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We present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic "contact-first" model where DSB are considered immobile. Here we apply this clustering model to evaluate the number of remaining RIF over time. We also show that the newly introduced kinetic metrics can be used as surrogate biomarkers for in vivo radiation toxicity, with potential applications in radiotherapy and human space exploration. In particular, we observed an association between the characteristic time constant of RIF repair measured in vitro and survival levels of immune cells collected from irradiated mice. Moreover, the speed of DNA damage repair correlated not only with radiation-induced cellular survival in vivo, but also with spontaneous cancer incidence data collected from the Mouse Tumor Biology database, suggesting a relationship between the efficiency of DSB repair after irradiation and cancer risk.To better predict clinical outcome after radiation exposure, it is very important to know the absorbed dose and body areas exposed. Previously we found that 22 miRNAs appeared to predict total- and partial-body irradiation (TBI and PBI, respectively) patterns and were suggestive of the percentage of the body exposed in a baboon model. Motivated by these results, we performed a similar analysis on the transcriptional level (mRNAs) using whole genome microarrays. Brimarafenib From 17 irradiated baboons, blood samples were taken before, and at 1, 2, 7, 28 and 75-106 days postirradiation to an equivalent TBI dose of 2.5 or 5 Gy applied either to the total body or to different parts of the body such as the upper body (UBE) or left hemibody (LHB). We compared quantile normalized log2-transformed gene expression values with three exposure pattern comparisons, namely TBI vs. PBI, TBI vs. LHB and UBE vs. LHB using Kruskal-Wallis and logistic regression analysis for receiver-operator characteristic (ROC) calculation. We found severtime frame (2-75 days postirradiation) than miRNA, but due to the transient gene expression changes a different set of candidate mRNAs appears to be required at each day after irradiation.In this work, we investigated the delivery of a clinically acceptable pediatric whole brain radiotherapy plan at FLASH dose rates using two lateral opposing 40-MeV electron beams produced by a practically realizable linear accelerator system. The EGSnrc Monte Carlo software modules, BEAMnrc and DOSXYZnrc, were used to generate whole brain radiotherapy plans for a pediatric patient using two lateral opposing 40-MeV electron beams. Electron beam phase space files were simulated using a model of a diverging beam with a diameter of 10 cm at 50 cm SAD (defined at brain midline). The electron beams were collimated using a 10-cm-thick block composed of 5 cm of aluminum oxide and 5 cm of tungsten. For comparison, a 6-MV photon plan was calculated with the Varian AAA algorithm. Electron beam parameters were based on a novel linear accelerator designed for the PHASER system and powered by a commercial 6-MW klystron. Calculations of the linear accelerator's performance indicated an average beam current of at least 6.25 µA, providing a dose rate of 115 Gy/s at isocenter, high enough for cognition-sparing FLASH effects. The electron plan was less homogenous with a homogeneity index of 0.133 compared to the photon plan's index of 0.087. Overall, the dosimetric characteristics of the 40-MeV electron plan were suitable for treatment. In conclusion, Monte Carlo simulations performed in this work indicate that two lateral opposing 40-MeV electron beams can be used for pediatric whole brain irradiation at FLASH dose rates of >115 Gy/s and serve as motivation for a practical clinical FLASH radiotherapy system, which can be implemented in the near future.
The Food Safety Modernization Act, specifically the Produce Safety Rule, requires growers to clean and sanitize food contact surfaces to protect against produce contamination. An ATP monitoring device is a potential sanitation tool to monitor the efficacy of an on-farm cleaning and sanitation program that could help growers meet regulatory expectations mandated by the Produce Safety Rule. This ATP monitoring device uses bioluminescence to detect all ATP (found in bacteria and produce matter cells) from a swabbed surface. Because little work has been done to test the efficacy of these tools under postharvest conditions, the present study evaluated ATP measurement for postharvest food contact surface cleanliness evaluation. Concentrations of leafy greens (spinach, romaine, and red cabbage, with or without Listeria innocua) were used as organic matter applied to stainless steel, high-density polyethylene plastic, and bamboo wood coupons to represent postharvest food contact surfaces. The ATP levels on the coupaces; however, it is not recommended for wood surfaces.
This study evaluated the efficacy of copper alloy surfaces for inactivation of Tulane virus (TV), assessed by plaque assay and porcine gastric mucin-conjugated magnetic bead (PGM-MB) binding assay, followed by quantitative reverse transcription PCR (PGM-MB-RT-qPCR assay). In addition, the efficacy of a copper surface for inactivation of human norovirus (HuNoV) GII.4 Sydney and GI.3B Potsdam strains was evaluated by PGM-MB-RT-qPCR assay. Results of time-dependent inactivation of viruses on copper, bronze, and brass coupons revealed that 15 min of surface treatments of each of the copper and copper alloys achieved >4-log reduction of purified TV, as assessed by plaque assay, while up to 20 min of copper alloy surface treatments only achieved ∼2-log reduction, as assessed by PGM-MB-RT-qPCR assay. As assessed by PGM-MB-RT-qPCR assay, 10 min of copper surface treatments achieved reductions of 3 and 4 log units for HuNoVs GII.4 Sydney and GI.3B Potsdam, respectively. Results from this study suggest that even though PGM-MB-RT-qPCR assay underestimated the efficacy of copper alloy surface inactivation of TV, copper alloy surfaces were able to effectively inactivate TV and HuNoVs.