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1.
Phys Rev Lett ; 119(5): 054801, 2017 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-28949740

RESUMO

The acceleration of ions from ultrathin (10-100 nm) carbon foils has been investigated using intense (∼6×10^{20} W cm^{-2}) ultrashort (45 fs) laser pulses, highlighting a strong dependence of the ion beam parameters on the laser polarization, with circularly polarized (CP) pulses producing the highest energies for both protons and carbons (25-30 MeV/nucleon); in particular, carbon ion energies obtained employing CP pulses were significantly higher (∼2.5 times) than for irradiations employing linearly polarized pulses. Particle-in-cell simulations indicate that radiation pressure acceleration becomes the dominant mechanism for the thinnest targets and CP pulses.

2.
Opt Express ; 24(24): 28104-28112, 2016 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-27906375

RESUMO

A significant level of back reflected laser energy was measured during the interaction of ultra-short, high contrast PW laser pulses with solid targets at 30° incidence. 2D PIC simulations carried out for the experimental conditions show that at the laser-target interface a dynamic regular structure is generated during the interaction, which acts as a grating (quasi-grating) and reflects back a significant amount of incident laser energy. With increasing laser intensity above 1018 W/cm2 the back reflected fraction increases due to the growth of the surface modulation to larger amplitudes. Above 1020 W/cm2 this increase results in the partial destruction of the quasi-grating structure and, hence, in the saturation of the back reflection efficiency. The PIC simulation results are in good agreement with the experimental findings, and, additionally, demonstrate that in presence of a small amount of pre-plasma this regular structure will be smeared out and the back reflection reduced.

3.
Epigenetics ; 18(1): 2216005, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37246786

RESUMO

While epigenetic mechanisms such as DNA methylation and histone modification are known to be important for gene suppression, relatively little is still understood about the interplay between these systems. The UHRF1 protein can interact with both DNA methylation and repressive chromatin marks, but its primary function in humans has been unclear. To determine what that was, we first established stable UHRF1 knockdowns (KD) in normal, immortalized human fibroblasts using targeting shRNA, since CRISPR knockouts (KO) were lethal. Although these showed a loss of DNA methylation across the whole genome, transcriptional changes were dominated by the activation of genes involved in innate immune signalling, consistent with the presence of viral RNA from retrotransposable elements (REs). We confirmed using mechanistic approaches that 1) REs were demethylated and transcriptionally activated; 2) this was accompanied by activation of interferons and interferon-stimulated genes and 3) the pathway was conserved across other adult cell types. Restoring UHRF1 in either transient or stable KD systems could abrogate RE reactivation and the interferon response. Notably, UHRF1 itself could also re-impose RE suppression independent of DNA methylation, but not if the protein contained point mutations affecting histone 3 with trimethylated lysine 9 (H3K9me3) binding. Our results therefore show for the first time that UHRF1 can act as a key regulator of retrotransposon silencing independent of DNA methylation.


Assuntos
Metilação de DNA , RNA Viral , Humanos , RNA Viral/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Imunidade Inata/genética , Interferons/metabolismo
4.
Rev Sci Instrum ; 93(5): 053303, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35649771

RESUMO

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

5.
Sci Rep ; 9(1): 4471, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-30872656

RESUMO

Protontherapy has emerged as more effective in the treatment of certain tumors than photon based therapies. However, significant capital and operational costs make protontherapy less accessible. This has stimulated interest in alternative proton delivery approaches, and in this context the use of laser-based technologies for the generation of ultra-high dose rate ion beams has been proposed as a prospective route. A better understanding of the radiobiological effects at ultra-high dose-rates is important for any future clinical adoption of this technology. In this study, we irradiated human skin fibroblasts-AG01522B cells with laser-accelerated protons at a dose rate of 109 Gy/s, generated using the Gemini laser system at the Rutherford Appleton Laboratory, UK. We studied DNA double strand break (DSB) repair kinetics using the p53 binding protein-1(53BP1) foci formation assay and observed a close similarity in the 53BP1 foci repair kinetics in the cells irradiated with 225 kVp X-rays and ultra- high dose rate protons for the initial time points. At the microdosimetric scale, foci per cell per track values showed a good correlation between the laser and cyclotron-accelerated protons indicating similarity in the DNA DSB induction and repair, independent of the time duration over which the dose was delivered.


Assuntos
Quebras de DNA de Cadeia Dupla , Fibroblastos/efeitos da radiação , Terapia com Prótons/instrumentação , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular , Ciclotrons/instrumentação , Relação Dose-Resposta à Radiação , Fibroblastos/química , Fibroblastos/citologia , Humanos , Lasers , Estudos Prospectivos , Terapia com Prótons/efeitos adversos
6.
Sci Rep ; 7(1): 2152, 2017 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-28526837

RESUMO

We present the characteristics of track formation on the front and rear surfaces of CR-39 produced by laser-driven protons and carbon ions. A methodological approach, based on bulk etch length, is proposed to uniquely characterize the particle tracks in CR-39, enabling comparative description of the track characteristics in different experiments. The response of CR-39 to ions is studied based on the energy dependent growth rate of the track diameter to understand the intrinsic particle stopping process within the material. A large non-uniformity in the track diameter is observed for CR-39 with thickness matching with the stopping range of particles. Simulation and experimental results show the imprint of longitudinal range straggling for energetic protons. Moreover, by exploiting the energy dependence of the track diameter, the energy resolution (δE/E) of CR-39 for few MeV protons and Carbon ion is found to be about 3%.

7.
Rev Sci Instrum ; 87(8): 083301, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27587107

RESUMO

The absolute calibration of a microchannel plate (MCP) assembly using a Thomson spectrometer for laser-driven ion beams is described. In order to obtain the response of the whole detection system to the particles' impact, a slotted solid state nuclear track detector (CR-39) was installed in front of the MCP to record the ions simultaneously on both detectors. The response of the MCP (counts/particles) was measured for 5-58 MeV carbon ions and for protons in the energy range 2-17.3 MeV. The response of the MCP detector is non-trivial when the stopping range of particles becomes larger than the thickness of the detector. Protons with energies E ≳ 10 MeV are energetic enough that they can pass through the MCP detector. Quantitative analysis of the pits formed in CR-39 and the signal generated in the MCP allowed to determine the MCP response to particles in this energy range. Moreover, a theoretical model allows to predict the response of MCP at even higher proton energies. This suggests that in this regime the MCP response is a slowly decreasing function of energy, consistently with the decrease of the deposited energy. These calibration data will enable particle spectra to be obtained in absolute terms over a broad energy range.

8.
Rev Sci Instrum ; 86(12): 123302, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26724017

RESUMO

The paper presents the calibration of Fuji BAS-TR image plate (IP) response to high energy carbon ions of different charge states by employing an intense laser-driven ion source, which allowed access to carbon energies up to 270 MeV. The calibration method consists of employing a Thomson parabola spectrometer to separate and spectrally resolve different ion species, and a slotted CR-39 solid state detector overlayed onto an image plate for an absolute calibration of the IP signal. An empirical response function was obtained which can be reasonably extrapolated to higher ion energies. The experimental data also show that the IP response is independent of ion charge states.

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