traced inside the target. On the observed hydrodynamic time scale, the hot plasma formation achieves a theta-pinch-like density and magnetic field distribution, which implodes into the target interior. This simple and elegant plasma magnetization scheme in the moderate-intensity domain is of particular interest for fundamental astrophysical-related studies and for development of future technologies.

Human TRIB2 is a repressor of FOXO that contributes to the malignant phenotype of melanoma cells.

FOXO transcription factors are evolutionarily conserved proteins that orchestrate gene expression programs known to control a variety of cellular processes such as cell cycle, apoptosis, DNA repair and protection from oxidative stress. As the abrogation of FOXO function is a key feature of many tumor cells, regulation of FOXO factors is receiving increasing attention in cancer research. In order to discover genes involved in the regulation of FOXO activity, we performed a large-scale RNA-mediated interference (RNAi) screen using cell-based reporter systems that monitor transcriptional activity and subcellular localization of FOXO. We identified genes previously implicated in phosphoinositide 3-kinase/Akt signaling events, which are known to be important for FOXO function. In addition, we discovered a previously unrecognized FOXO-repressor function of TRIB2, the mammalian homolog of the Drosophila gene tribbles. A cancer-profiling array revealed specific overexpression of TRIB2 in malignant melanoma, but not in other types of skin cancer. We provide experimental evidence that TRIB2 transcript levels correlate with the degree of cytoplasmic localization of FOXO3a. Moreover, we show that TRIB2 is important in the maintenance of the oncogenic properties of melanoma cells, as its silencing reduces cell proliferation, colony formation and wound healing. Tumor growth was also substantially reduced upon RNAi-mediated TRIB2 knockdown in an in vivo melanoma xenograft model. Our studies suggest that TRIB2 provides the melanoma cells with growth and survival advantages through the abrogation of FOXO function. Altogether, our results show the potential of large-scale cell-based RNAi screens to identify promising diagnostic markers and therapeutic targets.

Soft x-ray free electron laser microfocus for exploring matter under extreme conditions.

We have focused a beam (BL3) of FLASH (Free-electron LASer in Hamburg: lambda = 13.5 nm, pulse length 15 fs, pulse energy 10-40 microJ, 5 Hz) using a fine polished off-axis parabola having a focal length of 270 mm and coated with a Mo/Si multilayer with an initial reflectivity of 67% at 13.5 nm. The OAP was mounted and aligned with a picomotor controlled six-axis gimbal. Beam imprints on poly(methyl methacrylate) - PMMA were used to measure focus and the focused beam was used to create isochoric heating of various slab targets. Results show the focal spot has a diameter of < or =1 microm. Observations were correlated with simulations of best focus to provide further relevant information.

Genetic modelling of the PTEN/AKT pathway in cancer research

The focus on targeted therapies has been fuelled by extensive research on molecular pathways and their role in tumorigenesis. Novel models of human cancer have been created to evaluate the role of specific genes in the different stages of cancer. Currently, mouse modelling of human cancer is possible through the expression of oncogenes, specific genetic mutations or the inactivation of tumour suppressor genes, and these models have begun to provide us with an understanding of the molecular pathways involved in tumour initiation and progression at the physiological level. Additionally, these mouse models serve as an excellent system to evaluate the efficacy of currently developed molecular targeted therapies and identify new potential targets for future therapies. The PTEN/AKT pathway is implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein-linked receptors. Deregulation of the PTEN/AKT pathway is a common event in human cancer. Despite the abundant literature, the physiological role of each element of the pathway has begun to be uncovered thanks to genetically engineered mice. This review will summarise some of the key animal models which have helped us to understand this signalling network and its contribution to tumorigenesis (AU)

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Radiation transfer effects on the spectra of laser-generated plasmas.

Experimental x-ray spectra of the H-like 2p --> 1s (Lyman-alpha) doublet have been obtained using time-integrated high-resolution spectroscopy of a constrained-flow, laser-generated aluminum plasma. These spectra show monotonic alteration of the relative intensities of the doublet components with distance from the target surface. Excellent agreement between experiment and theory is found only if the modeling includes both ion collisional rates between the fine-structure components of the level and, more importantly, the radiative pumping of one Lyman-alpha component by the other component along the direction of the major velocity gradient (i.e., perpendicular to the direction of spectra observation). Understanding radiation transfer in plasmas with high velocity gradients is important in modeling many astrophysical objects, and this experiment acts as a benchmark for such complex calculations.

K-shell spectroscopy of an independently diagnosed uniaxially expanding laser-produced aluminum plasma.

We present detailed spectroscopic analysis of the primary K-shell emission lines from a uniaxially expanding laser-produced hydrogenic and heliumlike aluminum plasma. The spectroscopic measurements are found to be consistent with time-dependent hydrodynamic properties of the plasma, measured using Thomson scattering and shadowgraphy. The K-shell population kinetics code FLY with the measured hydrodynamic parameters is used to generate spectra that are compared to the experimental spectra. Excellent agreement is found between the measured and calculated spectra for a variety of experimental target widths employed to produce plasmas with different optical depths. The peak emission from the hydrogenic Lyman series is determined to be from a temporal and spatial region where the hydrodynamic parameters are essentially constant. This allows a single steady-state solution of FLY to be used to deduce the electron temperature and density, from the measured line ratios and linewidths, for comparison with the Thomson and shadowgraphy data. These measurements are found to agree well with time-dependent calculations, and provide further validation for the FLY calculations of the ionization and excitation balance for a K-shell aluminum plasma. We also discuss the possible application of this data as a benchmark for hydrodynamic simulations and ionization/excitation balance calculations.

Upregulation of the cochaperone Mdg1 in endothelial cells is induced by stress and during in vitro angiogenesis.

Angiogenesis research has focused on receptors and ligands mediating endothelial cell proliferation and migration. Little is known about the molecular mechanisms that are involved in converting endothelial cells from a proliferative to a differentiated state. Microvascular differentiation gene 1 (Mdg1) has been isolated from differentiating microvascular endothelial cells that had been cultured in collagen type I gels (3D culture). In adult human tissue Mdg1 is expressed in endothelial and epithelial cells. Sequence analysis of the full-length cDNA revealed that the N-terminal region of the putative Mdg1-protein exhibits a high sequence similarity to the J-domain of Hsp40 chaperones. We show that this region functions as a bona fide J-domain as it can replace the J-domain of Escherichia coli DnaJ-protein. Mdg1 is also upregulated in primary endothelial and mesangial cells when subjected to various stress stimuli. GFP-Mdg1 fusion constructs showed the Mdg1-protein to be localized within the cytoplasm under control conditions. Stress induces the translocation of Mdg1 into the nucleus, where it accumulates in nucleoli. Costaining with Hdj1, Hdj2, Hsp70, and Hsc70 revealed that Mdg1 colocalizes with Hsp70 and Hdj1 in control and stressed HeLa cells. These data suggest that Mdg1 is involved in the control of cell cycle arrest taking place during terminal cell differentiation and under stress conditions.

The expression of constitutively active isotypes of protein kinase C to investigate preconditioning.

The role of protein kinase C (PKC) in ischemic preconditioning remains controversial because of difficulties with both its measurement and pharmacological manipulation. We investigated preconditioning in isolated neonatal rat cardiocytes by expressing constitutively active isotypes of PKC. Observations at differing durations of simulated ischemia suggested beta-galactosidase (beta-gal) activity reflected viability within transfected myocytes. Preconditioning with 90 min of ischemia significantly increased beta-gal activity and myocyte survival after 6 h of ischemia; an effect abolished by PKC inhibitors. After co-transfection with plasmids encoding beta-gal and either constitutively active mutants of PKC-delta, PKC-alpha, wild type PKC-delta, or empty vector, cardiocytes were subjected to 6 h of ischemia. Only PKC-delta, rendered constitutively active by a limited deletion within the pseudosubstrate domain, consistently increased resistance to simulated ischemia (beta-gal activity was 85.6 +/- 11.9% versus 53.7 +/- 6.5% (p

High-resolution x-ray imaging of extended lasing plasmas.

An x-ray imaging system with a bent focusing crystal was used for time-resolved one-dimensional imaging of a long plasma column of highly ionized aluminum. This scheme uses a focusing geometry with a spherically bent crystal and a slit on the Rowland circle. Alternative schemes of x-ray monochromatic imaging are briefly discussed. The homogeneity of the up to 40-mm-long laser-generated plasma column was studied with a temporal resolution of 100 ps. The potential spatial resolution of the instrument is 90 microm or better. Monochromatic images taken on the resonance He alpha line of Al XII characterize the homogeneity of a plasma generated to study a recombination x-ray laser scheme, giving an amplified spontaneous emission in Al XI.

Cellular proteins bind to the downstream component of the lytic origin of DNA replication of Epstein-Barr virus.

The lytic origin of DNA replication of Epstein-Barr virus, oriLyt, is a complex eukaryotic origin which is activated during the lytic phase of the viral life cycle. It consists of at least two independent cis-acting components, one of which plays a dual role in transcription and DNA replication. The binding of the viral factor BZLF1, a member of the AP1 family of transcription factors, to this upstream component is crucial for oriLyt function (A. Schepers, D. Pich, and W. Hammerschmidt, EMBO J. 12:3921-3929, 1993). The second cis-acting element, the downstream component of oriLyt, is equally indispensable; however, its function is unknown. In this study, the downstream component was found to be the binding target of several cellular proteins. One could be identified as Sp1 or as a related protein which binds twice to the downstream component of oriLyt. Mutational analysis indicated that Sp1 alone is not directly involved in mediating DNA replication; however, other factors which share the same binding sequence or bind closely to one of the Sp1 binding sites are likely candidates to contribute to a replication protein complex at the downstream component of oriLyt. The sequence requirements for the downstream component are remarkably stringent, indicating that at least one of the putative factors is a sequence-specific DNA-binding protein which is required for the activation of oriLyt.

Plasma and submandibular saliva lysosomal enzymes in cystic fibrosis.

This study determined in a blind fashion the activity levels and thermostability properties of two lysosomal hydrolytic enzymes, acid phosphatase and alpha-mannosidase, in plasma samples from 25 cystic fibrosis (CF) patients and 25 age- and sex-matched normal controls. Mean alpha-mannosidase activity (3.2 +/- 1.0 mU/ml) and acid phosphatase activities (6.5 +/- 2.9 mU/ml) in CF patients were not significantly different from those found in normal individuals (2.8 +/- 0.7 and 7.6 +/- 3.4 mU/ml, respectively). Using stringent conditions no differences in thermostability properties of these enzymes were found between plasma from CF patients as compared to that of normal controls. When activity levels of these enzymes and of four additional hydrolytic enzymes, alpha-L-fucosidase, alpha-galactosidase, alpha-glucosidase and beta-galactosidase, were determined in submandibular saliva, no significant differences in enzyme levels between CF and age- and sex-matched controls were noted nor were thermostability differences found. Our data do not support the concept that altered properties of these enzymes are useful as markers for detection of CF homozygotes and heterozygotes, nor the hypothesis that the defect underlying this disease is a deficiency of post-translational modification of glycoproteins leading to their mis-compartmentalization and qualitative alteration.