Note: femtosecond laser micromachining of straight and linearly tapered capillary discharge waveguides

Gas-filled capillary discharge waveguides are important structures in laser-plasma interaction applications, such as the laser wakefield accelerator. We present the methodology for applying femtosecond laser micromachining in the production of capillary channels (typically 200–300 μm in diameter and 30–40 mm in length), including the formalism for capillaries with a linearly tapered diameter. The latter is demonstrated to possess a smooth variation in diameter along the length of the capillary (tunable with the micromachining trajectories). This would lead to a longitudinal plasma density gradient in the waveguide that may dramatically improve the laser-plasma interaction efficiency in applications

Challenges of dosimetry of ultra-short pulsed very high energy electron beams

Very high energy electrons (VHEE) in the range from 100–250 MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetric properties compared with 6-20 MV photons generated by clinical linear accelerators (LINACs). VHEE beams have characteristics unlike any other beams currently used for radiotherapy: femtosecond to picosecond duration electron bunches, which leads to very high dose per pulse, and energies that exceed that currently used in clinical applications. Dosimetry with conventional online detectors, such as ionization chambers or diodes, is a challenge due to non-negligible ion recombination effects taking place in the sensitive volumes of these detectors. FLUKA and Geant4 Monet Carlo (MC) codes have been employed to study the temporal and spectral evolution of ultrashort VHEE beams in a water phantom. These results are complemented by ion recombination measurements employing an IBA CC04 ionization chamber for a 165 MeV VHEE beam. For comparison, ion recombination has also been measured using the same chamber with a conventional 20 MeV electron beam. This work demonstrates that the IBA CC04 ionization chamber exhibits significant ion recombination and is therefore not suitable for dosimetry of ultrashort pulsed VHEE beams applying conventional correction factors. Further study is required to investigate the applicability of ion chambers in VHEE dosimetry

Characterization of laser-driven single and double electron bunches with a permanent magnet quadrupole triplet and pepper-pot mask

Electron beams from laser-plasma wakefield accelerators have low transverse emittance, comparable to those from conventional radio frequency accelerators, which highlights their potential for applications, many of which will require the use of quadrupole magnets for optimal electron beam transport. We report on characterizing electron bunches where double bunches are observed under certain conditions. In particular, we present pepper-pot measurements of the transverse emittance of 120-200 MeV laser wakefield electron bunches after propagation through a triplet of permanent quadrupole magnets. It is shown that the normalized emittance at source can be as low as 1 π mm mrad (resolution limited), growing by about five times after propagation through the quadrupoles due to beam energy spread. The inherent energy-dependence of the magnets also enables detection of double electron bunches that could otherwise remain unresolved, providing insight into the self-injection of multiple bunches. The combination of quadrupoles and pepper-pot, in addition, acts as a diagnostic for the alignment of the magnetic triplet

Tapered capillaries applied in laser wakefield acceleration

This paper presents realisation of linearly tapered capillary discharge waveguides (CDWs), manufactured using a femtosecond laser micromachining technique. Waveguiding of a low power, 50 fs duration laser pulse is demonstrated and, despite a slight mismatch of the laser focal spot size with respect to the capillary entrance size, efficient guiding of the Gaussian-shaped laser pulse is obtained. Energy transmission of 80% is obtained for optimal delay of the laser pulse arrival time with respect to the discharge current pulse

Defining robustness protocols: a method to include and evaluate robustness in clinical plans.

This is the final version of the article. It first appeared from IOP Publishing via http://dx.doi.org/10.1088/0031-9155/60/7/2671We aim to define a site-specific robustness protocol to be used during the clinical plan evaluation process. Plan robustness of 16 skull base IMPT plans to systematic range and random set-up errors have been retrospectively and systematically analysed. This was determined by calculating the error-bar dose distribution (ebDD) for all the plans and by defining some metrics used to define protocols aiding the plan assessment. Additionally, an example of how to clinically use the defined robustness database is given whereby a plan with sub-optimal brainstem robustness was identified. The advantage of using different beam arrangements to improve the plan robustness was analysed. Using the ebDD it was found range errors had a smaller effect on dose distribution than the corresponding set-up error in a single fraction, and that organs at risk were most robust to the range errors, whereas the target was more robust to set-up errors. A database was created to aid planners in terms of plan robustness aims in these volumes. This resulted in the definition of site-specific robustness protocols. The use of robustness constraints allowed for the identification of a specific patient that may have benefited from a treatment of greater individuality. A new beam arrangement showed to be preferential when balancing conformality and robustness for this case. The ebDD and error-bar volume histogram proved effective in analysing plan robustness. The process of retrospective analysis could be used to establish site-specific robustness planning protocols in proton therapy. These protocols allow the planner to determine plans that, although delivering a dosimetrically adequate dose distribution, have resulted in sub-optimal robustness to these uncertainties. For these cases the use of different beam start conditions may improve the plan robustness to set-up and range uncertainties.This work was partly funded by an MRC Doctoral Training Grant

Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets

Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory process. That the latter could contribute to β-cell hyperactivity/proliferation and possibly lead to progressive β-cell failure in these animals, deserves further investigations

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

understanding and control of ultrsfast currents for terahertz generation

Development of terahertz pulse sources and methods are ongoing with an urge to reduce cost, increase quality of emitter design and improve on the output power. This thesis details two advances made in creating terahertz pulses from ultrafast currents, the first is optimising the biasing method used on photoconductive antennas for terahertz emission and the second manufacturing and studying electronemission type terahertz emitters.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Terahertz-pulse emission through laser excitation of surface plasmons in a metal grating

The second-order processes of optical-rectification and photoconduction are well known and widely used to produce ultrafast electromagnetic pulses in the terahertz frequency domain. We present a new form of rectification that relies on the excitation of surface plasmons in metal films deposited on a shallow grating. Multiphoton ionization and ponderomotive acceleration of electrons in the enhanced evanescent field of the surface plasmons results in a femtosecond current surge and emission of terahertz electromagnetic radiation. Using gold, this rectification process is third or higher-order in the incident field

Alternating high-voltage biasing for terahertz large-area photoconductive emitters

High-voltage biasing is necessary for efficient generation of terahertz radiation using large-area photoconductive emitters and for electric-field-oriented charge-transfer studies. Coherent detection of terahertz pulses allows ac biasing to be the basis of modulation for lock-in detection. Biasing emitters with an ac field also removes the need for a complete conduction path. The experimental advantages of this approach along with a simple resonant method of generating the high-voltage bias applicable to higher-repetition-rate (up to a few hundred kilohertz) regeneratively amplified systems are described. (c) 2006 American Institute of Physics