Beam manipulation for resonant plasma wakefield acceleration

Plasma-based acceleration has already proved the ability to reach ultra-high accelerating gradients. However the step towards the realization of a plasma-based accelerator still requires some e ff ort to guarantee high brightness beams, stability and reliability. A significant improvement in the efficiency of PWFA has been demonstrated so far accelerating a witness bunch in the wake of a higher charge driver bunch. The transformer ratio, therefore the energy transfer from the driver to the witness beam, can be increased by resonantly exciting the plasma with a properly pre-shaped drive electron beam. Theoretical and experimental studies of beam manipulation for resonant PWFA will be presented her

Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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Operational experience on the generation and control of high brightness electron bunch trains at SPARC-LAB

Sub-picosecond, high-brightness electron bunch trains are routinely produced at SPARC-LAB via the velocity bunching technique. Such bunch trains can be used to drive multi-color Free Electron Lasers (FELs) and plasma wake field accelerators. In this paper we present recent results at SPARC-LAB on the generation of such beams, highlighting the key points of our scheme. We will discuss also the on-going machine upgrades to allow driving FELs with plasma accelerated beams or with short electron pulses at an increased energy

High gradient ultra-high brightness RF photo-injector optimization

In the pasts decades particle accelerators and especially RF photoinjectors had an impressive development, thanks to which a lot of applications were possible from the industrial one up to the medical use. Historically accelerators were developed for nuclear and particles physics but nowadays only a small part of accelerators are devoted to science, most of them are used for applications. The current request for scientific scope, especially for particle physics, is an higher and higher beam energy. The energy scale of TeV in the center of mass, in the past decades was reached. In the most recent and powerful proton particle accelerator Large Hadron Collider (LHC), was reached the impressive energy value in the center of mass of about 13 TeV and a Luminosity of about 10^34 cm^−2s^−1. The energy request from the scientific community has led to some accelerators project that exceed 50 Km lenght. In order to overcome these accelerator dimensions and especially to reduce costs, a good solution is the plasma acceleration. With this new accelerator technique the accelerating gradients can be a factor 10^3 more intense with respect to the modern RF technology. Nowadays plasma acceleration does not look like a chimera anymore, it was been demonstrated as a proof of principle but a lot of work is still to do in order to reach a good beam quality such that it can be used in accelerator facilities and in applications. Most of the applications in fact demand an high beam quality: ultra low energy spread and ultra high brightness beams. High brightness beams means bunches with an high peak current and a low emittance. These quality parameters are also necessary in order to perform a good matching between beams from accelerator and plasma in the so called external injection scheme for plasma acceleration. For example the energy spread that a bunch acquires during the acceleration is proportional to the length of the bunch that is injected into the plasma. Furthermore with a low transverse emittance the beam can be easily focused in order to reach the transverse matching conditions between beam and plasma. Beam brightness is a fundamental parameter for applications as the Free Electron Laser (FEL) that is able to produce X rays, where the gain length (Lg) is inversely proportional to the electron beam brightness (Lg proportional to B^−1/3) in the Self Amplified Spontaneous Emission (SASE) X-ray regime. These requests in the electron beam quality means that a perfect control of the bunches along the beam line is necessary, starting from the bunch generation in an electron gun up to the accelerator end, especially in the photoinjector region where the beam is not yet relativistic and is in the so called space charge regime. From these requests the beam transport has to be optimized, especially at low energies, performing a fine tuning of the machine parameters and of the positions of the machine elements along the beam line. To do that have to be fixed: a proper position for the first accelerating section, an integrated magnetic field of the gun solenoid, an optimal bunch compression scheme and mostly avoid any misalignments of the accelerating sections and of any magnetic components. In the photoinjector, where the beam is not yet relativistic, any misalignments can generate a transverse kick of the entire beam and a distortion of the beam transverse shape. The bunch can easily degrade its quality parameters in the photoinjector region, which in case of standard applications (e.g. industrial or medical) could be not so detrimental. Differently in case of applications as the ones here discussed (plasma acceleration or FEL) it is a serious matter which compromise the application itself. One of the effects of a low beam quality is a more difficult matching with the linac and subsequently with the plasma channel. In order to meet these stringent beam quality parameter requests, I optimized the beam dynamics of a new ultra high gradient 1.6 cells C-band (5.712 GHz) gun able to reach 240 MV/m as a peak field. By means of the ultra high gradient a better control of the space charge forces inside the bunch is possible. After optimizations on this electron gun a proper emittance compensation scheme was found through simulations with the software General Particle Tracer (GPT). Simulations showed the possibility to have, with a 100 pC beam and an energy of about 150 MeV, an emittance value of about 55 nm and a final beam brightness value of about 5 × 10^16 A/m^2. In order to optimize the present and future SPARC_LAB beam line, I wrote an algorithm able to evaluate transverse misalignments of a gun solenoid with coils powered with opposite currents. This algorithm was checked successfully in a dedicated run at SPARC_LAB. Using this algorithm the estimation of misalignements was about 1 mm and 0.5 mm in the transverse planes. During the SPARC_LAB machine operations we measure a bunch centroid displacement due to the misaligned solenoid. Aligning the solenoid to the found values we will improve the centroid orbit displacement of about 99.4%. Furthermore it will be possible avoid transverse kicks and distortions of the transverse beam shape and emittances i.e. the fundamental parameters to match simultaneously the beam with plasma in both transverse planes. The beam can have different spots and emittances in the x, y transverse planes due to laser on cathode misalignments, or due to some residual misalignements on the gun solenoid or on accelerating sections. I studied the possibility to insert Printed Circuit(PC) skew quadrupoles inside the future SPARC_LAB gun solenoid. By GPT simulations these PC skew quadrupoles will be able to reduce spot differences in the x and y planes, from 14% up to about 1% and a differences in the emittances, in x versus y plane, from 14% up to 5%. A first design of these PC quadrupoles was made, and we are planning to install them in the future SPARC_LAB gun solenoid

Beam dynamics in resonant plasma wakefield acceleration at SPARC_LAB

Strategies to mitigate the increase of witness emittance and energy spread in beam driven plasma wakefield acceleration are investigated. Starting from the proposed resonant wakefield acceleration scheme in quasi-non-linear regime that is going to be carried out at SPARC_LAB, we performed systematic scans of the parameters to be used for drivers. The analysis will show that one of the main requirements to preserve witness quality during the acceleration is to have accelerating and focusing fields that are very stable during all the accelerating length. The difference between the dynamics of the leading bunch and the trailing bunch is pointed out. The classical condition on bunch length k(p)sigma(z) = root 2 seems to be an ideal condition for the first driver within long accelerating lengths. The other drivers show to follow different longitudinal matching conditions. In the end a new method for the investigation of the matching for the first driver is introduced

Immunogenicity of <i>Escherichia coli</i> Outer Membrane Vesicles: Elucidation of Humoral Responses against OMV-Associated Antigens

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria have emerged as a novel and flexible vaccine platform. OMVs can be decorated with foreign antigens and carry potent immunostimulatory components. Therefore, after their purification from the culture supernatant, they are ready to be formulated for vaccine use. It has been extensively demonstrated that immunization with engineered OMVs can elicit excellent antibody responses against the heterologous antigens. However, the definition of the conditions necessary to reach the optimal antibody titers still needs to be investigated. Here, we defined the protein concentrations required to induce antigen-specific antibodies, and the amount of antigen and OMVs necessary and sufficient to elicit saturating levels of antigen-specific antibodies. Since not all antigens can be expressed in OMVs, we also investigated the effectiveness of vaccines in which OMVs and purified antigens are mixed together without using any procedure for their physical association. Our data show that in most of the cases OMV–antigen mixtures are very effective in eliciting antigen-specific antibodies. This is probably due to the capacity of OMVs to “absorb” antigens, establishing sufficiently stable interactions that allow antigen–OMV co-presentation to the same antigen presenting cell. In those cases when antigen–OMV interaction is not sufficiently stable, the addition of alum to the formulation guarantees the elicitation of high titers of antigen-specific antibodies

Scaling of Beam Collective Effects with Bunch Charge in the CompactLight Free-Electron Laser

The CompactLight European consortium is designing a state-of-the-art X-ray free-electron laser driven by radiofrequency X-band technology. Rooted in experimental data on photo-injector performance in the recent literature, this study estimates analytically and numerically the performance of the CompactLight delivery system for bunch charges in the range 75-300 pC. Space-charge forces in the injector, linac transverse wakefield, and coherent synchrotron radiation in bunch compressors are all taken into account. The study confirms efficient lasing in the soft X-rays regime with pulse energies up to hundreds of microjoules at repetition rates as high as 1 kHz

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

OBJECTIVES To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. METHODS Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. RESULTS Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4CXC-motif chemokine receptor 5 (CXCR5)programmed cell death protein 1 (PD1)ICOS Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4CD45ROICOSPD1 cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5CD4PD1ICOSFoxp3 Tfh-cells and a uniquely expanded population of CXCR5CD4PD1ICOSFoxp3 Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). CONCLUSIONS Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS