Calcitonin receptor-like receptor is expressed on gastrointestinal immune cells

Background/Aims: Pharmacological and morphological studies suggest that the gut mucosal immune system and local neuropeptide-containing neurones interact. We aimed to determine whether gut immune cells are targets for calcitonin gene-related peptide (CGRP), which has potent immune regulatory properties. Methods: Using density gradient centrifugation, rat lamina propria mononuclear cells (LP-MNCs) and intra-epithelial lymphocytes (IELs) were isolated. RT-PCR was employed for the detection of mRNA of rat calcitonin receptor-like receptor (CRLR), which is considered to represent the pharmacologically defined CGRP receptor-1 subtype, as well as mRNA of the receptor activity-modifying proteins, which are essential for CRLR function and determine ligand specificity. A radioreceptor assay was employed for the detection of specific CGRP binding sites. Results: RT-PCR and DNA sequencing showed that LP-MNCs and IELs express CRLR. Incubation of isolated LP-MNCs with radiolabelled alphaCGRP revealed the existence of specific binding sites for CGRP. Conclusion: These novel data indicate that mucosal immune cells of the rat gut are a target for CGRP and provide significant evidence that CGRP functions as an immune regulator in the gut mucosa. Copyright (C) 2002 S. Karger AG, Basel

Ion acceleration from laser-driven electrostatic shocks

Multi-dimensional particle-in-cell simulations are used to study the generation of electrostatic shocks in plasma and the reflection of background ions to produce high-quality and high-energy ion beams. Electrostatic shocks are driven by the interaction of two plasmas with different density and/or relative drift velocity. The energy and number of ions reflected by the shock increase with increasing density ratio and relative drift velocity between the two interacting plasmas. It is shown that the interaction of intense lasers with tailored near-critical density plasmas allows for the efficient heating of the plasma electrons and steepening of the plasma profile at the critical density interface, leading to the generation of high-velocity shock structures and high-energy ion beams. Our results indicate that high-quality 200 MeV shock-accelerated ion beams required for medical applications may be obtained with current laser systems.Comment: 33 pages, 12 figures, accepted for publication in Physics of Plasma

Laser-driven shock acceleration of monoenergetic ion beams

We show that monoenergetic ion beams can be accelerated by moderate Mach number collisionless, electrostatic shocks propagating in a long scale-length exponentially decaying plasma profile. Strong plasma heating and density steepening produced by an intense laser pulse near the critical density can launch such shocks that propagate in the extended plasma at high velocities. The generation of a monoenergetic ion beam is possible due to the small and constant sheath electric field associated with the slowly decreasing density profile. The conditions for the acceleration of high-quality, energetic ion beams are identified through theory and multidimensional particle-in-cell simulations. The scaling of the ion energy with laser intensity shows that it is possible to generate $\sim 200$ MeV proton beams with state-of-the-art 100 TW class laser systems.Comment: 13 pages, 4 figures, accepted for publication in Physical Review Letter

Improved Filters for Angular Filter Refractometry

Angular filter refractometry is an optical diagnostic that measures absolute contours of line-integrated density gradient by placing a filter with alternating opaque and transparent zones in the focal plane of a probe beam, which produce corresponding alternating light and dark regions in the image plane. Identifying transitions between these regions with specific zones on the angular filter (AF) allows the line-integrated density to be determined, but the sign of the density gradient at each transition is degenerate and must be broken using other information about the object plasma. Additional features from diffraction in the filter plane often complicate data analysis. In this paper, we present an improved AF design that uses a stochastic pixel pattern with a sinusoidal radial profile to minimize unwanted diffraction effects in the image caused by the sharp edges of the filter bands. We also present a technique in which a pair of AFs with different patterns on two branches of the same probe beam can be used to break the density gradient degeneracy. Both techniques are demonstrated using a synthetic diagnostic and data collected on the OMEGA EP laser

A complementary compact laser based neutron source

Several experiments of neutron generation using high intensity laser sources, with a power exceeding 10^19W/cm^2 via TNSA (Target Normal Sheath Acceleration) or other similar methods, have been performed in the past years in different laboratories. However, so far there is no one running neutron source based on such a technology. In the framework of the Conceptual Report Design of a new accelerator in the Eupraxia project we are studying the possibility to have a laser-based neutron source, not only by TNSA but also from self-injection schemes. We focus our attention on the applications in cultural heritage studies as well also on the complementary role that such a source can have in the framework of large facilities devoted to radiation production.Comment: 4 pages, two figures, 3rd European Advanced Accelerators Concept

Collisionless shock acceleration of narrow energy spread ion beams from mixed species plasmas using 1 μ\mum lasers

Collisionless shock acceleration of protons and C$^{6+}$ ions has been achieved by the interaction of a 10$^{20}$ W/cm$^2$, 1 $\mu$m laser with a near-critical density plasma. Ablation of the initially solid density target by a secondary laser allowed for systematic control of the plasma profile. This enabled the production of beams with peaked spectra with energies of 10-18 MeV/a.m.u. and energy spreads of 10-20$\%$ with up to 3x10$^9$ particles within these narrow spectral features. The narrow energy spread and similar velocity of ion species with different charge-to-mass ratio are consistent with acceleration by the moving potential of a shock wave. Particle-in-cell simulations show shock accelerated beams of protons and C$^{6+}$ ions with energy distributions consistent with the experiments. Simulations further indicate the plasma profile determines the trade-off between the beam charge and energy and that with additional target optimization narrow energy spread beams exceeding 100 MeV/a.m.u. can be produced using the same laser conditions.Comment: Accepted for publication in Physical Review Accelerators and Beam

Potential link between the Sphingosine-1-Phosphate (S1P) system and defective alveolar macrophage phagocytic function in Chronic Obstructive Pulmonary Disease (COPD)

We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke. The exact mechanisms for this defect are unknown. Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P) are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function.We compared mRNA expression of sphingosine kinases (SPHK1/2), S1P receptors (S1PR1-5) and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1) in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers) using Real-Time PCR. Phagocytosis of apoptotic cells was investigated using flow cytometry. Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD. To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5. The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model.We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively), S1PR2 and 5 (4.3- and 14.6-fold increases respectively), and SGPL1 (4.5-fold increase) in COPD vs. controls. S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD "disease effect" rather than smoke effect per se. Significant associations were noted between S1PR5 and both lung function and phagocytosis. Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient-derived macrophages. Antagonising SIPR5 significantly improved phagocytosis.Our results suggest a potential link between the S1P signalling system and defective macrophage phagocytic function in COPD and advise therapeutic targets.Jameel Barnawi, Hai Tran, Hubertus Jersmann, Stuart Pitson, Eugene Roscioli, Greg Hodge, Robyn Meech, Rainer Haberberger, Sandra Hodg