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Laser wakefield accelerators (LWFAs) can produce high-energy electron bunches in short distances. Successfully coupling these sources with undulators has the potential to form an LWFA-driven free-electron laser (FEL), providing high-intensity short-wavelength radiation. Electron bunches produced from LWFAs have a correlated distribution in longitudinal phase space: a chirp. However, both LWFAs and FELs have strict parameter requirements. The bunch chirp created using ideal LWFA parameters may not suit the FEL; for example, a chirp can reduce the high peak current required for free-electron lasing. We, therefore, design a flexible beamline that can accept either positively or negatively chirped LWFA bunches and adjust the chirp during transport to an undulator. We have used the accelerator design program MAD8 to design a beamline in stages, and to track particle bunches. The final beamline design can produce ambidirectional values of longitudinal dispersion ([Formula: see text]): we demonstrate values of + 0.20 mm, 0.00  mm and - 0.22 mm. Positive or negative values of [Formula: see text] apply a shear forward or backward in the longitudinal phase space of the electron bunch, which provides control of the bunch chirp. This chirp control during the bunch transport gives an additional free parameter and marks a new approach to matching future LWFA-driven FELs., (© 2023. The Author(s).)

Attosecond duration relativistic electron bunches travelling through an undulator can generate brilliant coherent radiation in the visible to vacuum ultraviolet spectral range. We present comprehensive numerical simulations to study the properties of coherent emission for a wide range of electron energies and bunch durations, including space-charge effects. These demonstrate that electron bunches with r.m.s. duration of 50 as, nominal charge of 0.1 pC and energy range of 100-250 MeV produce [Formula: see text] coherent photons per pulse in the 100-600 nm wavelength range. We show that this can be enhanced substantially by self-compressing negatively chirped 100 pC bunches in the undulator to produce [Formula: see text] coherent photons with pulse duration of 0.5-3 fs., (© 2021. The Author(s).)

Introduction: Cyclotron-based proton therapy facilities use an energy degrader of variable thickness to deliver beams of the different energies required by a patient treatment plan; scattering and straggling in the degrader give rise to an inherent emittance increase and subsequent particle loss in the downstream energy-selection system (ESS). Here we study alternative graphite degrader geometries and examine with Monte-Carlo simulations the induced emittance growth and consequent particle transmission., Methods: We examined the conventional multiple-wedge degrader used in the Paul Scherrer Institute PROSCAN proton therapy system, the equivalent parallel-sided degrader, and a single block degrader of equivalent thickness. G4Beamline Monte-Carlo tracking of protons was benchmarked against measurements of the existing degrader for proton energies from 75 to 230 MeV, and used to validate simulations of the alternative geometries., Results: Using a careful calculation of the beam emittance growth, we determined that a single-block degrader placed close to the collimators of the ESS is expected to deliver significantly larger transmission, up to 17% larger at 150 MeV. At the lowest deliverable of 75 MeV there is still a clear improvement in beam transmission., Conclusions: Whilst dose rates are not presently limited on the PROSCAN system at higher energies, a single-block degrader offers the ability to access either lower energies for treatment or a larger dose rate at 75 MeV in case transmission optimisation is desired. Single-block degraders should be considered for the delivery of low-energy protons from a cyclotron-based particle therapy system., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

This study investigated a range of phenol-formaldehyde-aniline-based pyrolysed carbon matrices and their component materials, for their ability to adsorb a range of inflammatory cytokines crucial to the progression of sepsis. The efficiency of adsorption of the target molecules from human plasma was assessed and compared to that of Adsorba 300C, a commercially available cellulose-coated activated charcoal. Results indicate that a number of the primary carbon/resin materials demonstrate efficient adsorption of the cytokines studied here (TNF, IL-6 and IL-8), comparable to other adsorbents under clinical investigation. Our findings also illustrate that these adsorbent capabilities are retained when the primary particles are combined to form a pyrolysed carbon matrix. This capability will enable the engineering of the carbon matrix porosity allowing a blend of carbonised particle combinations to be tailored for maximum adsorption of inflammatory cytokines. The present findings support further investigation of this carbon material as a combined carbon-based filtration/adsorbent device for direct blood purification.

The aim of the present study was to conduct a preliminary investigation into the blood biocompatibility of a novel, uncoated carbon for use in a filtration/adsorption device for the treatment of sepsis. Carbon well prototypes were manufactured from phenol-formaldehyde-aniline-based pyrolysed carbons using monolithic polymer technology. Inflammatory blood cell and plasma protein mediation of the inflammatory response were evaluated using the novel carbon prototypes and compared with dialyser membrane and tissue culture plate controls. Assays determining monocyte and granulocyte adhesion, platelet adhesion and activation, granulocyte activation and complement activation were performed. Preliminary findings suggest an adsorptive but passivating carbon surface. Moderate levels of monocyte and granulocytes adhesion were seen in conjunction with adsorption of plasma proteins to the carbon surface. Activation of granulocyte and adherent platelets was not detected and the complement cascade was not activated by the carbons, indicating a surface compatible with blood contact. The results support the further development of the proposed carbon-based device for the treatment of sepsis.

Metallothionein (MT) protects against the harmful effects of a wide spectrum of stress factors. The most studied of these factors is cadmium, whose toxicity is reduced on sequestration by MT. However, there is poorer consensus in the literature about protection afforded by MT against stressors other than cadmium. In this study, a CHO-K1 cell line continuously overexpressing MT (MToex) was developed in order to evaluate the relative protection afforded by MT against different toxic agents. Cadmium was used as a positive control and, as expected, the MToex cells were more than 13-fold more resistant to the effects of cadmium chloride than were wild-type (WT) cells using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay (IC50 values of 10 and 132 microM for WT and MToex cells, respectively). In contrast, overexpression of MT afforded no protection against mercuric chloride, staurosporine and hydrogen peroxide (IC50 values of about 50, 11 and 925 microM, respectively). Cd and Hg uptake by MToex and WT cells exposed to 1-10 microM of metal chloride was similar and yet a significant amount of these metals was associated with the cytosol MT fraction in the MToex cells but not in the WT cells. From this study it can be concluded that while MT overexpression protects against Cd toxicity, it has no influence on Hg, staurosporine or hydrogen peroxide toxicity and it is proposed that this reflects mechanistic differences of toxicity or depletion of labile intracellular zinc by the presence of excess binding ligand in the form of MT.