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The effective study of Computer Science is impossible without the widespread use of information technology. Boolean algebra is one of the most fundamental sections of computer science. There is a list of disadvantages of this testing method for the evaluation of the master’s degree students’ knowledge of this topic. This results in development of other interactive tools. This article is devoted to the development and operation features of the automated system “Boolean algebra”, which was designed to control the formation of the competencies’ achievement indicators obtained during studying Boolean algebra. The developed system automatically creates task option and contains three types of tasks. The frst task includes construction of a truth table for three Boolean functions, the second requires Boolean circuit construction, and the third task is focused on Boolean expression simplifying. The system architecture consists of eightindependent modules which realize the new task option synthesis and its design, Boolean functions decomposition, truth tables construction, analysis, and evaluation of the results. The article describes the concept of each module. It describes in detail the synthesis of Boolean functions, as well as the analysis modules and their functioning algorithms. The automated system under operation proved to be effective since it allows one to objectively evaluate user’s theoretical knowledge and ability to apply these methods to the truth tables construction. There are also several advantages of the considered automated system: it requires little space on a hard disk, workes in a network and on local computer, has intuitive interface, generates a large variety of tasks and performs their autocheking.

It is well-established that double-stranded RNA (dsRNA) exhibits noticeable radioprotective and radiotherapeutic effects. The experiments conducted in this study directly demonstrated that dsRNA was delivered into the cell in its native form and that it induced hematopoietic progenitor proliferation. The 68 bp synthetic dsRNA labeled with 6-carboxyfluorescein (FAM) was internalized into mouse hematopoietic progenitors, c-Kit+ (a marker of long-term hematopoietic stem cells) cells and CD34+ (a marker of short-term hematopoietic stem cells and multipotent progenitors) cells. Treating bone marrow cells with dsRNA stimulated the growth of colonies, mainly cells of the granulocyte–macrophage lineage. A total of 0.8% of Krebs-2 cells internalized FAM-dsRNA and were simultaneously CD34+ cells. dsRNA in its native state was delivered into the cell, where it was present without any signs of processing. dsRNA binding to a cell was independent of cell charge. dsRNA internalization was related to the receptor-mediated process that requires energy from ATP. Synthetic dsRNA did not degrade in the bloodstream for at least 2 h. Hematopoietic precursors that had captured dsRNA reinfused into the bloodstream and populated the bone marrow and spleen. This study, for the first time, directly proved that synthetic dsRNA is internalized into a eukaryotic cell via a natural mechanism.

The Black Sea is one of the main recreational facilities in Russia subject to a high annual anthropogenic stress. Anthropogenic activity led to high coastal sea waters pollution, eutrophy, and endangered the sea’s self-purification capabilities. The total quarantine introduced on the Black Sea coast of the Krasnodar territory associated with the new coronavirus infection COVID-19 pandemic led to a decrease in anthropogenic pressure on coastal ecosystems and provided a unique opportunity to trace the dynamics of the most important hydrochemical indicators of coastal waters in the Tuapse district. The study aimed to characterize the impact of quarantine measures against the coronavirus on the state of coastal waters in the eastern part of the Russian Black Sea. For this, we identified and characterized the hydrochemical indicators and determined the effect of quarantine measures on their dynamics. The study used the standardized methods. The results obtained showed that a decrease in the recreational stress led to a proportional decrease in the pollutants supply to coastal sea waters; with the recreational stress resumption the concentrations of mobile pollutants tended to increase; a proportional relationship was established between biochemical oxygen demand (BOD5 ) and the ammonium nitrogen (NH4+) concentration; the nitrates’ (NO3–) concentration, in the seawater did not depend on the recreational stress degree. In particular, a proportional increase in NH4+ concentration and BOD5 in seawater was detected: in the third quarter of 2019 the concentration of NH4+ and BOD5 amounted to 3.0 mg/dm3 and 8.5 mg/dm3 , and 3.8 mg/dm3 and 7.5 mg/dm3 in the fourth quarter, respectively; in the 2020 samples, a decrease in the NH4+ concentration to 0.8 mg/dm3 in the third and to 1.2 mg/dm3 in the fourth quarter led to a proportional decrease in BOD5 4.5 mg/dm3 and 3.9 mg/dm3 , respectively. Thus, it was shown that the quarantine measures were shown to have a positive effect on the processes of self-purification of coastal sea waters in recreational zones.

This paper discusses the issue of utilization of rice and buckwheat husks, a comparison of their modifying effect in epoxy antifriction coatings, for this, the elemental composition of these fillers was determined using X-ray fluorescence analysis, their structure was analyzed by scanning electron microscopy, and the acid-base characteristics of the filler surface were determined by the pH method., the surface area of the pores of the ash of rice and buckwheat husks, their oil absorption were calculated, a sol-gel analysis was carried out to assess the density of the spatial network of filled epoxy coatings, and their wear resistance and hardness were determined. In the course of the research, the optimal temperature for obtaining ash from rice and buckwheat husks was established, which contributes to an increase in wear resistance, hardness and a decrease in the static friction coefficient of filled epoxy coatings. It is shown that the optimal temperature for obtaining rice husk ash is 500 C, and buckwheat husk ash 800 C. At the same time, rice husk ash is a more effective filler for epoxy polymers than buckwheat husk ash, since it increases the hardness of materials and provides a greater decrease in their friction coefficient.

The article is devoted to the concept of an associative landscape and the phenomenon of the visual nature of its perception. The aim of the work is to study the sign-symbolic images of nature on the example of a cultural landscape and their visualization of graphic design. The article examines the features of associative landscapes, the semiotic concept of the cultural landscape and its semantic reading as a text, the concept of semiosphere and noosphere. The object of the research is the associative landscape as a special type of space perception based on a visual-semiotic language. The subject of the research is the cultural landscape as a visual-spatial category, expressed in sign-symbolic images and directly related to the natural environment.

В статье представлен опыт работы применения камешков Марблс в игровой деятельности с детьми дошкольного возраста.

At present the study of computer science is almost impossible imagine without electronic educational resources usage. These resources are most often represents at learning package. Synthesis of learning packages is labour and resource intensive process. The results of this process influence to students work efficient. Article is devoted to creating automated system synthesis of structured educational content. This system is the universal shell for computer science learning package. This system allow to unify educational process approach, apply regardless of course content, increase student work efficient in university local network. Developed system is include six independent module. These modules realize system load properties choose, service, system load, authentification and tools, student competence control. This article contains modules work concept. Module work concept of system load properties choose is describes in detail and it's function algorithm is presented. Educational content is structured to computer science teaching program. All content is divided to two logical section. Which section is contains several subsection. Those section and subsection are TreeView hierarchical tree nodes. They are included educational content elements by special algorithm. Universal test system and special developed on VBA interactive trainers are included to competence control subsection. Those trainers are program's which can generate task for several topic. The system which considering in this article have some advantages. It's occupied small memory on hard disk, it's worked in network and on local computer. The educational content can be flexible included in this system without on course volume and student basic knowledge level.

Background/aim We compared the therapeutic efficacy of two recently developed experimental anticancer technologies: 1) in situ vaccination based on local immunotherapy with CpG oligonucleotides and anti-OX40 antibodies to activate antitumor immune response and 2) "Karanahan" technology [from the Sanskrit kāraṇa ('source') + han ('to kill')] based on the combined injection of cyclophosphamide and double-stranded DNA to eradicate cancer stem cells. Materials and methods The anticancer approaches were compared on three types of mouse malignant tumors with different grades of immunogenicity: weakly immunogenic carcinoma Krebs-2, moderately immunogenic Lewis carcinoma, and highly immunogenic A20 В-cellular lymphoma. Results Our results indicated that in situ vaccination was the most effective against the highly immunogenic tumor А20. In addition, "Karanahan" demonstrated high efficiency in all types of tumors, regardless of their immunogenicity or size. Conclusion "Karanahan" therapy showed higher efficacy relative to in situ vaccination with CpG oligonucleotides and anti-OX40 antibodies.

Selenium is in many ways an enigmatic element. It is essential for health but toxic in excess, with the difference between the two doses being narrower than for any other element. Environmentally, selenium is of concern due to its toxicity. As the rarest of the essential elements, its low levels often provide challenges to the analytical chemist. X-ray absorption spectroscopy (XAS) provides a powerful tool for in situ chemical speciation but is severely limited by poor spectroscopic resolution arising from core-hole lifetime broadening. Here we explore selenium Kα1 high energy resolution fluorescence detected XAS (HERFD-XAS) as a novel approach for chemical speciation of selenium, in comparison with conventional Se K-edge XAS. We present spectra of a range of selenium species relevant to environmental and life science studies, including spectra of seleno-amino acids, which show strong similarities with S K-edge XAS of their sulfur congeners. We discuss strengths and limitations of HERFD-XAS, showing improvements in both speciation performance and low concentration detection. We also develop a simple method to correct fluorescence self-absorption artifacts, which is generally applicable to any HERFD-XAS experiment.

This article is the second communication in a series of articles devoted to the effects of a domestic preparation of macrophage-activating factor (GcMAF-RF) and assessment of its biological properties. The aim of this work was to study the effect of the GcMAF-RF upon M0 → M1 polarization of macrophages (Mph), and activation of the professional properties of ex vivo generated antigen-presenting dendritic cells (DC), as well as on ex vivo production of pro-inflammatory (TNFα, IL-1β, IL-6, IFNγ, IL-17, IL-18) and anti-inflammatory (TGF-β, IL-4, IL-10) cytokines, growth factors (IL-2, GM-CSF, G-CSF, VEGF) and chemokines (MCP, IL-8) by the whole blood cells from healthy donors. Mph and DC were generated from the monocytes (3 to 5×106 /ml) derived from adherent fraction of peripheral blood mononuclear cells (MNC) of healthy donors. Granulocyte/macrophage colony-stimulating factor (rhGM-CSF) was used to obtain Mph, whereas DC production was induced by GM-CSF and interferon-α. To provide M1 polarizing signals, bacterial lipopolysaccharide (LPS from E. coli 0114:B4) was used in controls. In experimental series, GcMAF-RF was added 48 h before the end of culture. The stimulating effect of the obtained Mph and DC upon cell proliferation was assessed in allogeneic mixed culture of leukocytes (alloMLC) using radiometric technique, by 3 H-thymidine incorporation. The influence index (IR) of Mph or DC upon allo-SCL was calculated as the ratio of the proliferative response of MNCs in the presence of Mph, or DC to the level of spontaneous MNC proliferation. To determine the cytokine production by human whole blood cells ex vivo, peripheral blood samples from 3 donors with two replicate GcMAF-RF preparations were used, at a total of 6 points. All variants of the study were carried out with mitogen-activated and non-activated blood cells. The cytokine content was determined by the ELISA assays. The effects of GcMAF-RF were quantified as a fold increase (FI), i.e., the ratio of cytokine production in the presence of GcMAF-RF to the level of their spontaneous production. It was shown that the GcMAF-RF preparation was as effective, as lipopolysaccharide (LPS), the standard Mph and DC activator which induces polarization of differentiated M0-macrophages into M1 cells and final maturation of DCs, manifesting by a significant increase in their allo-stimulatory activity in a mixed leukocyte culture (allo-MLC). Moreover, GcMAF-RF stimulates production of numerous cytokines and chemokines (TNFα, IL-1β, IL-6, IL-18, IL-4, IL-10, GM-CSF, G-CSF, VEGF, IL-8), by blood cells (granulocytes, lymphocytes, monocytes), thus indicating direct participation of the macrophage activator GcMAF-RF in various immune processes. The domestic GcMAF-RF drug induces polarization of macrophages M0 → M1, final maturation of DCs and allostimulating activity of Mf and DCs, and is also able to effectively stimulate circulating blood cells to synthesize cytokines/chemokines with pro-inflammatory and immunoregulatory activities.

Although Alzheimer’s disease (AD) was first described over a century ago, it remains the leading cause of age-related dementia. Innumerable changes have been linked to the pathology of AD; however, there remains much discord regarding which might be the initial cause of the disease. The “amyloid cascade hypothesis” proposes that the amyloid beta (Aβ) peptide is central to disease pathology, which is supported by elevated Aβ levels in the brain before the development of symptoms and correlations of amyloid burden with cognitive impairment. The “metals hypothesis” proposes a role for metal ions such as iron, copper, and zinc in the pathology of AD, which is supported by accumulation of these metals within amyloid plaques in the brain. Metals have been shown to induce aggregation of Aβ and metal ion chelators have been shown to reverse this reaction in vitro. 8-Hydroxyqinoline-based chelators showed early promise as anti-Alzheimer’s drugs. Both 5-chloro-7-iodo-8-hydroxyquinoline (CQ) and 5,7-dichloro-2[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2) underwent unsuccessful clinical trials for the treatment of AD. To gain insight into the mechanism of action of 8HQs, we have investigated the potential interaction of CQ, PBT2, and 5,7-dibromo-8-hydroxyquinoline (B2Q) with Cu(II)-bound Aβ(1-42) using X-ray absorption spectroscopy (XAS), high energy resolution fluorescence detected (HERFD) XAS, and electron paramagnetic resonance (EPR). By XAS, we found CQ and B2Q sequestered ~83% of the Cu(II) from Aβ(1-42), whereas PBT2 sequestered only ~59% of the Cu(II) from Aβ(1-42), suggesting that CQ and B2Q have a higher relative Cu(II) affinity than PBT2. From our EPR, it became clear that PBT2 sequestered Cu(II) from a heterogeneous mixture of Cu(II)Aβ(1-42) species in solution leaving a single Cu(II)Aβ(1-42) species. It follows that the Cu(II) site in this Cu(II)Aβ(1-42) species is inaccessible to PBT2 and may be less solvent-exposed than in other Cu(II)Aβ(1-42) species. We found no evidence to suggest that these 8HQs form ternary complexes with Cu(II)Aβ(1-42).

Until recently, sulfur was known as a "spectroscopically silent" element because of a paucity of convenient spectroscopic probes suitable for in situ chemical speciation. In recent years the technique of sulfur K-edge X-ray absorption spectroscopy (XAS) has been used extensively in sulfur speciation in a variety of different fields. With an initial focus on reduced forms of organic sulfur, we have explored a complementary X-ray based spectroscopy - sulfur Kβ X-ray emission spectroscopy (XES) - as a potential analytical tool for sulfur speciation in complex samples. We compare and contrast the sensitivity of sulfur Kβ XES with that of sulfur K-edge XAS, and find differing sensitivities for the two techniques. In some cases an approach involving both sulfur K-edge XAS and sulfur Kβ XES may be a powerful combination for deducing sulfur speciation in samples containing complex mixtures.

A small-sized laboratory unit has been designed and manufactured for laboratory research of the process of cleaning gas emissions from phosphorus particles in a foam absorber. The installation is designed in accordance with the requirements of the similarity theory, which allows you to fully simulate the processes occurring in an industrial installation. The use of a small-sized laboratory foam filtration unit at the research stage will optimize and reduce the cost of the process of developing an industrial gas cleaning unit.

Price is the most important tool of company behavior on market, whose changes are caught immediately by customers, competitors and state structures. Adequate pricing can bring profit to the company and raise its competitiveness and stability on market. Unfortunately, rather often price decisions of home exporters working on non-raw material markets are only a response to competitors’ steps and they aim at reaching tactical, momentary but not strategic goals. Companies usually try to use the same price strategies on foreign markets as they use on national market. In conditions of the global crisis, uneven introduction of isolation regime and border closing by countries, breaking supply chains, bankruptcy or closure of national companies Russian exporters face the loss of distribution channels developed earlier. On the other hand, in these conditions they get an opportunity not only to settle on developed markets nut to penetrate new overseas markets in such segments, where the work of local companies was cut or shut down. In any case home exporters should think over their price strategy on foreign market and research changes in customer preferences, in their perception of company product value. The author gives recommendations aimed at improving exporters’ pricing in conditions of 2020 crisis on the basis of analyzing customers in view of their contribution to the company profit.

Here, we report on ultrafast all-optical modulation of the surface-plasmon (SP)-assisted transverse magneto-optical Kerr effect (TMOKE) and the reflectance in a one-dimensional nickel magnetoplasmonic crystal (MPC). A 50 fs nonresonant laser pump pulse with 7 mJ/cm2 fluence reduces the magnetization by 65%, which results in the suppression of TMOKE in the SP-resonant probe from 1.15% to 0.4%. The differential reflectance of SP-resonant probe achieves 5.5%. Besides this, it is shown that electron thermalization and relaxation in MPC are several times slower than those in the plane nickel.

8-Hydroxyquinolines (8HQs) comprise a family of metal-binding compounds that have been used or tested for use in numerous medicinal applications, including as treatments for bacterial infection, Alzheimer's disease, and cancer. Two key 8HQs, CQ (5-chloro-7-iodo-8-hydroxyquinoline) and PBT2 (2-(dimethylamino)methyl-5,7-dichloro-8-hydroxyquinoline), have drawn considerable interest and have been the focus of many studies investigating their in vivo properties. These drugs have been described as copper and zinc ionophores because they do not cause metal depletion, as would be expected for a chelation mechanism, but rather cellular accumulation of these ions. In studies of their anti-cancer properties, CQ has been proposed to elicit toxic intracellular copper accumulation and to trigger apoptotic cancer cell death through several possible pathways. In this study we used synchrotron X-ray fluorescence imaging, in combination with biochemical assays and light microscopy, to investigate 8HQ-induced alterations to metal ion homeostasis, as well as cytotoxicity and cell death. We used the bromine fluorescence from a bromine labelled CQ congener (5,7-dibromo-8-hydroxyquinoline; B2Q) to trace the intracellular localization of B2Q following treatment and found that B2Q crosses the cell membrane. We also found that 8HQ co-treatment with Cu(ii) results in significantly increased intracellular copper and significant cytotoxicity compared with 8HQ treatments alone. PBT2 was found to be more cytotoxic, but a weaker Cu(ii) ionophore than other 8HQs. Moreover, treatment of cells with copper in the presence of CQ or B2Q resulted in copper accumulation in the nuclei, while PBT2-guided copper was distributed near to the cell membrane. These results suggest that PBT2 may be acting through a different mechanism than that of other 8HQs to cause the observed cytotoxicity.

Demyelination and oligodendrocyte loss are characteristic changes in demyelinating disorders. Low-field magnetic stimulation (LFMS) is a novel transcranial neuromodulation technology that has shown promising therapeutic potential for a variety of neuropsychiatric conditions. The cellular and molecular mechanisms of magnetic stimulation remain unclear. Previous studies mainly focused on the effects of magnetic stimulation on neuronal cells. Here we aimed to examine the effects of a gamma frequency LFMS on the glial progenitor cells. We used rat central glia-4 (CG4) cell line as an in vitro model. CG4 is a bipotential glial progenitor cell line that can differentiate into either oligodendrocyte or type 2-astrocyte. The cells cultured in a defined differentiation media were exposed to a 40-Hz LFMS 20 min daily for five consecutive days. We found that LFMS transiently elevated the level of TGF-β1 in the culture media in the first 24 h after the treatment. In correlation with the TGF-β1 levels, the percentage of cells possessing complex branches and expressing the late oligodendrocyte progenitor marker O4 was increased, indicating the accelerated differentiation of CG4 cells towards oligodendrocyte in LFMS-treated cultures. LFMS increased phosphorylation of Akt and Erk1/2 proteins, but not SMAD2/3. TGF-β1 receptor I specific inhibitor LY 364947 partially suppressed the effects of LFMS on differentiation and on levels of pAkt and pErk1/2, indicating that LFMS enhances the differentiation of oligodendrocyte progenitor cells via activation of non-canonical TGF-β-Akt and TGF-β-Erk1/2 pathways but not the canonical SMAD pathway. The data from this study reveal a novel mechanism of magnetic stimulation as a potential therapy for demyelination disorders.

The article reports an original method for producing vitamin D3-binding protein (DBP) and its conversion into macrophage-activating factor GcMAF-RF. According to an original protocol, DBPs were obtained from human blood plasma using affinity chromatography, purified and modified to GcMAF-RF using cytoimmobilized glycosidases (beta-galactosidase and neuraminidase). The presence of the polypeptide obtained in the Gc group of blood plasma globulins was confirmed by Western blot using specific antibodies. The molecular properties of this polypeptide put it in correspondence with the GcMAF protein described in the literature, which is undergoing clinical trials in the USA, Britain, Israel and Japan (at Saisei Mirai; Reno Integrative Medical Center; Immuno Biotech Ltd; Efranat; and Catalytic Longevity). The biological activity of the GcMAF-RF preparation was detected by the induction of phagocytic activity of macrophages and their ability to produce nitrogen monoxide (NO) in vitro.The phagocytic activity of macrophages was evaluated by their ability to uptake magnetic beads. The degree of activation of macrophages was calculated by the ratio of trapped beads to the total number of macrophages. The level of NO production was estimated by the accumulation of nitrogen monoxide in the culture supernatants of peritoneal macrophages by the colorimetric method using the Griess reagent. It was shown that GcMAF-RF multiplies the phagocytic activity of macrophages and significantly increases their production of nitrogen monoxide. The macrophage activator GcMAF-RF, according to its characteristics, corresponds to similar preparations which are made available to the market by foreign companies, and can be considered as a new biologically active preparation with a wide spectrum of action. Of greatest interest is its ability - through the activation of macrophages - to enhance the adaptive immunity. In this regard, two areas of therapeutic use of the GcMAF-RF are proposed. The preparation will be in demand in the field of cancer treatment, and, in addition, it can be used in the treatment of a number of neurodegenerative pathologies.

The main problem related to the studies focusing on group-specific component protein-derived macrophage-activating factor (GcMAF) is the lack of clarity about changes occurring in different types of macrophages and related changes in their properties under the effect of GcMAF in various clinical conditions. We analyzed the antitumor therapeutic properties of GcMAF in a Lewis carcinoma model in two clinical conditions: untreated tumor lesion and tumor resorption after exposure to Karanahan therapy. GcMAF is formed during site-specific deglycosylation of vitamin D3 binding protein (DBP). DBP was obtained from the blood of healthy donors using affinity chromatography on a column with covalently bound actin. GcMAF-related factor (GcMAF-RF) was converted in a mixture with induced lymphocytes through the cellular enzymatic pathway. The obtained GcMAF-RF activates murine peritoneal macrophages (p < 0.05), induces functional properties of dendritic cells (p < 0.05) and promotes in vitro polarization of human M0 macrophages to M1 macrophages (p < 0.01). Treatment of whole blood cells with GcMAF-RF results in active production of both pro- and anti-inflammatory cytokines. It is shown that macrophage activation by GcMAF-RF is inhibited by tumor-secreted factors. In order to identify the specific antitumor effect of GcMAF-RF-activated macrophages, an approach to primary reduction of humoral suppressor activity of the tumor using the Karanahan therapy followed by macrophage activation in the tumor-associated stroma (TAS) was proposed. A prominent additive effect of GcMAF-RF, which enhances the primary immune response activation by the Karanahan therapy, was shown in the model of murine Lewis carcinoma. Inhibition of the suppressive effect of TAS is the main condition required for the manifestation of the antitumor effect of GcMAF-RF. When properly applied in combination with any chemotherapy, significantly reducing the humoral immune response at the advanced tumor site, GcMAF-RF is a promising antitumor therapeutic agent that additively destroys the pro-tumor properties of macrophages of the tumor stroma.

Mercury is ubiquitous in the environment, with rising levels due to pollution and climate change being a current global concern. Many mercury compounds are notorious for their toxicity, with the potential of organometallic mercury compounds for devastating effects on the structures and functions of the central nervous system being of particular concern. Chronic exposure of human populations to low levels of methylmercury compounds occurs through consumption of fish and other seafood, although the health consequences, if any, from this exposure remain controversial. We have used high energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) to determine the speciation of mercury and selenium in human brain tissue. We show that the molecular fate of mercury differs dramatically between individuals who suffered acute organometallic mercury exposure (poisoning) and individuals with chronic low-level exposure from a diet rich in marine fish. For long-term low-level methylmercury exposure from fish consumption, mercury speciation in brain tissue shows methylmercury coordinated to an aliphatic thiolate, resembling the coordination environment observed in marine fish. In marked contrast, for short-term high-level exposure we observe the presence of biologically less-available mercuric selenide deposits, confirmed by X-ray fluorescence imaging, as well as mercury(II)-bis-thiolate complexes, which may be signatures of severe poisoning in humans. These differences between low-level and high-level exposures challenge the relevance of studies involving acute exposure as a proxy for low-level chronic exposure.

Mercury is in some sense an enigmatic element. The element and some of its compounds are a natural part of the biogeochemical cycle; while many of these can be deadly poisons at higher levels, environmental levels in absence of anthropogenic contributions would generally be below the threshold for concern. However, mercury pollution, particularly from burning fossil fuels such as coal, is providing dramatic and increasing emissions into the environment. Because of this the environmental chemistry and toxicology of mercury is of growing importance, with the fate of mercury being vitally dependent upon its speciation. X-ray absorption spectroscopy (XAS) provides a powerful tool for in situ chemical speciation, but is severely limited by poor spectroscopic energy resolution. Here, we provide a systematic examination of mercury Lα1 high energy resolution fluorescence detected XAS (HERFD-XAS) as an approach for chemical speciation of mercury, in quantitative comparison with conventional Hg L(III)-edge XAS. We show that, unlike some lighter elements, chemical shifts in the Lα1 X-ray fluorescence energy can be safely neglected, so that mercury Lα1 HERFD-XAS can be treated simply as a high-resolution version of conventional XAS. We present spectra of a range of mercury compounds that may be relevant to the environmental and life science research, and show that density functional theory can produce adequate simulations of the spectra. We discuss strengths and limitations of the method, and quantitatively demonstrate improvements both in speciation for complex mixtures and in background rejection for low concentrations.

Статья посвящена проблеме качества гуманитарного образования в непрофильных вузах при переходе к новым образовательным стандартам в условиях изменения культурно-информационной среды и формирования клипового сознания.

В статье рассматривается модернизация как процесс социальных изменений, происходящих в современном обществе. Проводится социально-философский анализ различных концепций, изучающих категорию «социальная модернизация». Подчеркивается значимость преемственности как органичного и субстанционального аспекта модернизации.

The current coronavirus pandemic is exerting a tremendously detrimental impact on global health. The Spike proteins of coronaviruses, responsible for cell receptor binding and viral internalization, possess multiple and frequently conserved disulfide bonds raising the question about their role in these proteins. Here, we present a detailed structural and functional investigation of the disulfide bonds of the SARS-CoV-2 Spike receptor-binding domain (RBD). Molecular dynamics simulations of the RBD predict increased flexibility of the surface loops when the four disulfide bonds of the domain are reduced. This flexibility is particularly prominent for the disulfide bond-containing surface loop (residues 456-490) that participates in the formation of the interaction surface with the Spike cell receptor ACE2. In vitro, disulfide bond reducing agents affect the RBD secondary structure, lower its melting temperature from 52 °C to 36-39 °C and decrease its binding affinity to ACE2 by two orders of magnitude at 37 °C. Consistent with these in vitro findings, the reducing agents tris(2-carboxyethyl)phosphine (TCEP) and dithiothreitol (DTT) were able to inhibit viral replication at low millimolar levels in cell-based assays. Our research demonstrates the mechanism by which the disulfide bonds contribute to the molecular structure of the RBD of the Spike protein, allowing the RBD to execute its viral function.

Selenoenzymes, containing a selenocysteine (Sec) residue, fulfill important roles in biology. The mammalian thioredoxin reductase selenoenzymes are key regulators of antioxidant defense and redox signaling and are inhibited by methylmercury species and by the gold-containing drug auranofin. It has been proposed that such inhibition is mediated by metal binding to Sec in the enzyme. However, direct structural observations of these classes of inhibitors binding to selenoenzymes have been few to date. Here we therefore have used extended X-ray absorption fine structure as a direct structural probe to investigate binding to the selenium site in recombinant rat thioredoxin reductase 1 (TrxR1). The results demonstrate for the first time the direct and complete binding of the metal atom of the inhibitors to the selenium atom in TrxR1 for both methylmercury and auranofin, indicating that TrxR1 inhibition indeed can be attributed to such direct metal-selenium binding.

Background/aim We previously have described the "3+1" tumors cure approach consisting of individual time schedule of cyclophosphamide and dsDNA preparation administrations. The aim of the study was to adapt the "3+1" approach based on eradication of cancer stem cells to the model of murine ascitic cyclophosphamide-resistant lymphosarcoma (RLS). Materials and methods Adaptation of the "3+1" approach includes the identification of the timing to disrupt the tumorigenic potential of a certain tumor. Results The proposed therapeutic scheme allowed complete reduction of primary RLS ascites in experimental animals. However, reduction of primary ascites due to the complementary action of cyclophosphamide and dsDNA was inevitably followed by the development of a secondary one, most likely arising from a solid carcinomatous formation in the peritoneal wall. Conclusion The "3+1" approach resulted in the elimination of cancer stem cells, and, as a consequence, in the complete reduction of RLS ascites.

Industrial release of mercury into the local Minamata environment with consequent poisoning of local communities through contaminated fish and shellfish consumption is considered the classic case of environmental mercury poisoning. However, the mercury species in the factory effluent has proved controversial, originally suggested as inorganic, and more recently as methylmercury species. We used newly available methods to re-examine the cerebellum of historic Cat 717, which was fed factory effluent mixed with food to confirm the source. Synchrotron high-energy-resolution fluorescence detection-X-ray absorption spectroscopy revealed sulfur-bound organometallic mercury with a minor β-HgS phase. Density functional theory indicated energetic preference for α-mercuri-acetaldehyde as a waste product of aldehyde production. The consequences of this alternative species in the "classic" mercury poisoning should be re-evaluated.

The paper discusses the development of an expert system for diagnosing electric traction motors of rolling stock. The diagnostic parameters of the electric traction motor commutator-and-brush assembly, being the input linguistic variables of the fuzzy model, were selected with the use of graphoanalytic model. A fuzzy mathematical model and a fuzzy neural network for comprehensive indicator of quality of mechanical machining implementing the Takagi — Sugeno fuzzy inference algorithm were developed. The authors confirmed the practicability and the adequacy of the previously proposed comprehensive indicator of quality of mechanical machining for assessing the technical condition of the electric traction motor commutator-and-brush assembly. The studies carried out allowed creating an element of intelligent expert diagnostics system that enables a comprehensive assessment of technical condition of electric traction motor.