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At least 19 records

CBP/P300 Inhibitors Mitigate Radiation-Induced GI Syndrome by Promoting Intestinal Stem Cell-Mediated Crypt Regeneration

Radiation-induced gastrointestinal syndrome (RIGS) is currently the main cause of death for people exposed to a high dose of irradiation during nuclear incidents, and there is currently no approved effective therapy. Here, we found that CBP/P300 inhibitors, with high efficacy and low toxicity, might be promising radiation mitigators that can cure RIGS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature

As more cancer patients survive their disease, concerns about radiation therapy–induced side effects have increased. The concept of radioprotection and radiation injury mitigation and treatment offers the possibility to enhance the therapeutic ratio of radiation therapy by limiting radiation therapy–induced normal tissue injury without compromising its antitumor effect. Advances in the understanding of the underlying mechanisms of radiation toxicity have stimulated radiation oncologists to target these pathways across different organ systems. These generalized radiation injury mechanisms include production of free radicals such as superoxides, activation of inflammatory pathways, and vascular endothelial dysfunction leading to tissue hypoxia. There is a significant body of literature evaluating the effectiveness of various treatments in preventing, mitigating, or treating radiation-induced normal tissue injury. Whereas some reviews have focused on a specific disease site or agent, this critical review focuses on a mechanistic classification of activity and assesses multiple agents across different disease sites. The classification of agents used herein further offers a useful framework to organize the multitude of treatments that have been studied. Many commonly available treatments have demonstrated benefit in prevention, mitigation, and/or treatment of radiation toxicity and warrant further investigation. These drug-based approaches to radioprotection and radiation injury mitigation and treatment represent an important method of making radiation therapy safer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Targeting the Renin–Angiotensin System Combined With an Antioxidant Is Highly Effective in Mitigating Radiation-Induced Lung Damage

Purpose: To investigate the outcome of suppression of the renin angiotensin system using captopril combined with an antioxidant (Eukarion [EUK]-207) for mitigation of radiation-induced lung damage in rats. Methods and Materials: The thoracic cavity of female Sprague-Dawley rats was irradiated with a single dose of 11 Gy. Treatment with captopril at a dose of 40 mg/kg/d in drinking water and EUK-207 given by subcutaneous injection (8 mg/kg daily) was started 1 week after irradiation (PI) and continuing until 14 weeks PI. Breathing rate was monitored until the rats were killed at 32 weeks PI, when lung fibrosis was assessed by lung hydroxyproline content. Lung levels of the cytokine transforming growth factor-β1 and macrophage activation were analyzed by immunohistochemistry. Oxidative DNA damage was assessed by 8-hydroxy-2-deoxyguanosine levels, and lipid peroxidation was measured by a T-BARS assay. Results: The increase in breathing rate in the irradiated rats was significantly reduced by the drug treatments. The drug treatment also significantly decreased the hydroxyproline content, 8-hydroxy-2-deoxyguanosine and malondialdehyde levels, and levels of activated macrophages and the cytokine transforming growth factor-β1 at 32 weeks. Almost complete mitigation of these radiation effects was observed by combining captopril and EUK-207. Conclusion: Captopril and EUK-207 can provide mitigation of radiation-induced lung damage out to at least 32 weeks PI after treatment given 1-14 weeks PI. Overall the combination of captopril and EUK-207 was more effective than the individual drugs used alone.

60 APPLIED LIFE SCIENCES↗

Radiation Damage Mitigation in FeCrAl Alloy at Sub-Recrystallization Temperatures

Traditional defect recovery methods rely on high-temperature annealing, often exceeding 750 °C for FeCrAl. In this study, we introduce electron wind force (EWF)-assisted annealing as an alternative approach to mitigate irradiation-induced defects at significantly lower temperatures. FeCrAl samples irradiated with 5 MeV Zr 2+ ions at a dose of 10 14 cm −2 were annealed using EWF at 250 °C for 60 s. We demonstrate a remarkable transformation in the irradiated microstructure, where significant increases in kernel average misorientation (KAM) and low-angle grain boundaries (LAGBs) typically indicate heightened defect density; the use of EWF annealing reversed these effects. X-ray diffraction (XRD) confirmed these findings, showing substantial reductions in full width at half maximum (FWHM) values and a realignment of peak positions toward their original states, indicative of stress and defect recovery. To compare the effectiveness of EWF, we also conducted traditional thermal annealing at 250 °C for 7 h, which proved less effective in defect recovery as evidenced by less pronounced improvements in XRD FWHM values.

FeCrAl alloys↗

Weakening aerosol direct radiative effects mitigate climate penalty on Chinese air quality

Future climate change may worsen air quality in many regions. However, evaluations of this ‘climate penalty’ on air quality have typically not assessed the radiative effects of changes in short-lived aerosols. Additionally, China’s clean air goals will decrease pollutant emissions and aerosol loadings, with concomitant weakening of aerosol feedbacks. In this work, we assess how such weakened aerosol direct effects alter the estimates of air pollution and premature mortality in China attributable to mid-century climate change under Representative Concentration Pathway 4.5. We found that weakening aerosol direct effects cause boundary layer changes that facilitate diffusion. This reduces air-pollution exposure (~4% in fine particulate matter) and deaths (13,800 people per year), which largely offset the additional deaths caused by greenhouse gas-dominated warming. These results highlight the benefits of reduced pollutant emissions through weakening aerosol direct effects and underline the potential of pollution control measures to mitigate climate penalties locked in by greenhouse gas emissions.

54 ENVIRONMENTAL SCIENCES↗

Double side read-out technique for mitigation of radiation damage effects in PbWO 4 crystals

Test beam results of a calorimetric module based on 3×3×22 cm 3 PbWO 4 crystals, identical to those used in the CMS ECAL Endcaps, read out by a pair of photodetectors coupled to the two opposite sides (front and rear) of each crystal are presented. Nine crystals with different level of induced absorption, from 0 to 20 m -1 , have been tested using electrons in the 50–200 GeV energy range. Photomultiplier tubes have been chosen as photodetectors to allow for a precise measurement of highly damaged crystals. The information provided by this double side read-out configuration allows to correct for event-by-event fluctuations of the longitudinal development of electromagnetic showers. By strongly mitigating the effect of non-uniform light collection efficiency induced by radiation damage, the double side read-out technique significantly improves the energy resolution with respect to a single side read-out configuration. The non-linearity of the response arising in damaged crystals is also corrected by a double side read-out configuration and the response linearity of irradiated crystals is restored. In high radiation environments at future colliders, as it will be the case for detectors operating during the High Luminosity phase of the Large Hadron Collider, defects can be created inside the scintillator volume leading to a non-uniform response of the calorimetric cell. As a result, the double side read-out technique presented in this study provides a valuable way to improve the performance of calorimeters based on scintillators whose active volumes are characterized by high aspect ratio cells similar to those used in this study.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation-Induced Pulmonary Fibrosis in a Murine Model

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. Methods and Materials: C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for β-galactosidase activity. Results: Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 ± 11.8 μg per lung; irradiation plus rapamycin, 21.4 ± 6.0 μg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1β and transforming growth factor β induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). Conclusions: Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Overview of Nuclear Integration Activities for Mitigation of Radiation Loads to ITER Superconducting Magnets

The Nuclear Integration Unit (NIU) is a trans-departmental team from the ITER Organization and Domestic Agencies, responsible for all nuclear integration aspects of the facility and for ensuring that systems and components are suitable for their radiation environment and satisfy all related performance requirements. This is a very challenging task namely due to the large number of systems, their still evolving designs, the intricate and far-reaching impacts of these in nuclear responses everywhere, and the complex world-wide distribution of procurement responsibilities. A sound systems engineering approach that involves all relevant experts and stakeholders, and trades-off between different performance requirements in an optimum way, needs to be taken and sustained during design evolution and construction, always with the objective of final overall project success. One of the most important current occupations of the NIU is the evaluation of, and protection from, radiation conditions to superconducting magnets during plasma operations, and particularly nuclear heating. This requires neutronic analyses in massive computer resources, with state-of-the-art methods and complex, extensive computer models. The main ITER superconducting magnet systems subject to significant nuclear loads are the toroidal field coils (TFCs) and the poloidal field coils (PFCs). These are illustrated in Fig. 1. Nuclear responses in these depend mostly on the design of all in-vessel (blankets, manifolds, divertor, in-vessel coils, port plugs), vessel and thermal shield components. Sources to consider are the 500 MW DT burning plasma (14.1 MeV neutrons) and the activated water in the in-vessel cooling system (photons up to 7 MeV from N-16 and neutrons up to 3.5 MeV from N-17). This paper discusses a snapshot of the present understanding of nuclear heat conditions in both the TFC and PFC magnets. This includes integral values and distributions, as well as best estimates from computations and conservative upper estimates by consideration of systematic effects and random uncertainties. The computer models, methods and assumptions used for evaluation of these responses are described. Nuclear integration aspects and ongoing efforts to study and implement additional shielding and other mitigating measures are also discussed.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Nature-based climate solutions can help mitigate the radiative forcing that follows deforestation

Widespread expansion of agriculture and forestry has altered the surface of the Earth, the composition of the atmosphere, and as a result, the climate. Here we quantify the radiative forcing caused by the historical deforestation of an ecoregion in the U.S. Upper Midwest and the adoption of eight nature-based climate solutions. We combined regional forest inventory data with over three decades of remote sensing and in situ data from a replicated land use change experiment. Deforestation of the region caused net global warming (1626 ± 44 µW m -2 ), mainly from the 76 % reduction of ecosystem carbon stocks, but also from the 84 % reduction of the soil methane sink and the 115 % increase in soil nitrous oxide emissions. The associated albedo increase offset 24 % of this greenhouse gas induced warming. For the adoption of nature-based climate solutions, we found that conservation agriculture can provide -39 to -76 ± 31 µW m -2 of climate mitigation over a 100-year time period while short/medium length forestry rotations can provide more at -296 to -881 ± 44 µW m -2 and natural forest regeneration can provide the most at -1555 ± 44 µW m -2 . As the impacts of climate change on nature and society intensify, consideration should be given to the climate mitigation, habitat, and ecosystem services that nature-based climate solutions can provide.

54 ENVIRONMENTAL SCIENCES↗

Virtual Bronchoscopy-Guided Treatment Planning to Map and Mitigate Radiation-Induced Airway Injury in Lung SAbR

Radiation injury to the bronchial tree is an important yet poorly understood potential side effect in lung stereotactic ablative radiation therapy (SAbR). We investigate the integration of virtual bronchoscopy in radiation therapy planning to quantify dosage to individual airways. We develop a risk model of airway collapse and develop treatment plans that reduce the risk of radiation-induced airway injury.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Radiation damage in nanostructured materials

Materials subjected to high dose irradiation by energetic particles often experience severe damage in the form of drastic increase of defect density, and significant degradation of their mechanical and physical properties. Extensive studies on radiation effects in materials in the past few decades show that, although nearly no materials are immune to radiation damage, the approaches of deliberate introduction of certain types of defects in materials before radiation are effective in mitigating radiation damage. Nanostructured materials with abundant internal defects have been extensively investigated for various applications. The field of radiation damage in nanostructured materials is an exciting and rapidly evolving arena, enriched with challenges and opportunities. In this review article, we summarize and analyze the current understandings on the influence of various types of internal defect sinks on reduction of radiation damage in primarily nanostructured metallic materials, and partially on nanoceramic materials. We also point out open questions and future directions that may significantly improve our fundamental understandings on radiation damage in nanomaterials. Finally, the integration of extensive research effort, resources and expertise in various fields may eventually lead to the design of advanced nanomaterials with unprecedented radiation tolerance.

36 MATERIALS SCIENCE↗

Radiation Enhanced Absorption of Frank Loops by Nanovoids in Cu

Neutron and heavy ion irradiation generally induces voids in metallic materials, and continuous radiations typically result in void swelling and mechanical failure of the irradiated materials. Recent experiments showed that nanovoids in nanotwinned copper could act as sinks for radiation-induced Frank loops, significantly mitigating radiation damage [Y. Chen et al., Nat. Commun. 6:7036 (2015)]. In this paper, we report on structural evolution of Frank loops under cascades and address the role of nanovoids in absorbing Frank loops in detail by using molecular dynamics simulations. Results show that a stand-alone Frank loop is stable under cascades. When Frank loops are adjacent to nanovoids, the diffusion of a group of atoms from the loop into nanovoids is accomplished via the formation and propagation of dislocation loops. The loop-nanovoid interactions result in the shrinkage of the nanovoids and the Frank loops.

36 MATERIALS SCIENCE↗

Single Event Transient Response of Vertical and Lateral Waveguide-Integrated Germanium Photodiodes

Pulsed-laser induced single event current measurements on two geometries of waveguide-integrated germanium photodiodes were conducted over a range of operating voltages to examine the impact of photodiode geometry on the transient response. Vertical PIN photodiodes exhibit transients with a duration that is relatively independent of the operating voltage while the transient duration in lateral PIN photodiodes depends on operating voltage. Furthermore, the experimental measurements facilitate identification of device dimensions that impact the transient response. In this work, these results can be used to identify potential radiation mitigation strategies for photodiodes operating in a radiation environment. Understanding the implications of design choices is critical for designing integrated photonic systems that balance system performance with tolerance for radiation degradation.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Conformational variation of proteins at room temperature is not dominated by radiation damage

Protein crystallography data collection at synchrotrons is routinely carried out at cryogenic temperatures to mitigate radiation damage. Although damage still takes place at 100 K and below, the immobilization of free radicals increases the lifetime of the crystals by approximately 100-fold. Recent studies have shown that flash-cooling decreases the heterogeneity of the conformational ensemble and can hide important functional mechanisms from observation. These discoveries have motivated increasing numbers of experiments to be carried out at room temperature. However, the trade-offs between increased risk of radiation damage and increased observation of alternative conformations at room temperature relative to cryogenic temperature have not been examined. A considerable amount of effort has previously been spent studying radiation damage at cryo-temperatures, but the relevance of these studies to room temperature diffraction is not well understood. Here, the effects of radiation damage on the conformational landscapes of three different proteins ( T. danielli thaumatin, hen egg-white lysozyme and human cyclophilin A) at room (278 K) and cryogenic (100 K) temperatures are investigated. Increasingly damaged datasets were collected at each temperature, up to a maximum dose of the order of 10 7 Gy at 100 K and 10 5 Gy at 278 K. Although it was not possible to discern a clear trend between damage and multiple conformations at either temperature, it was observed that disorder, monitored by B -factor-dependent crystallographic order parameters, increased with higher absorbed dose for the three proteins at 100 K. At 278 K, however, the total increase in this disorder was only statistically significant for thaumatin. A correlation between specific radiation damage affecting side chains and the amount of disorder was not observed. Lastly, this analysis suggests that elevated conformational heterogeneity in crystal structures at room temperature is observed despite radiation damage, and not as a result thereof.

59 BASIC BIOLOGICAL SCIENCES↗