A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer.

Background: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2'-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.

Methods: Patients progressing 6-12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) on day 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.

Results: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatin hypersensitivity (47% vs 21%).

Conclusions: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents should be considered in future combination studies.

Classical and quantum aspects of multimode parametric interactions

Parametric interactions in nonlinear crystals represent a powerful tool in the optical manipulation of information, both in the classical and the quantum regime. Here, we analyze in detail classical and quantum aspects of three-and five-mode parametric interactions in chi(2) nonlinear crystals. The equations of motion are explicitly derived and then solved within the parametric approximation. We describe several applications, including holography, all-optical gates, generation of entanglement, and telecloning. Experimental results on the photon distributions and correlations of the generated beams are also reported and discussed.

Instrumentation for diagnostics and control of laser-accelerated proton (ion) beams

Suitable instrumentation for laser-accelerated proton (ion) beams is critical for development of integrated, laser-driven ion accelerator systems. Instrumentation aimed at beam diagnostics and control must be applied to the driving laser pulse, the laser-plasma that forms at the target and the emergent proton (ion) bunch in a correlated way to develop these novel accelerators. This report is a brief overview of established diagnostic techniques and new developments based on material presented at the first workshop on 'Instrumentation for Diagnostics and Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson spectrometers, prompt inline scintillators, time and space-resolved interferometry (TASRI) and nuclear activation schemes. Repetition-rated instrumentation requirements for target metrology are also addressed. (C) 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Hybrid address spaces: A methodology for implementing scalable high-level programming models on non-coherent many-core architectures

This paper introduces hybrid address spaces as a fundamental design methodology for implementing scalable runtime systems on many-core architectures without hardware support for cache coherence. We use hybrid address spaces for an implementation of MapReduce, a programming model for large-scale data processing, and the implementation of a remote memory access (RMA) model. Both implementations are available on the Intel SCC and are portable to similar architectures. We present the design and implementation of HyMR, a MapReduce runtime system whereby different stages and the synchronization operations between them alternate between a distributed memory address space and a shared memory address space, to improve performance and scalability. We compare HyMR to a reference implementation and we find that HyMR improves performance by a factor of 1.71× over a set of representative MapReduce benchmarks. We also compare HyMR with Phoenix++, a state-of-art implementation for systems with hardware-managed cache coherence in terms of scalability and sustained to peak data processing bandwidth, where HyMR demon- strates improvements of a factor of 3.1× and 3.2× respectively. We further evaluate our hybrid remote memory access (HyRMA) programming model and assess its performance to be superior of that of message passing.

Dependence of laser-driven coherent synchrotron emission efficiency on pulse ellipticity and implications for polarization gating

The polarization dependence of laser-driven coherent synchrotron emission transmitted through thin foils is investigated experimentally. The harmonic generation process is seen to be almost completely suppressed for circular polarization opening up the possibility of producing isolated attosecond pulses via polarization gating. Particle-in-cell simulations suggest that current laser pulses are capable of generating isolated attosecond pulses with high pulse energies.

Design of a compact spectrometer for high-flux MeV gamma-ray beams

A novel design for a compact gamma-ray spectrometer is presented. The proposed system allows for spectroscopy of high-flux multi-MeV gamma-ray beams with MeV energy resolution in a compact design. In its basic configuration, the spectrometer exploits conversion of gamma-rays into electrons via Compton scattering in a low-Z material. The scattered electron population is then spectrally resolved using a magnetic spectrometer. The detector is shown to be effective for gamma-ray energies between 3 and 20 MeV. The main properties of the spectrometer are confirmed by Monte Carlo simulations.

Measurements of high-energy radiation generation from laser-wakefield accelerated electron beams

Using high-energy (∼0.5 GeV) electron beams generated by laser wakefield acceleration (LWFA), bremsstrahlung radiation was created by interacting these beams with various solid targets. Secondary processes generate high-energy electrons, positrons, and neutrons, which can be measured shot-to-shot using magnetic spectrometers, short half-life activation, and Compton scattering. Presented here are proof-of-principle results from a high-resolution, high-energy gamma-ray spectrometer capable of single-shot operation, and high repetition rate activation diagnostics. We describe the techniques used in these measurements and their potential applications in diagnosing LWFA electron beams and measuring high-energy radiation from laser-plasma interactions.

Influence of micro and macro cracks due to sustained loading on chloride-induced corrosion of reinforced concrete beams

Chloride-induced corrosion of steel is one of the most commonly found problems affecting the durability of reinforced concrete structures in both marine environment and where de-icing salt is used in winter. As the significance of micro-cracks on chloride induced corrosion is not well documented, 24 reinforced concrete beams (4 different mixes - one containing Portland cement and another containing 35% ground granulated blastfurnace slag at 0.45 and 0.65 water-binder ratios) were subjected to three levels of sustained lateral loading (0%, 50% and 100% of the load that can induce 0.1 mm wide cracks on the tension surface of beam - F_0.1) in this work. The beams were then subjected to weekly cycles of wetting with 10% NaCl solution for 1 day followed by 6 days of drying at 20 (±1) °C up to an exposure period of 60 weeks. The progress of corrosion of steel was monitored using half-cell potential apparatus and linear polarisation resistance (LPR) test. These results have shown that macro-cracks (at load F_0.1) and micro-cracks (at 50% of F_0.1) greatly accelerated both the initiation and propagation stages of the corrosion of steel in the concrete beams. Lager crack widths for the F_0.1 load cases caused higher corrosion rates initially, but after about 38 weeks of exposure, there was a decrease in the rate of corrosion. However, such trends could not be found in 50% F _0.1 group of beams. The extent of chloride ingress also was influenced by the load level. These findings suggest that the effect of micro-cracking at lower loads are very important for deciding the service life of reinforced concrete structures in chloride exposure environments. © 2014 4th International Conference on the Durability of Concrete Structures.

Post-tensioning glulam timber beams with basalt FRP tendons

Improvements in the structural performance of glulam timber beams by the inclusion of reinforcing materials can increase both the service performance and ultimate capacity. This paper describes a series of four-point bending tests conducted, under service loads and to failure, on unreinforced, reinforced and post-tensioned glulam timber beams, where the reinforcing tendon used is 12 mm dia. basalt fibre-reinforced polymer. The research is designed to evaluate the benefits offered by including an active reinforcement in contrast to the passive reinforcement typically used within timber strengthening works, in addition to establishing the effect that bonding the reinforcing tendon has on the material's performance. Further experimental tests have also been developed to investigate the long-term implications of this research, with emphasis placed upon creep and loss of post-tensioning; however, this is ongoing and is not presented in this paper. The laboratory investigations establish that the flexural strength and stiffness increase for both the unbonded and bonded post-tensioned timbers compared to the unreinforced and reinforced beams. Timber that is post-tensioned with an unbonded basalt fibre-reinforced polymer tendon shows a flexural strength increase of 2ṡ8% and an increase in stiffness of 8ṡ7%. Post-tensioned beams with a bonded basalt fibre-reinforced polymer tendon show increases in flexural strength and stiffness of 15ṡ4% and 11ṡ5% respectively.

POST-TENSIONING OF TIMBER BEAMS WITH BASALT FIBRE REINFORCED POLYMER

Improvements in the structural performance of glulam timber beams by the inclusion of reinforcing materials can improve both the service performance and ultimate capacity. In recent years research focusing on the addition of fibre reinforced polymers to strengthen members has yielded positive results. However, the FRP material is still a relatively expensive material and its full potential has not been realised in combination with structural timber. This paper describes a series of four-point bending tests that were conducted, under service and ultimate loads, on post-tensioned glulam timber beams where the reinforcing tendon used was 12 mm diameter Basalt Fibre Reinforced Polymer (BFRP). The research was designed to evaluate the additional benefits of including an active type of reinforcement, by post-tensioning the BFRP tendon, as opposed to the passive approach of simply reinforcing the timber beam.
From the laboratory investigations, it was established that there was a 16% increase in load carrying capacity, in addition to a 14% reduction in deflection under service loads when members containing the post-tensioned BFRP composite are compared with control timber specimens. Additionally a more favourable ductile failure mode was witnessed compared to the brittle failure of an unreinforced timber beam. The results support the assumption that by initially stressing the embedded FRP tendon the structural benefits experienced by the timber member increase in a number of ways, indicating that there is significant scope for this approach in practical applications.

Ultrahigh Brilliance Multi-MeV γ-Ray Beams from Nonlinear Relativistic Thomson Scattering

We report on the generation of a narrow divergence (θγ<2.5mrad), multi-MeV (Emax≈18MeV) and ultrahigh peak brilliance (>1.8×1020photonss-1mm-2mrad-2 0.1% BW) γ-ray beam from the scattering of an ultrarelativistic laser-wakefield accelerated electron beam in the field of a relativistically intense laser (dimensionless amplitude a0≈2). The spectrum of the generated γ-ray beam is measured, with MeV resolution, seamlessly from 6 to 18 MeV, giving clear evidence of the onset of nonlinear relativistic Thomson scattering. To the best of our knowledge, this photon source has the highest peak brilliance in the multi-MeV regime ever reported in the literature.

Laser-driven generation of high-quality ultra-relativistic positron beams

An ultra-relativistic electron beam propagating through a high-Z solid triggersan electromagnetic cascade, whereby a large number of high-energy photons andelectron–positron pairs are produced mainly via the bremsstrahlung and Bethe–Heitler processes, respectively. These mechanisms are routinely used to generatepositron beams in conventional accelerators such as the electron–positron collider(LEP). Here we show that the application of similar physical mechanisms to a laserdrivenelectron source allows for the generation of high-quality positron beams in amuch more compact and cheaper configuration. We anticipate that the applicationof these results to the next generation of lasers might open the pathway for therealization of an all-optical high-energy electron–positron collider.