Alzheimer’s disease (AD) is one of the primary causes of disability and dependency among aging populations worldwide. Neuroinflammation may be a potential therapeutic target in AD. Moreover, ionizing radiation may be a tool for modulating neuroinflammation. Here, we used three mouse lines—C57Bl/6 and the transgenic AD models 5xFAD and Tau P301S—to investigate the effects of combined ionizing radiation (γ-rays and carbon-12 nuclei) on emotional state, cognitive abilities, and markers of microglial activation. The obtained data show that combined irradiation results in enhanced exploratory behavior and spatial learning in the C57Bl/6 mice. The same changes, as well as a decrease in anxiety, were found in the Tau P301S mice. Irradiation of the 5xFAD mice resulted in improved welfare and ability to discriminate odors. At the same time, irradiation led to an increase in the level of pro- and anti-inflammatory cytokines in the prefrontal cortex and, to a lesser extent, in the hippocampus of the C57Bl/6 and Tau P301S mice. An increase in macrophage inflammatory protein-1α in the prefrontal cortex and a decrease in interleukin 2β in the hippocampus were found in the 5xFAD mice. Taken together, our data indicate that ionizing radiation exposure is an adequate tool to modulate microglial activity in the brain and may provide cognitive and non-cognitive behavioral benefits in neurodegenerative disease conditions.

Exposure to ionizing radiation during manned deep space missions to Mars could lead to functional impairments of the central nervous system, which may compromise the success of the mission and affect the quality of life for returning astronauts. Along with radiation-induced changes in cognitive abilities and emotional status, the effects of increased motor activity were observed. The mechanisms behind these phenomena still remain unresolved. We conducted a study on grip strength, locomotor activity and intrasession habituation to novelty in 5-month-old rats after exposure to radiation (combined 0.4 Gy gamma-rays and 0.14 Gy 12C nuclei). At the same time, we carried out neurochemical and molecular analysis of the nucleus accumbens (NAc) and the dorsal striatum (dST). The study revealed radiation-induced hyperlocomotion and enhanced habituation. It also showed an increase in choline concentration and a decreased in 5-hydroxyindoleacetic acid concentration in the NAc after irradiation. In addition to this, a down-regulation of syntaxin 1A in NAc and dST as well as up-regulation α-synuclein in NAc were observed. The obtained data indicate both the damaging effect of irradiation on striatum tissues and the initiation of neuronal/axonal regeneration processes. It is hypothesized that the increase in choline concentration in NAc and the decreased content of syntaxin 1A in dST may be the part of the mechanism responsible for the radiation-induced hyperlocomotion.

A study of molecular mechanisms of the neurobiological effects of the combined exposure to 10‑day antiorthostatic suspension (AnOS), daily γ-irradiation, and irradiation with carbon ions in rats was carried out. Analysis of molecular changes in dopamine receptors of the hippocampus revealed changes in irradiated rats; in particular, increased expression of monoamine oxidase A, the substrates of which are serotonin, adrenaline, norepinephrine and histamine, was found. The spectral and amplitude–frequency EEG characteristics of rats after the specified influences were studied. Comparison of primary EEG results revealed a tendency towards a decrease in the frequencies of the first peak in irradiated rats regardless of rhythms. In irradiated animals, a tendency towards a decrease in the center frequencies and amplitudes of the most pronounced peak of the EEG spectrum and a decrease in the center frequency and amplitude within the delta rhythm of the maximum peak of the spectrum was observed. Increased anxiety and somewhat accelerated learning in the Morris tests and conditioned reflexes of active avoidance in the shuttle chamber were observed in the behavior of rats, which was consistent with changes in some metabolites of dopamine and serotonin in the hippocampus.

Neutron monitors with the gas filled proportional counters inside and first data were presented at RuPAC-2018 and RuPAC-2021 conferences. It is planned to use such devices to monitor the stability of irradiation conditions during ra- diation therapy sessions. We present here the calibration procedure for these monitors at AmBe neutron source, and the new data. These monitors have been used to measure the neutron fluence behind the shielding of the 450 MeV/nucleon carbon beam based experimental facility “Shared use Center – radiobiological stand with the carbon beam of the U-70 accelerator at IHEP”. The measurements were supported by the set of extensive simulations using the CERN FLUKA code. Good agreement between the FLUKA simulations and measurements was shown. Even single monitor with lead insertion calibrated at AmBe neutron source allows to have a good result in the real neutron field. The possibility to estimate the fluence of the high energy neutrons with the energy above 10 MeV using data from the pair of monitors was demonstrated. To improve the quality of the measurements one needs to take into account difference between calibration and measurements conditions.

More than 9 billion tons of industrial and consumption wastes are generated annually, of which about 90% are from mining of minerals, including the share of over 70% from coal mining and about 25% from metal ore mining. Tackling the issues related to mining waste management is a highly topical task that involves a number of aspects in the fields of legislation, scientific, methodological and design support, as well as technical and technological solutions. In order to reduce the negative consequences associated with the disposal of such a significant amount of waste, a governmental concept of rational nature management has been formulated, which aims to regulate its use and economic rehabilitation. Legislative initiatives stimulate environmentally conscious mining and comprehensive use of georesources. This calls for the development of a scientific basis for designing mining engineering systems and the search for new environmentally balanced technical and technological solutions for deposit development. Examples of large-scale and successful use of ecologically balanced solutions are the development projects of the Mikheyevskoye and Tarutinskoye deposits, where, in the case of the sinking mining system, the overburden is planned to be used for filling the mined-out space, and the dumps are placed both taking into account the maximum preservation of the forest area and to ensure natural ventilation of the open pits. At Mikheyevsky GOK, a solution is being implemented to combine the construction of a dump site and a tailings dam. The projects for abandonment of the Alexandrinsky mine and the Korkinsky coal mine include the use of mill tailing as the basis for the backfill material preparation. Such solutions ensure both elimination of accumulated damage and reduction of current waste generation.

Currently, the experience in designing installations using extracted carbon ion beams in Russia (the world) is very limited. The medical cabin for ion therapy of channel 26A of the LUCH U-70 project provides a unique opportunity for assessing the effectiveness of biological protection and verifying calculations. The paper presents data from experimental measurements of neutron radiation behind the biological protection of a medical cabin. The data were obtained for two energies of the extracted beam of accelerated carbon nuclei - 400 and 450 MeV/nucleon. The result is compared with the calculation performed using the FLUKA program for a given protection configuration. Good agreement between experimental data and calculations is shown.

The RBS experimental set-up has been working in every accelerator session of the U-70 accelerator complex since 2015. The main users of the set-up are radiobiologists and physicians. The direction of research is radiobiological experiments with extracted beams of accelerated carbon ions and preclinical studies aimed at the development of domestic methods of ion therapy. The requirements for irradiation of samples with carbon ions are very high: irradiation uniformity is no worse than 95%, positioning accuracy is no worse than 0.1 mm, dose delivery accuracy is no worse than ±2.5%. The article describes the instruments and devices that are used to support radiobiological experiments at the RBS installation: a plane-parallel ionization chamber, a mosaic ionization chamber, a water phantom with a 3D movement system, a 6-axis table, a degrader, a laser positioning system, clinical dosimeters. Programs for working with this equipment and archiving the data obtained are described.

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.

We studied neurobiological effects of physical factors modelinginterplanetary spaceflight conditions-microgravity (modeled by antiorthostaticsuspension) and deep space radiation (modeled by quasi-chronic gammairradiation and head irradiation by (12)Cions)-in Long-Evans male rats, taking into account typological characteristicsof their higher nervous activity (HNA). We investigated behavioralchanges, as well as the dynamics of EEG and neurochemical processes inthe brain regions responsible for cognition and emotions (frontalcortex, thalamus, hypothalamus). We found differences in the effectsof the above factors on orientation-exploratory activity and cognitivefunctions in control vs. exposed rats, as well as in animals ofdifferent HNA typologies ("excitable" vs. "inhibited"). These differenceswere underlain by the shift in the balance of the main inhibitoryand excitatory neurotransmitters, GABA and glutamate, as well asin the dopaminergic system. Specifically, rats with the predominanceof excitation learnt faster but were inferior to rats with the predominanceof inhibition in retaining new skills. We also found some changesin the ratio of main EEG rhythms, elicited by experimental exposures.

The combined effect of protective agents (helium-neon laser, ibuprofen, mexidol) and 3 Gy of accelerated carbon ions (12C) on the cognitive abilities of mice was studied. It was shown that the irradiated animals did not exhibit an altered behavior pattern: the level of anxiety was not increased, there was a slower positive dynamics of learning compared to the control, and there was no deficit in the hippocampus-dependent memory. Analysis of variance of learning curves revealed different coefficients of skill acquisition within the experimental groups, with the lowest characteristic for the group irradiated with a dose of 3 Gy 12C without protective agents. In addition, the analysis of the preference for novelty when testing for recognition of a new object showed that this group of animals has a violation of the nonspatial hippocampus-mediated short-term memory.

We studied the effects of single and combined action of protons and carbon ions 12 C 6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e . a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control ( p <0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.

Space radiation, presented primarily by high-charge and -energy particles (HZEs), has a substantial impact on the central nervous system (CNS) of astronauts. This impact, surprisingly, has not only negative but also positive effects on CNS functions. Despite the fact that the mechanisms of this effect have not yet been elucidated, several studies indicate a key role for monoaminergic networks underlying these effects. Here, we investigated the effects of acute irradiation with 450 MeV/n carbon (12C) nuclei at a dose of 0.14 Gy on Wistar rats; a state of anxiety was accessed using a light–dark box, spatial memory in a Morris water maze, and the dynamics of monoamine metabolism in several brain morphological structures using HPLC. No behavioral changes were observed. Irradiation led to the immediate suppression of dopamine turnover in the prefrontal cortex, hypothalamus, and striatum, while a decrease in the level of norepinephrine was detected in the amygdala. However, these effects were transient. The deferred effect of dopamine turnover increase was found in the hippocampus. These data underscore the ability of even low-dose 12C irradiation to affect monoaminergic networks. However, this impact is transient and is not accompanied by behavioral alterations.

Предложена процедура формализации цифрового подхода к трансформации технологических систем

We study the impact of radiation LET on manifestation of HRS/IRR response in Chinese hamster cells ovary cells exposed to radiations used in radiotherapy. Earlier we have investigated this response to carbon ions (455 MeV/amu) in the pristine Bragg curve plateau and behind the Bragg peak, 60Co γ-rays, and 14.5 MeV neutrons. Now we present results of cytogenetic metaphase analysis in plateau-phase CHO-K1 cells irradiated with scanning beam protons (83 MeV) at doses < 1 Gy and additional data for 14.5 MeV neutrons. Dose curves for frequency of total chromosome aberrations (CA, protons), paired fragments (protons, neutrons), aberrant cells (neutrons) had typical HRS/IRR structure: HRS region (up to 0.1 and 0.15 Gy), IRR region (0.1–0.6 Gy and 0.15–0.35 Gy) for protons and neutrons, respectively, and regular dose dependence. Taken together with previous results, the data show that LET increase shifts the HRS upper border (from 0.08–0.1 Gy for γ-rays, protons and plateau carbons to 0.12–0.15 Gy for “tail” carbons and neutrons). The IRR regions shortens (0.52–0.4 γ-rays and protons, 0.25 plateau carbons, 0.2 Gy “tail” carbons and neutrons). CA level of IRR increases by 1.5–2.5 times for carbons as compared to γ-rays and protons. Outside HRS/IRR the yield of CA also enhanced with LET increase. The results obtained for different LET radiations suggest that CHO-K1 cells with G1-like CA manifested the general feature of the HRS/IRR phenomena.

The relative biological efficiency of particle irradiation could be predicted with a wide variety of radiobiological models for various end-points. We validate the forecast of modified Microdosimetric Kinetic Modelin vitrousing combined data of reference Co-60 radiation and carbon ion plateau data for specific cell line to optimize the survival function in spread-out Bragg Peak obtained with an especially designed ridge filter. We used Geant4 Monte-Carlo software to simulate the fragment contribution along Bragg curve inside water phantom, open-source toolkit Survival to predict the expected linear-quadratic model parameters for each fragment, and in-house software to form the total survival curve in spread-out Bragg Peak. The irradiation was performed at U-70 synchrotron with an especially designed Aluminum ridge filter under the control of PTW and in-house ionization chambers. The cell clonogenic assay was conducted with the B14-150 cell line. The data analysis was accomplished using scipy and CERN ROOT. The clonogenic assay represents the survival in spread-out Bragg Peak at different points and qualitatively follows the modeled survival curve very well. The quantitative difference is within 3σ, and the deviation might be explained by the uncertainties of physical modeling using Monte-Carlo methods. Overall, the obtained results are promising for further usage in radiobiological studies or carbon ion radiotherapy. Shaping the survival curve in the region of interest (i.e., spread-out Bragg Peak) is a comprehensive task that requires high-performance computing approaches. Nevertheless, the method's potential application is related to the development of next-generation treatment planning systems for ion beams. This can open a wide range of improvements in patient treatment outcome, provide new optimized fractionation regimes or optimized dose delivery schemes, and serve as an entrance point to the translational science approach.

Modern market conditions are characterized with volatility of the prices and demand for raw materials. Therefore the development of many major mineral deposits in the Russian Federation requires elaboration of the company's development strategy which involves solving complex design tasks to ensure production efficiency in complex geological and mining conditions with proper account of natural and environmental constraints as well as the company's sustainability and viability goals over a long period of time. The article presents one of the approaches that can be used when selecting the development strategy of a mining company with account of environmental constraints. Using a limestone deposit, which name has been changed due to the confidentiality conditions, as an example, the article describes options for technological solutions related to dewatering of its reserves. Implementation of these solutions is aimed at developing and extending the lifetime of the mining operation, mitigating environmental risks and implementing environmental protection measures. Systematization of methods to protect the open pit from ground waters is made based on the complicating factors. An aggregated technical and economic assessment of the presented options of strategic decisions is given.

100 АВГУСТ, 2022, "УГОЛЬ" ГЕОТЕХНОЛОГИЯ Возрастание изменчивости внешней среды функционирования горнодобывающих предприятий и усложнение условий эксплуатации месторождений твердых полезных ископаемых предопределяют изменение подходов и требований к проектно-изыскательским работам.Возникает противоречие: с одной стороны, необходимы выполнение серьезных предпроектных исследований, проработка стратегии развития предприятия, поиск инновационных решений, обеспечивающих эффективное освоение месторождения, с другой стороны, месторождение должно быть вовлечено в отработку в максимально короткие сроки с целью минимизации срока окупаемости и обеспечения инвестиционной привлекательности.Снятие противоречия обеспечивается балансом между концептуальным проектированием и глубиной проработки проектных решений для поиска вариантов и их оптимизации на разных этапах проектирования в рамках единой концепции с учетом условий и требований будущего.Для снижения рисков на первом этапе проектирования рассматриваются надежные, обоснованные решения, которые не вступают в противоречие с концептуальными.

BACKGROUND:Ionizing Radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in rodents can be inferred by alterations of a psycho- emotional balance, primarily an anxiogenic effect of IR. In our recent work, we hypothesized that the neurokinin-1 (NK1) receptor might be instrumental for such alterations.OBJECTIVE:The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected to test this hypothesis on Wistar rats.METHODS:Pharmacological substances were administered through intragastric probes. We used a battery of tests for a comprehensive ethological analysis. High-performance liquid chromatography was applied to quantify monoamines content. An analysis of mRNA expression was performed by real-time PCR. Protein content was studied by the Western blotting technique.RESULTS:Our salient finding includes no substantial changes in anxiety, locomotor activity and cognitive abilities of treated rats under irradiation. No differences were found in the content of monoamines. We discovered a synchronous effect on mRNA expression and protein content of 5- HT2a and 5-HT4 receptors in the prefrontal cortex, as well as decreased content of serotonin transporter and increased content of tryptophan hydroxylase in the hypothalamus of irradiated rats. Rolapitant affected the protein amount of a number of serotonin receptors in the amygdala of irradiated rats.CONCLUSION:Rolapitant may be the first atypical radioprotector, providing symptomatic treatment of CNS functional disorders in astronauts caused by IR.