Dimuon production by laser-wakefield accelerated electrons

We analyze $\mu^+\mu^-$ pair production generated by high-energy electrons emerging from a laser-wakefield accelerator. The $\mu^+\mu^-$ pairs are created in a solid thick high-$Z$ target, following the electron accelerating plasma region. Numerical estimates are presented for electron beams obtained presently in the LBL TW laser experiment \cite{C2} and possible future developments. Reactions induced by the secondary bremsstrahlung photons dominate the dimuon production. According to our estimates, a 20 pC electron bunch with energy of 1 (10) GeV may create about 200 (6000) muon pairs. The produced $\mu^\pm$ can be used in studying various aspects of muon-related physics in table top installations. This may be considered as an important step towards the investigation of more complicated elementary processes induced by laser driven electrons.Comment: 14 pages, 5 figure

Formation of Pillars at the Boundaries between H II Regions and Molecular Clouds

We investigate numerically the hydrodynamic instability of an ionization front (IF) accelerating into a molecular cloud, with imposed initial perturbations of different amplitudes. When the initial amplitude is small, the imposed perturbation is completely stabilized and does not grow. When the initial perturbation amplitude is large enough, roughly the ratio of the initial amplitude to wavelength is greater than 0.02, portions of the IF temporarily separate from the molecular cloud surface, locally decreasing the ablation pressure. This causes the appearance of a large, warm HI region and triggers nonlinear dynamics of the IF. The local difference of the ablation pressure and acceleration enhances the appearance and growth of a multimode perturbation. The stabilization usually seen at the IF in the linear regimes does not work due to the mismatch of the modes of the perturbations at the cloud surface and in density in HII region above the cloud surface. Molecular pillars are observed in the late stages of the large amplitude perturbation case. The velocity gradient in the pillars is in reasonably good agreement with that observed in the Eagle Nebula. The initial perturbation is imposed in three different ways: in density, in incident photon number flux, and in the surface shape. All cases show both stabilization for a small initial perturbation and large growth of the second harmonic by increasing amplitude of the initial perturbation above a critical value.Comment: 21 pages, 8 figures, accepted for publication in ApJ. high resolution figures available upon reques

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

Spherical shock in the presence of an external magnetic field

We investigate spherical collisionless shocks in the presence of an external magnetic field. Spherical collisionless shocks are common resultant of interactions between a expanding plasma and a surrounding plasma, such as the solar wind, stellar winds, and supernova remnants. Anisotropies often observed in shock propagations and their emissions, and it is widely believed a magnetic field plays a major role. Since the local observations of magnetic fields in astrophysical plasmas are not accessible, laboratory experiments provide unique capability to investigate such phenomena. We model the spherical shocks in the universe by irradiating a solid spherical target surrounded by a plasma in the presence of a magnetic field. We present preliminary results obtained by shadowgraphy

Proton imaging of an electrostatic field structure formed in laser-produced counter-streaming plasmas

We report the measurements of electrostatic field structures associated with an electrostatic shock formed in laser-produced counter-streaming plasmas with proton imaging. The thickness of the electrostatic structure is estimated from proton images with different proton kinetic energies from 4.7 MeV to 10.7 MeV. The width of the transition region is characterized by electron scale length in the laser-produced plasma, suggesting that the field structure is formed due to a collisionless electrostatic shock

Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P(1) receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility

Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

<p>Abstract</p> <p>Background</p> <p>Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats.</p> <p>Results</p> <p>Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a <it>P</it>-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail.</p> <p>Conclusion</p> <p>The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks.</p