The ELIMED transport and dosimetry beamline for laser-driven ion beams Romano, F.; Schillaci, F.; Cirrone, G.A.P. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
09/2016, Letnik:
829
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A growing interest of the scientific community towards multidisciplinary applications of laser-driven beams has led to the development of several projects aiming to demonstrate the possible use of ...these beams for therapeutic purposes. Nevertheless, laser-accelerated particles differ from the conventional beams typically used for multiscipilinary and medical applications, due to the wide energy spread, the angular divergence and the extremely intense pulses. The peculiarities of optically accelerated beams led to develop new strategies and advanced techniques for transport, diagnostics and dosimetry of the accelerated particles. In this framework, the realization of the ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) beamline, developed by INFN-LNS (Catania, Italy) and that will be installed in 2017 as a part of the ELIMAIA beamline at the ELI-Beamlines (Extreme Light Infrastructure Beamlines) facility in Prague, has the aim to investigate the feasibility of using laser-driven ion beams for multidisciplinary applications. In this contribution, an overview of the beamline along with a detailed description of the main transport elements as well as the detectors composing the final section of the beamline will be presented.
Interleukin-8 (IL-8) is one of the major mediators of the inflammatory response. The pathways by which IL-8 activates inositide-specific phospholipase C (PLC) were investigated by co-expression of ...different components of the guanosine triphosphate binding protein (G protein) pathway in COS-7 cells. Two distinct IL-8 receptors reconstituted ligand-dependent activation of endogenous PLC when transfected together with the G protein α subunits G$\alpha_{14}$, G$\alpha_{15}$, or G$\alpha_{16}$. However, reconstitution was not observed with cells that overexpressed G$\alpha_q$ or G$\alpha_{11}$. Furthermore, IL-8 receptors interacted with endogenous pertussis toxin-sensitive G proteins or with the recombinant G protein G$_i$ to release free βγ subunits that could then specifically activate the β2 isoform of PLC. These findings suggest that IL-8 acts through signal-transducing pathways that are limited to specific heterotrimeric G proteins and effectors. These may provide suitable targets for the development of anti-inflammatory agents.
Eosinophil leukocytes express high numbers of the chemokine receptor CCR3 which binds eotaxin, monocyte chemotactic protein (MCP)-4, and some other CC chemokines. In this paper we show that CCR3 is ...also highly expressed on human blood basophils, as indicated by Northern blotting and flow cytometry, and mediates mainly chemotaxis. Eotaxin and MCP-4 elicited basophil migration in vitro with similar efficacy as regulated upon activation normal T cells expressed and secreted (RANTES) and MCP-3. They also induced the release of histamine and leukotrienes in IL-3-primed basophils, but their efficacy was lower than that of MCP-1 and MCP-3, which were the most potent stimuli of exocytosis. Pretreatment of the basophils with a CCR3-blocking antibody abrogated the migration induced by eotaxin, RANTES, and by low to optimal concentrations of MCP-4, but decreased only minimally the response to MCP-3. The CCR3-blocking antibody also affected exocytosis: it abrogated histamine and leukotriene release induced by eotaxin, and partially inhibited the response to RANTES and MCP-4. In contrast, the antibody did not affect the responses induced by MCP-1, MCP-3, and macrophage inflammatory protein-1alpha, which may depend on CCR1 and CCR2, two additional receptors detected by Northern blotting with basophil RNA. This study demonstrates that CCR3 is the major receptor for eotaxin, RANTES, and MCP-4 in human basophils, and suggests that basophils and eosinophils, which are the characteristic effector cells of allergic inflammation, depend largely on CCR3 for migration towards different chemokines into inflamed tissues.
•Laser-driven beams as alternative source for hadrontherapy applications.•Monte Carlo simulations of the ELIMED beam line for optically accelerated beams.•Spatial dose distributions optimization at ...the irradiation point.•Calculation of dose delivered per shot for energies of clinical relevance.
The main purpose of this paper is to quantitatively study the possibility of delivering dose distributions of clinical relevance with laser-driven proton beams. A Monte Carlo application has been developed with the Geant4 toolkit, simulating the ELIMED (MEDical and multidisciplinary application at ELI-Beamlines) transport and dosimetry beam line which is being currently installed at the ELI-Beamlines in Prague (CZ). The beam line will be used to perform irradiations for multidisciplinary studies, with the purpose of demonstrating the possible use of optically accelerated ion beams for therapeutic purposes. The ELIMED Geant4-based application, already validated against reference transport codes, accurately simulates each single element of the beam line, necessary to collect the accelerated beams and to select them in energy. Transversal dose distributions at the irradiation point have been studied and optimized to try to quantitatively answer the question if such kind of beam lines, and specifically the systems developed for ELIMED in Prague, will be actually able to transport ion beams not only for multidisciplinary applications, such as pitcher-catcher nuclear reactions (e.g. neutrons), PIXE analysis for cultural heritage and space radiation, but also for delivering dose patterns of clinical relevance in a future perspective of possible medical applications.
Extreme lateral interbody fusion allows for the insertion of a large‐footprint interbody cage while maintaining the presence of natural stabilizing ligaments and the facets. It is unclear how the ...load‐distribution mechanisms through these structures alter with temporal changes in the bone graft. The aim of this study was to examine the effects of temporal bone graft changes on load distribution among the cage, graft, and surrounding spinal structures using finite element analysis. Thoracolumbosacral spine computed tomography data from an asymptomatic male subject were segmented into anatomical regions of interest and digitally stitched to generate a surface mesh of the lumbar spine (L1‐S1). The interbody cage was inserted into the L4‐L5 region during surface meshing. A volumetric mesh was generated and imported into finite element software for pre‐processing, running nonlinear static solves, and post‐processing. Temporal stiffening was simulated in the graft region with unbonded (Soft Callus, Temporal Stages 1–3, Solid Graft) and bonded (Partial Fusion, Full Fusion) contact. In flexion and extension, cage stress reduced by 20% from the soft callus to solid graft state. Force on the graft was directly related to its stiffness, and load‐share between the cage and graft improved with increasing graft stiffness, regardless of whether contact was fused with the endplates. Fused contact between the cage‐graft complex and the adjacent endplates shifted load‐distribution pathways from the ligaments and facets to the implant, however, these changes did not extend to adjacent levels. These results suggest that once complete fusion is achieved, the existing load paths are seemingly diminished.
Nowadays, one of the biggest challenges consists in using high intensity laser-target interaction to generate high-energy ions for medical purposes, eventually replacing the old paradigm of ...acceleration characterized by huge and complex machines. In order to investigate the feasibility of using laser-driven ion beams for multidisciplinary application, a dedicated beam transport line will be installed at the ELI-Beamlines facility in Prague (CZ), as a part of the User-oriented ELIMAIA beam-line dedicated to ion acceleration and their potential applications. The beam-line section dedicated to transport and dosimetric endpoints is called ELIMED (ELI-Beamlines MEDical and multidisciplinary applications) and will be developed by the INFN-LNS.
Chemokines bind and signal through G-protein coupled seven transmembrane receptors. Various chemokine receptors are expressed on leukocytes, and these may impart selective homing of leukocyte subsets ...to sites of inflammation. Human eosinophils express the eotaxin receptor, CCR3, but respond to a variety of CC chemokines apart from eotaxin, including RANTES, monocyte chemotactic protein (MCP)-2, MCP-3, and MCP-4. Here we describe a mAb, 7B11, that is selective for CCR3 and has the properties of a true receptor antagonist. 7B11 blocked binding of various radiolabeled chemokines to either CCR3 transfectants, or eosinophils. Pretreatment of eosinophils with this mAb blocked chemotaxis and calcium flux induced by all CCR3 ligands. In all individuals examined, including allergic and eosinophilic donors, > 95% of the response of eosinophils to eotaxin, RANTES, MCP-2, MCP-3, and MCP-4 was shown to be mediated through CCR3. The IL-8 receptors, particularly CXCR2, were induced on IL-5 primed eosinophils, however these eosinophils responded to CC chemokines in the same manner as unprimed eosinophils. These results demonstrate the importance of CCR3 for eosinophil responses, and the feasibility of completely antagonizing this receptor.
A compact acoustic calibrator for ultra-high energy neutrino detection Adrián-Martínez, S.; Ardid, M.; Bou-Cabo, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2013, Letnik:
725
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With the aim to optimize and test the method of acoustic detection of ultra-high energy neutrinos in underwater telescopes a compact acoustic transmitter array has been developed. The acoustic ...parametric effect is used to reproduce the acoustic signature of an ultra-high-energy neutrino interaction. Different R&D studies are presented in order to show the viability of the parametric sources technique to deal with the difficulties of the acoustic signal generation: a very directive transient bipolar signal with ‘pancake’ directivity. The design, construction and characterization of the prototype are described, including simulation of the propagation of an experimental signal, measured in a pool, over a distance of 1km. Following these studies, next steps will be testing the device in situ, in underwater neutrino telescope, or from a vessel in a sea campaign.
Extreme lateral interbody fusion (XLIF) may be performed with a standalone interbody cage, or with the addition of unilateral or bilateral pedicle screws; however, decisions regarding supplemental ...fixation are predominantly based on clinical indicators. This study examines the impact of posterior supplemental fixation on facet micromotions, cage loads and load-patterns at adjacent levels in a L4-L5 XLIF at early and late fusion stages. CT data from an asymptomatic subject were segmented into anatomical regions and digitally stitched into a surface mesh of the lumbosacral spine (L1-S1). The interbody cage and posterior instrumentation (unilateral and bilateral) were inserted at L4-L5. The volumetric mesh was imported into finite element software for pre-processing, running nonlinear static solves and post-processing. Loads and micromotions at the index-level facets reduced commensurately with the extent of posterior fixation accompanying the XLIF, while load-pattern changes observed at adjacent facets may be anatomically dependent. In flexion at partial fusion, compressive stress on the cage reduced by 54% and 72% in unilateral and bilateral models respectively; in extension the reductions were 58% and 75% compared to standalone XLIF. A similar pattern was observed at full fusion. Unilateral fixation provided similar stability compared to bilateral, however there was a reduction in cage stress-risers with the bilateral instrumentation. No changes were found at adjacent discs. Posterior supplemental fixation alters biomechanics at the index and adjacent levels in a manner that warrants consideration alongside clinical information. Unilateral instrumentation is a more efficient option where the stability requirements and subsidence risk are not excessive.
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