Mapping the Sensitive Volume of an Ion-Counting Nanodosimeter

We present two methods of independently mapping the dimensions of the sensitive volume in an ion-counting nanodosimeter. The first method is based on a calculational approach simulating the extraction of ions from the sensitive volume, and the second method on probing the sensitive volume with 250 MeV protons. Sensitive-volume maps obtained with both methods are compared and systematic errors inherent in both methods are quantified.Comment: 27 pages, 8 figures. Submitted to JINST, Jan. 16 200

Genetic analysis reveals different roles of Schizosaccharomyces pombe sfr1

DNA double-strand break (DSB) repair mediated by the Rad51 pathway of homologous recombination is conserved in eukaryotes. In yeast, Rad51 paralogs, Saccharomyces cerevisiae Rad55-Rad57 and Schizosaccharomyces pombe Rhp55-Rhp57, are mediators of Rad51 nucleoprotein formation. The recently discovered S. pombe Sfr1/Dds20 protein has been shown to interact with Rad51 and to operate in the Rad51-dependent DSB repair pathway in parallel to the paralog-mediated pathway. Here we show that Sfr1 is a nuclear protein and acts downstream of Rad50 in DSB processing. sfr1Δ is epistatic to rad18 − and rad60 −, and Sfr1 is a high-copy suppressor of the replication and repair defects of a rad60 mutant. Sfr1 functions in a Cds1-independent UV damage tolerance mechanism. In contrast to mitotic recombination, meiotic recombination is significantly reduced in sfr1Δ strains. Our data indicate that Sfr1 acts in DSB repair mainly outside of S-phase, and is required for wild-type levels of meiotic recombination. We suggest that Sfr1 acts early in recombination and has a specific role in Rad51 filament assembly, distinct from that of the Rad51 paralog

A novel approach to study radiation track structure with nanometer-equivalent resolution

Clustered DNA damages are considered the critical lesions in the pathways leading from the initial energy deposition by radiation to radiobiological damage. The spatial distribution of the initial DNA damage is mainly determined by radiation track-structure at the nanometer level. In this work, a novel experimental approach to image the three-dimensional structure of micrometric radiation track segments is presented. The approach utilizes the detection of single ions created in low-pressure gas. Ions produced by radiation drift towards a GEM-like 2D hole-pattern detector. When entering individual holes, ions can induce ion-impact ionization of the working-gas starting a confined electron avalanche that generates the output signal. By registering positive ions rather than electrons, diffusion is reduced and a spatial resolution of the track image of the order of water-equivalent nanometers can be achieved. Measurements and simulations to characterize the performance of a few detector designs were performed. Different cathode materials were tested and ionization cluster size distributions of 241Am alpha particles were measured. The electric field configuration in the detector was calculated to optimize the ion focusing into the detector holes. The preliminary results obtained show the directions for further development of the detector

A Scintillator Beam Monitor for Real-Time FLASH Radiotherapy

FLASH Radiotherapy (RT) is a potentially new cancer radiotherapy technique where an entire therapeutic dose is delivered in about 0.1 s and at ~1000 times higher dose rate than in conventional RT. For clinical trials to be conducted safely, precise and fast beam monitoring that can generate an out-of-tolerance beam interrupt is required. A FLASH Beam Scintillator Monitor (FBSM) is being developed based in part on two novel proprietary scintillator materials: an organic polymeric material (PM) and inorganic hybrid (HM). The FBSM provides large area coverage, low mass profile, linear response over a broad dynamic range, radiation tolerance, and real-time analysis IEC-compliant fast beam-interrupt signal. This paper includes the design concept and test results from prototype devices in radiation beams that include heavy ions, low energy protons at nA currents, FLASH level dose per pulse electron beams, and in a hospital radiotherapy clinic with electron beams. Results include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. PM and HM scintillator exhibited no measurable drop in signal after a cumulative dose of 9 kGy and 20 kGy respectively. HM showed a small -0.02%/kGy signal decrease after a 212 kGy cumulative dose resulting from continuous exposure for 15 minutes at a high FLASH dose rate of 234 Gy/s. These tests established the linear response of the FBSM with respect to beam currents, dose per pulse, and material thickness. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. At 20 kfps or 50 microsec/frame, the real-time FPGA based computation and analysis of beam position, beam shape, and beam dose takes < 1 microsec.Comment: 15 pages, 9 figure

A scintillating bolometer for experiments on double beta decay

Abstract The scintillation yields of CaF 2 crystals with different doping concentration of Europium have been measured at low temperatures and their bolometric behavior has been investigated. After these studies we have constructed the first "scintillating bolometer" where the heat and scintillation pulses produced by charged particles are simultaneously recorded. With this method a strong suppression of the background from α -particles in the energy region of interest for searches on double beta decay of 48 Ca can be achieved

A truncated DNA-damage-signaling response is activated after DSB formation in the G1 phase of Saccharomyces cerevisiae

In Saccharomyces cerevisiae, the DNA damage response (DDR) is activated by the spatio-temporal colocalization of Mec1-Ddc2 kinase and the 9-1-1 clamp. In the absence of direct means to monitor Mec1 kinase activation in vivo, activation of the checkpoint kinase Rad53 has been taken as a proxy for DDR activation. Here, we identify serine 378 of the Rad55 recombination protein as a direct target site of Mec1. Rad55-S378 phosphorylation leads to an electrophoretic mobility shift of the protein and acts as a sentinel for Mec1 activation in vivo. A single double-stranded break (DSB) in G1-arrested cells causes phosphorylation of Rad55-S378, indicating activation of Mec1 kinase. However, Rad53 kinase is not detectably activated under these conditions. This response required Mec1-Ddc2 and loading of the 9-1-1 clamp by Rad24-RFC, but not Rad9 or Mrc1. In addition to Rad55–S378, two additional direct Mec1 kinase targets are phosphorylated, the middle subunit of the ssDNA-binding protein RPA, RPA2 and histone H2A (H2AX). These data suggest the existence of a truncated signaling pathway in response to a single DSB in G1-arrested cells that activates Mec1 without eliciting a full DDR involving the entire signaling pathway including the effector kinases

A Highly Accelerated Parallel Multi-GPU based Reconstruction Algorithm for Generating Accurate Relative Stopping Powers

Low-dose Proton Computed Tomography (pCT) is an evolving imaging modality that is used in proton therapy planning which addresses the range uncertainty problem. The goal of pCT is generating a 3D map of Relative Stopping Power (RSP) measurements with high accuracy within clinically required time frames. Generating accurate RSP values within the shortest amount of time is considered a key goal when developing a pCT software. The existing pCT softwares have successfully met this time frame and even succeeded this time goal, but requiring clusters with hundreds of processors. This paper describes a novel reconstruction technique using two Graphics Processing Unit (GPU) cores, such as is available on a single Nvidia P100. The proposed reconstruction technique is tested on both simulated and experimental datasets and on two different systems namely Nvidia K40 and P100 GPUs from IBM and Cray. The experimental results demonstrate that our proposed reconstruction method meets both the timing and accuracy with the benefit of having reasonable cost, and efficient use of power.Comment: IEEE NSS/MIC 201

The Particle Tracking Silicon Microscope PTSM

Abstract-A novel position-and energy-sensitive particle detector for radiobiological application is described. The aim is to support research in radiation response of biological systems, for example in the induction of mutations in C. elegans, where precise knowledge of location and intensity of the radiation is crucial to understand radiation sensitivity of individual cells. The &quot;Particle Tracking Silicon Microscope&quot; (PTSM) consists of a silicon strip detector in direct contact with radiobiological samples (e.g., C. elegans), such that the location and intensity of particle radiation can be controlled at the 10µm scale. The readout is performed with low-noise readout electronics, which allows the determination of the particle&apos;s position from the hit strip address and its energy from the specific energy loss. In our implementation, the energy loss is measured through the timeover-threshold (TOT). The noise rate at acceptable thresholds is so low that the single particles can be detected with 100% efficiency. The performance of the front-end ASIC is described, and the results of initial environmental tests are reported. These include placing biological samples and saline solutions in direct contact with the silicon detectors