High LET Research Articles

Organic Scintillator-Fibre Sensors for Proton Therapy Dosimetry: SCSF-3HF and EJ-260

In proton therapy, the dose from secondary neutrons to the patient can contribute to side effects and the creation of secondary cancer. A simple and fast detection system to distinguish between dose from protons and neutrons both in pretreatment verification as well as potentially in vivo monitoring is needed to minimize dose from secondary neutrons. Two 3 mm long, 1 mm diameter organic scintillators were tested for candidacy to be used in a proton–neutron discrimination detector. The SCSF-3HF (1500) scintillating fibre (Kuraray Co. Chiyoda-ku, Tokyo, Japan) and EJ-260 plastic scintillator (Eljen Technology, Sweetwater, TX, USA) were irradiated at the TRIUMF Neutron Facility and the Proton Therapy Research Centre. In the proton beam, we compared the raw Bragg peak and spread-out Bragg peak response to the industry standard Markus chamber detector. Both scintillator sensors exhibited quenching at high LET in the Bragg peak, presenting a peak-to-entrance ratio of 2.59 for the EJ-260 and 2.63 for the SCSF-3HF fibre, compared to 3.70 for the Markus chamber. The SCSF-3HF sensor demonstrated 1.3 times the sensitivity to protons and 3 times the sensitivity to neutrons as compared to the EJ-260 sensor. Combined with our equations relating neutron and proton contributions to dose during proton irradiations, and the application of Birks’ quenching correction, these fibres provide valid candidates for inexpensive and replicable proton-neutron discrimination detectors.

Repair Kinetics of DSB-Foci Induced by Proton and α-Particle Microbeams of Different Energies.

In this work, the induction and repair of radiation-induced 53BP1 foci were studied in human umbilical vein endothelial cells irradiated at the PTB microbeam with protons and α-particles of different energies. The data were analyzed in terms of the mean number of 53BP1 foci induced by the different ion beams. The number of 53BP1 foci found at different times post-irradiation suggests that the disappearance of foci follows first order kinetics. The mean number of initially produced foci shows the expected increase with LET. The most interesting finding of this work is that the absolute number of persistent foci increases with LET but not their fraction. Furthermore, protons seem to produce more persistent foci as compared to α-particles of even higher LET. This may be seen as experimental evidence that protons may be more effective in producing severe DNA lesions, as was already shown in other work, and that LET may not be the best suited parameter to characterize radiation quality.

Radioprotective Effect of Nanocerium by Irradiation of Mice with Carbon Ions in Medium and Lethal Doses.

The data of the study of the radioprotective properties of nanocerium (nCeO2) after total irradiation of mice with carbon ions in medium and lethal doses according to the micronucleus test and the criterion of 30-day survival are presented. A significant protective effect of nCeO2 upon irradiation at medium doses was observed at per os administration for 5 days before irradiation (that is, at long-term prophylactic use). Mouse survival data showed no protective effect of per os administration of nCeO2 in contrast to the micronucleus test results. After injections of both nCeO2 and saline solution 24 h before or immediately after irradiation, the radioprotective effect was detected using both methods. The data obtained revealed the dependence of the observed effects on the mode and time of nCeO2 administration, the influence of the solvent, the level of doses and the quality of radiation, as well as demonstrated the possibility of using nanocerium preparations to protect organisms from radiation with high LET values and the importance of further studies of the radioprotective properties of new nanomaterials.

Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated with Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study

<h3>Purpose/Objective(s)</h3> To retrospectively investigate empirical relative biological effectiveness (RBE) for mandible osteoradionecrosis (ORN) in head and neck (H&N) cancer patients treated with pencil-beam-scanning proton therapy (PBSPT). <h3>Materials/Methods</h3> We included 1,266 H&N cancer patients, of which, 931 patients were treated with volumetric-modulated arc therapy (VMAT) and 335 were treated with PBSPT. Among them, 26 VMAT and 9 PBSPT patients experienced mandible ORN (ORN group), while all others were included in the control group. To minimize the impact of the possible imbalance in clinical factors between VMAT and PBSPT patients in the dosimetric comparison between these two modalities and the resulting RBE quantification, we formed a 1:1 case-matched patient cohort (335 VMAT patients and 335 PBSPT patients including both the ORN and control groups) using the greedy nearest neighbor matching of propensity scores. Mandible dosimetric metrics were extracted from the case-matched patient cohort and statistically tested to evaluate the association with mandibular ORN to derive dose volume constraints (DVCs) for VMAT and PBSPT, respectively. We sought the equivalent constraint doses for VMAT so that the critical volumes of VMAT were equal to those of PBSPT at different physical doses. Empirical RBEs of PBSPT for ORN were obtained by calculating the ratio between the derived equivalent constraint doses and physical doses of PBSPT. Bootstrapping was further used to get the confidence intervals. <h3>Results</h3> Clinical variables of age, gender, tumor stage, prescription dose, chemotherapy, hypertension or diabetes, dental extraction, smoking history, or current smoker were not statistically related to the incidence of ORN in the overall patient cohort. Smoking history was found to be significantly associated with the ORN incidence in PBSPT patients only. V40 Gy[RBE], V50 Gy[RBE], and V60 Gy[RBE] were statistically different (<i>p</i> < 0.05) between the ORN and control group for VMAT and PBSPT. Empirical RBEs of 1.58 (95% CI: 1.34-1.64), 1.34 (95% CI: 1.23-1.40), and 1.24 (95% CI: 1.15-1.26) were obtained for proton dose at 40 Gy[RBE=1.1], 50 Gy[RBE = 1.1] and 60 Gy[RBE = 1.1], respectively (Table). <h3>Conclusion</h3> Our study suggested that RBEs were larger than 1.1 at moderate doses (between 40 and 60 Gy[RBE=1.1]) with high LET for mandible ORN. RBEs are underestimated in current clinical practice in PBSPT. The derived DVCs can be used for PBSPT plan evaluation and optimization to minimize the incidence rate of mandible ORN.

PO08: Potential Innovations in Brachytherapy

Optimizing brachytherapy applicability requires circumventing shape size homogeneity limitations as well as allowing concomitant utilization of other modalities especially hyperthermia and nanoparticles. <h3>Material and Methods</h3> For more than a decade, strategies continue to be developed to produce applicators that allow using BTX in clinical situations in which local cancer control is crucial for survival and symptomatic relief. This often involves memory shaped material especially nitinol, novel isotopic states for clinical use and multiple materials. These are to be deployed in naturally occurring or iatrogenic intracavitary sites.. Hyperthermia which has proved effective could be induced multiple ways including adding voltage to the nitinol core, circulating water baths, and externally via ultrasound and radio frequencies. The former allows the hyperthermia applications to be intermittent or continuous although at this time the optimal timing is unknown. In the past quality control of hyperthermia has been a challenge but the use of multiple techniques with feedback can improve hyperthermia homogeneity; as well as the potential use of diffusing nano particles which could incorporate chemotherapy, immunotherapy or even metal particles to generate heat. Continuously emitting radiation sources LDR or vLDR are believed by some investigators to have a biological advantage when compared to HDR based on higher LET and RBE and lower OER; individual clinicians will select the modality for each situation. Because the isotope occupies a much larger volume the Dmax is lower when compared to seeds and efforts are ongoing to further improve the dose gradient.. Since patients with recurrent GBM's have demonstrated short term improvement with both hyperthermia and brachytherapy as with a Gliosite; meeting the challenge of hyperthermia delivery and quality control would be reasonably expect to improve outcomes. In other cancers in which local recurrence/persistence is a clinical issue such a breast cancer and other tumorectomies, bone metastasis, tracheobronchial, gynecological and GI tract warrants further resource utilization. Selective treatment of vascular diseases to prevent restenosis and potentially to improve resect ability in selective sites such as pancreatic cancers may be too provocative. <h3>Results</h3> Multimodality applicator devices have been designed for multiple sites including the brain, bone lesions, GI,thoracic post resection including bi/trifurcating devices as well as multiple patents have been filed and most have already been secured. Monte Carlo calculations have demonstrated feasibility of this strategy. <h3>Conclusion</h3> This work in progress has demonstrated feasibility of using devices that optimize Brachytherapy and offer potential for improved local cancer control in many situations.

S–CO2 heat transfer characteristics analysis in PCHE and vertical channel

Numerical simulations are applied to investigate supercritical carbon dioxide (S–CO2) and heat transfer characteristics in the case of uniform/nonuniform heating conditions in the straight vertical channel and printed circuit heat exchanger (PCHE). The proposed S–CO2 heat transfer correlation agrees well with the experimental values. Results show that high heat flux let S–CO2 heat transfer deterioration likely to occur. Heat transfer deterioration effect will be enhanced as S–CO2 is in area of the gas-like region. Heat transfer enhancement effect will be more significant when S–CO2 is in the area of the liquid-like region. The concept of total length is proposed which is the channel length affected by heat transfer deterioration and entrance effect together. The affected length is 55–70 times of the equivalent diameter in the case of 140 kW/m2 heat flux; the affected length is 85–125 times of the equivalent diameter in the case of 300 kW/m2 heat flux. Changes in dominance of h and λ of PCHE suggest that the convective heat transfer and heat conduction resistance strength of the fluid layer is changing. This study provides guidance for PCHE design and heat transfer enhancement.

Development of a Clinical Neutron Source for Boron Neutron Capture Therapy

<h3>Purpose/Objective(s)</h3> In boron neutron capture therapy (BNCT), a source of epithermal (1 eV to 30 keV) neutrons activates high concentrations of ¹⁰B, selectively accumulated in tumor cells from infusion of a non-radioactive pharmaceutical, whose high LET reaction products fully deposit their energy within 10 microns of the reaction site. Historically, only nuclear reactors provided sufficient neutron intensity and beam quality for clinically acceptable BNCT treatments, but hospital-based BNCT is now feasible using compact accelerator sources. The present work has designed a system to produce an epithermal neutron beam using a tandem electrostatic accelerator, proton beam line, neutron-producing targets, neutron beam shaping assembly (BSA) and collimators. Testing was required to verify that this design can produce a clinically viable neutron source for BNCT in terms of total neutron yield, output reproducibility and operational stability. <h3>Materials/Methods</h3> The present neutron source uses neutrons from the ⁷Li(p,n)⁷Be reaction at nominal proton energy and current of 2.5 MeV and 10 mA. A negative hydrogen ion source is pre-accelerated to 200 keV and injected into the tandem accelerator, which increases the negative ion kinetic energy to half the goal proton energy at its center. A charge exchange target strips the electrons to create positively-charged protons that are further accelerated to the full operational energy at the tandem exit. The proton beam is focused and may be directed to up to three treatment rooms, each with a copper-backed target of natural lithium metal under vacuum. The maximum neutron energy from 2.5 MeV protons slowing down in lithium is 800 keV and requires moderation to the desired epithermal range. A static beam BSA surrounds the target and provides efficient neutron moderation and reflection using carefully chosen materials. The BSA's 25 cm circular exit port may be collimated to small circular epithermal beam diameters as small as 5-8 cm. <h3>Results</h3> A tandem accelerator, proton beam line and lithium target have been installed and began initial testing. Proton energy and current up to 2.3 MeV and 7 mA have been achieved for continuous operating periods exceeding 30 minutes with no energy or current degradation. Raster patterns have been designed to scan the 1-cm diameter proton beam over a 10-cm circular area on the lithium target, and water cooling of the copper backing has maintained maximum target temperatures below 150°C. The measured lithium deposition uniformity is expected to translate to a neutron yield uniformity better than 5%. <h3>Conclusion</h3> This BNCT neutron source has demonstrated operational stability and reproducibility of proton energy, proton current and neutron production. These measurements support an expectation that the equipment currently undergoing evaluation, in combination with the planned BSA, will meet the necessary requirements for a hospital-based, clinical BNCT system.

Comparison of the Medical Uses and Cellular Effects of High and Low Linear Energy Transfer Radiation.

Exposure to ionizing radiation can occur during medical treatments, from naturally occurring sources in the environment, or as the result of a nuclear accident or thermonuclear war. The severity of cellular damage from ionizing radiation exposure is dependent upon a number of factors including the absorbed radiation dose of the exposure (energy absorbed per unit mass of the exposure), dose rate, area and volume of tissue exposed, type of radiation (e.g., X-rays, high-energy gamma rays, protons, or neutrons) and linear energy transfer. While the dose, the dose rate, and dose distribution in tissue are aspects of a radiation exposure that can be varied experimentally or in medical treatments, the LET and eV are inherent characteristics of the type of radiation. High-LET radiation deposits a higher concentration of energy in a shorter distance when traversing tissue compared with low-LET radiation. The different biological effects of high and low LET with similar energies have been documented in vivo in animal models and in cultured cells. High-LET results in intense macromolecular damage and more cell death. Findings indicate that while both low- and high-LET radiation activate non-homologous end-joining DNA repair activity, efficient repair of high-LET radiation requires the homologous recombination repair pathway. Low- and high-LET radiation activate p53 transcription factor activity in most cells, but high LET activates NF-kB transcription factor at lower radiation doses than low-LET radiation. Here we review the development, uses, and current understanding of the cellular effects of low- and high-LET radiation exposure.

Emodin coupled with high LET neutron beam-a novel approach to treat on glioblastoma.

The primary motivation of this investigative study is trying to find an alternative treatment that can be used to slow down or treat glioblastoma due to the witnessed toxic side effects of the current drugs coupled with limited effectiveness in overall treatment. Consequently, a Chinese plant extract emodin proves to play a critical role in this investigative study since results from the Western blot and the other accompanying assays for anti-cancer effects indicate that it cannot work a lot to suppress cell migration and possible invasion, but rather emodin can be combined with radiation to give desired outcomes. Our result shows that the kind of radiation which acts well with emodin is neutron radiation rather than gamma radiation. Emodin significantly enhanced the radiosensitivity of LN18 and LN428 cells to γ-rays through MTT assay and cell counting. Accordingly, exposure to neutron radiation in the presence of emodin induced apoptotic cell death and autophagic cell death to a significantly higher extent, and suppressed cell migration and invasiveness more robustly. These effects are presumably due to the ability of emodin to amplify the effective dose from neutron radiation more efficiently. Thus, the study below is one such trial towards new interventional discovery and development in relation to glioblastoma treatment.

РОЗВИТОК ПРОФЕСІЙНОГО ІМІДЖУ ФАХІВЦІВ ГОТЕЛЬНО-РЕСТОРАННОЇ СПРАВИ ЧЕРЕЗ ЧИТАННЯ АНГЛОМОВНИХ ПРОФЕСІЙНИХ ТЕКСТІВ

The article deals with future hotel and restaurant professional image development with the help of reading professionally oriented texts in English. It is noted that the general training courses play an important role in the future hotel and restautant specialists’ professional image formation. The course “The Foreign Language of Professional Communications” belongs to the general training courses. Reading is considered as one of the important elements of speech activity. It is a system-forming basis for the information and academic skills formation, and affects the future specialists’ image. The aim of the article is to highlight the influence of the English professional texts on future hotel and restaurant specialists’ professional image development. The scholars’ viewpoints concerning image, professional image, choosing texts and the methodology of working with the texts are considered in the article. The authors believe that working with the English language texts of professional direction plays an important role in shaping the future hotel and restaurant business specialists’ professional image development. The authors’ own experience of teaching at high school let them to elaborate their own strategy of the students’ working with professionally oriented texts. The authors believe that pre-text, text, and post-text activities are used to help the students working with the texts. It is noted that working with texts stimulates students to independent work, develops the ability to search for the necessary information. Expanding the vocabulary becomes important when working with texts, which in turn affects communicative competence, which is a component of professional image. Different online platforms such as Moodle, Vseosvita, Quizlet, Google docs, Google presentations and Canva used to work with texts online are considered. It is noted that working with professional texts will teach the students to work with various types of documents: a job application, a resume, a cover letter, and other types of business and e-mails. The problem of studying the future hotel and restaurant business specialists’ business etiquette of acquires further study.

Proton induced DNA double strand breaks at the Bragg peak: Evidence of enhanced LET effect.

PurposeTo investigate DNA double strand breaks (DSBs) induced by therapeutic proton beams in plateau and Bragg peak to demonstrate DSB induction due to the higher LET in the Bragg peak.Materials and MethodspUC19 plasmid DNA samples were irradiated to doses of 1000 and 3000 Gy on a Mevion S250i proton system with a monoenergetic, 110 MeV, proton beam at depths of 2 and 9.4 cm, corresponding to a position on the plateau and distal Bragg peak of the beam, respectively. The irradiated DNA samples were imaged by atomic force microscopy for visualization of individual DNA molecules, either broken or intact, and quantification of the DNA fragment length distributions for each of the irradiated samples. Percentage of the broken DNA and average number of DSBs per DNA molecule were obtained.ResultsCompared to irradiation effects in the plateau region, DNA irradiated at the Bragg peak sustained more breakage at the same dose, yielding more short DNA fragments and higher numbers of DSB per DNA molecule.ConclusionThe higher LET of proton beams at the Bragg peak results in more densely distributed DNA DSBs, which supports an underlying mechanism for the increased cell killing by protons at the Bragg peak.

A new model for predicting proton SEE cross sections based on heavy ion data

Based on the physical mechanism of the proton single event effects (SEEs), a new analytical model is proposed to predict the proton SEE cross sections of electronic devices from the heavy ion data. The experimental data of five SRAMs from our experiments and the literature are used to test the new model, and the predicted results agree well with them. The existing models only apply to the devices with low LET threshold whose proton SEE cross sections are dominated by the p + Si reactions, and cannot predict the angular effects. Compared to them, our model applies to the devices with from low to high LET threshold whose proton SEE cross sections are dominated by the proton interactions with silicon and/or high-Z materials, and can also predict the angular effects. Moreover, for two SRAMs with low LET threshold, our model performs much better than two classic models, the BGR and microdosimetry models, in predicting their proton SEE cross sections at normal incidence. A new physical concept called the indirect ionization power of protons, which is very helpful for understanding the proton SEE mechanism, is put forward and used in our model. It is expected that the new model will be widely used in studying the proton SEE mechanism, predicting the proton SEE cross sections and on-orbit error rates of electronic devices in space.

Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer.

Simple SummaryBNCT is a biologically targeted, densely ionizing form of radiation therapy that allows for increased tumor cell kill, while reducing toxicity to surrounding normal tissues. Although BNCT has been investigated in the treatment of head and neck cancers and recurrent brain tumors, its applicability to breast cancer has not been previoulsy investigated. In this review we discuss the physical and biological properties of various boronated compounds, and advantages and challenges associated with the potential use of BNCT in the treatment of breast cancer. BNCT is a high LET radiation therapy modality that allows for biologically targeted radiation delivery to tumors while reducing normal tissue impacts. Although the clinical use of BNCT has largely been limited to phase I/II trials and has primarily focused on difficult-to-treat malignancies such as recurrent head and neck cancer and recurrent gliomas, recently there has been a renewed interest in expanding the use of BNCT to other disease sites, including breast cancer. Given its high LET characteristics, its biologically targeted and tumor specific nature, as well as its potential for use in complex treatment settings including reirradiation and widespread metastatic disease, BNCT offers several unique advantages over traditional external beam radiation therapy. The two main boron compounds investigated to date in BNCT clinical trials are BSH and BPA. Of these, BPA in particular shows promise in breast cancer given that is taken up by the LAT-1 amino acid transporter that is highly overexpressed in breast cancer cells. As the efficacy of BNCT is directly dependent on the extent of boron accumulation in tumors, extensive preclinical efforts to develop novel boron delivery agents have been undertaken in recent years. Preclinical studies have shown promise in antibody linked boron compounds targeting ER/HER2 receptors, boron encapsulating liposomes, and nanoparticle-based boron delivery systems. This review aims to summarize the physical and biological basis of BNCT, the preclinical and limited clinical data available to date, and discuss its potential to be utilized for the successful treatment of various breast cancer disease states.

Determination of ion recombination and polarity effects for the PTW Advanced Markus ionization chamber in synchrotron based scanned proton and carbon ion beams

The aim of this work was the investigation of the ion recombination and polarity factors (ksat ad kpol) for a PTW Advanced Markus ionization chamber exposed to proton and carbon ion beams at the Centro Nazionale di Adroterapia Oncologica. Measurements with protons were specifically dedicated for ocular treatments, in the low energy range and for small, collimated scanning fields. For both protons and carbon ions, several measurements were performed by delivering a 2D single energy layer of 3x3 cm2 and homogeneous, biologically-optimized SOBPs. Data were collected at different depths in water, by varying the voltage values of the ionization chamber and for two different dose rates (the nominal one and one reduced to 20% of it). The ksat-values were determined from extrapolation of the saturation curves. Furthermore kpol-values were calculated using the recommendations from the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice.Results showed that the Advanced Markus performs optimally in this clinical scenario characterized by small treatment volumes and high dose gradients although for both particle types, but particularly for carbon ions, a charge multiplication effect up to 1.7% occurs at voltage higher than 150 V.For protons, both the ion recombination and polarity corrections were always smaller than 0.3%, for all the analysed cases and adopted dose rates, so not affecting the dosimetric measurements for clinical routine. For carbon ions the polarity effect can be neglected while ion recombination has to be carefully calculated and cannot be neglected since corrections even higher than 1% can be found, especially at high LET measuring points.

Empirical Relative Biological Effectiveness (RBE) for Mandible Osteoradionecrosis (ORN) in Head and Neck Cancer Patients Treated With Pencil-Beam-Scanning Proton Therapy (PBSPT): A Retrospective, Case-Matched Cohort Study.

PurposeTo retrospectively investigate empirical relative biological effectiveness (RBE) for mandible osteoradionecrosis (ORN) in head and neck (H&N) cancer patients treated with pencil-beam-scanning proton therapy (PBSPT).MethodsWe included 1,266 H&N cancer patients, of which, 931 patients were treated with volumetric-modulated arc therapy (VMAT) and 335 were treated with PBSPT. Among them, 26 VMAT and 9 PBSPT patients experienced mandible ORN (ORN group), while all others were included in the control group. To minimize the impact of the possible imbalance in clinical factors between VMAT and PBSPT patients in the dosimetric comparison between these two modalities and the resulting RBE quantification, we formed a 1:1 case-matched patient cohort (335 VMAT patients and 335 PBSPT patients including both the ORN and control groups) using the greedy nearest neighbor matching of propensity scores. Mandible dosimetric metrics were extracted from the case-matched patient cohort and statistically tested to evaluate the association with mandibular ORN to derive dose volume constraints (DVCs) for VMAT and PBSPT, respectively. We sought the equivalent constraint doses for VMAT so that the critical volumes of VMAT were equal to those of PBSPT at different physical doses. Empirical RBEs of PBSPT for ORN were obtained by calculating the ratio between the derived equivalent constraint doses and physical doses of PBSPT. Bootstrapping was further used to get the confidence intervals.ResultsClinical variables of age, gender, tumor stage, prescription dose, chemotherapy, hypertension or diabetes, dental extraction, smoking history, or current smoker were not statistically related to the incidence of ORN in the overall patient cohort. Smoking history was found to be significantly associated with the ORN incidence in PBSPT patients only. V40Gy[RBE], V50Gy[RBE], and V60Gy[RBE] were statistically different (p<0.05) between the ORN and control group for VMAT and PBSPT. Empirical RBEs of 1.58(95%CI: 1.34-1.64), 1.34(95%CI: 1.23-1.40), and 1.24(95%: 1.15-1.26) were obtained for proton dose at 40 Gy[RBE=1.1], 50 Gy[RBE=1.1] and 60 Gy[RBE=1.1], respectively.ConclusionsOur study suggested that RBEs were larger than 1.1 at moderate doses (between 40 and 60 Gy[RBE=1.1]) with high LET for mandible ORN. RBEs are underestimated in current clinical practice in PBSPT. The derived DVCs can be used for PBSPT plan evaluation and optimization to minimize the incidence rate of mandible ORN.

Effects of Ionizing Radiation and Long-Term Storage on Hydrated vs. Dried Cell Samples of Extremophilic Microorganisms.

A main factor hampering life in space is represented by high atomic number nuclei and energy (HZE) ions that constitute about 1% of the galactic cosmic rays. In the frame of the “STARLIFE” project, we accessed the Heavy Ion Medical Accelerator (HIMAC) facility of the National Institute of Radiological Sciences (NIRS) in Chiba, Japan. By means of this facility, the extremophilic species Haloterrigena hispanica and Parageobacillus thermantarcticus were irradiated with high LET ions (i.e., Fe, Ar, and He ions) at doses corresponding to long permanence in the space environment. The survivability of HZE-treated cells depended upon either the storage time and the hydration state during irradiation; indeed, dry samples were shown to be more resistant than hydrated ones. With particular regard to spores of the species P. thermantarcticus, they were the most resistant to irradiation in a water medium: an analysis of the changes in their biochemical fingerprinting during irradiation showed that, below the survivability threshold, the spores undergo to a germination-like process, while for higher doses, inactivation takes place as a consequence of the concomitant release of the core’s content and a loss of integrity of the main cellular components. Overall, the results reported here suggest that the selected extremophilic microorganisms could serve as biological model for space simulation and/or real space condition exposure, since they showed good resistance to ionizing radiation exposure and were able to resume cellular growth after long-term storage.

Effects of radical scavengers on nanocomposite Fricke gel for heavy ion beam irradiation

NC-FG (nanocomposite Fricke gel) dosimeter is a 3D dosimeter for heavy ion beam without LET dependence. In this study, we evaluate the effects of silver perchlorate, a radical scavenger, on NC-FG. We find that radiological properties of NC-FG are changed by small amounts of silver perchlorate. Especially, dose response at high LET enhanced.

Per-voxel constraints to minimize hot spots in linear energy transfer-guided robust optimization for base of skull head and neck cancer patients in IMPT.

Due to the employment of quadratic programming using soft constraints to implement dose volume constraints and the "trial-and-error" procedure needed to achieve a clinically acceptable plan, conventional dose volume constraints (upper limit) are not adequately effective in controlling small and isolated hot spots in the dose/linear energy transfer (LET) distribution. Such hot spots can lead to adverse events. In order to mitigate the risk of brain necrosis, one of the most clinically significant adverse events in patients receiving intensity-modulated proton therapy (IMPT) for base of skull (BOS) cancer, we propose per-voxel constraints to minimize hot spots in LET-guided robust optimization. Ten BOS cancer patients treated with IMPT were carefully selected by meeting one of the following conditions: (1) diagnosis of brain necrosis during follow-up; and (2) considered high risk for brain necrosis by not meeting dose constraints to the brain. An optimizing structure (BrainOPT) and an evaluating structure (BrainROI) that both contained the aforementioned hot dose regions in the brain were generated for optimization and evaluation, respectively. Two plans were generated for every patient: one using conventional dose-only robust optimization, the other using LET-guided robust optimization. The impact of LET was integrated into the optimization via a term of extra biological dose (xBD). A novel optimization tool of per-voxel constraints to control small and isolated hot spots in either the dose, LET, or combined (dose/LET) distribution was developed and used to minimize dose/LET hot spots of the selected structures. Indices from dose-volume histogram (DVH) and xBD dose-volume histogram (xBDVH) were used in the plan evaluation. A newly developed tool of the dose-LET-volume histogram (DLVH) was also adopted to illustrate the underlying mechanism. Wilcoxon signed-rank test was used for statistical comparison of the DVH and xBDVH indices between the conventional dose-only and the LET-guided robustly optimized plans. Per-voxel constraints effectively and efficiently minimized dose hot spots in both dose-only and LET-guided robust optimization and LET hot spots in LET-guided robust optimization. Compared to the conventional dose-only robust optimization, the LET-guided robust optimization could generate plans with statistically lower xBD hot spots in BrainROI (VxBD,50Gy[RBE], p=0.009; VxBD,60Gy[RBE], p=0.025; xBD1cc, p=0.017; xBD2cc, p=0.022) with comparable dose coverage, dose hot spots in the target, and dose hot spots in BrainROI. DLVH analysis indicated that LET-guided robust optimization could either reduce LET at the same dose level or redistribute high LET from high dose regions to low dose regions. Per-voxel constraint is a powerful tool to minimize dose/LET hot spots in IMPT. The LET-guided robustly optimized plans outperformed the conventional dose-only robustly optimized plans in terms of xBD hot spots control.

DNA repair inhibitors sensitize cells differently to high and low LET radiation

The aim of this study was to investigate effects of high LET α-radiation in combination with inhibitors of DDR (DNA-PK and ATM) and to compare the effect with the radiosensitizing effect of low LET X-ray radiation. The various cell lines were irradiated with α-radiation and with X-ray. Clonogenic survival, the formation of micronuclei and cell cycle distribution were studied after combining of radiation with DDR inhibitors. The inhibitors sensitized different cancer cell lines to radiation. DNA-PKi affected survival rates in combination with α-radiation in selected cell lines. The sensitization enhancement ratios were in the range of 1.6–1.85 in cancer cells. ATMi sensitized H460 cells and significantly increased the micronucleus frequency for both radiation qualities. ATMi in combination with α-radiation reduced survival of HEK293. A significantly elicited cell cycle arrest in G2/M phase after co-treatment of ATMi with α-radiation and X-ray. The most prominent treatment effect was observed in the HEK293 by combining α-radiation and inhibitions. ATMi preferentially sensitized cancer cells and normal HEK293 cells to α-radiation. DNA-PKi and ATMi can sensitize cancer cells to X-ray, but the effectiveness was dependent on cancer cells itself. α-radiation reduced proliferation in primary fibroblast without G2/M arrest.

Strategy to mitigate single event upset in 14-nm CMOS bulk FinFET technology

Three-dimensional (3D) TCAD simulations demonstrate that reducing the distance between the well boundary and N-channel metal–oxide semiconductor (NMOS) transistor or P-channel metal–oxide semiconductor (PMOS) transistor can mitigate the cross section of single event upset (SEU) in 14-nm complementary metal–oxide semiconductor (CMOS) bulk FinFET technology. The competition of charge collection between well boundary and sensitive nodes, the enhanced restoring currents and the change of bipolar effect are responsible for the decrease of SEU cross section. Unlike dual-interlock cell (DICE) design, this approach is more effective under heavy ion irradiation of higher LET, in the presence of enough taps to ensure the rapid recovery of well potential. Besides, the feasibility of this method and its effectiveness with feature size scaling down are discussed.