Aim. The purpose of the work was the development of a machine learning model for diagnosing the stage of liver fibrosis in patients with chronic viral hepatitis C according to the data of routine clinical examination. Materials and methods. A total of 1240 patients with chronic viral hepatitis C was examined. A set of data obtained from 689 patients balancing by the stage of liver fibrosis was used for developing and testing machine learning models. 9 routine clinical parameters were selected as the most important predictors for determining the likelihood of liver fibrosis the 3–4 stages presence: age, height, weight and body mass index of the patient, the number of platelets in the clinical blood test, levels of alanine transaminase, aspartate transaminase, gamma-glutamyltransferase, and total bilirubin in a biochemical blood test. Results. The accuracy of the developed method for determining the 3–4 stages of liver fibrosis in patients with chronic viral hepatitis C in comparison with the «gold standard» of diagnosis (liver biopsy) was 80.56% (95% CI: 69.53–88.94%), sensitivity — 66.67%, specificity — 94.44%. Conclusion. The developed method is an alternative to more expensive and geographically inaccessible studies. The method does not require the purchase of additional equipment or software, as well as additional laboratory tests, when used in real clinical practice. The introduction of the method into clinical practice can help to solve the problem of low material and territorial availability of diagnostic tests and allow determining the stage of liver fibrosis in patients with chronic viral hepatitis C.

In the paper, the results of an investigation into trace elements found in slag sulphides from 14 archaeological Bronze Age settlements of the Cis-Urals, Trans-Urals and North and Central Kazakhstan are presented. The study used Cu-(Fe)-sulphides as indicator minerals. Cu-(Fe)-S minerals in slags are primarily represented by covellite and chalcocite, as well as by rarer bornite and single chalcopyrite grains. Slag sulphides formed relic clasts and neogenic droplets of different shapes and sizes. Supergenic ores in the Bronze Age in Urals and Kazakhstan played a significant role in the mineralogical raw material base. In sulphides, the main indicator elements Fe, Co, Ni, As, Se, Te, Sb, Ag, Pb, and Bi are important markers of copper deposit types. Sulphides from olivine Cr-rich spinel containing slags of Ustye, Turganik, and Kuzminkovskoe 2 are characterised by As-Co-Ni assemblages and confined to copper deposits in ultramafic rocks. Olivine sulphide-containing slags from Kamenny Ambar, Konoplyanka and Sarlybay 3 are characterised by Co-Se-Te assemblage and confined to mafic rocks. Glassy sulphide-containing slags from Katzbakh 6, Turganik, Ordynsky Ovrag, Ivanovskoe, Tokskoe, Bulanovskoe 2, Pokrovskoe, Rodnikovoe, and Taldysay are characterised by Ag-Pb-(Ba)-(Bi) assemblage and confined to cupriferous sandstone deposits. High As, Sb, Sn and Ba contents found in slags can be seen as indicators of alloying or flux components in primary copper smelting. These include samples from Ustye, Katzbakh 6, Rodnikovoe, and Taldysay sites, where high Ba and As slag contents are identified. The compilation of a database with a broad sample of sulphide compositions from Bronze Age slags and mines in the Urals and Kazakhstan will permit the further identification of ore types and raw materials associated with a particular deposit.

Features of nanosecond discharge development in a non-uniform electric field are studied experimentally. High spatial resolution imaging showed that thin luminous tracks of great length with a cross-section of a few microns are observed against the background of discharge glow in air and argon. It has been established that the detected tracks are adjacent to brightly luminous white spots on the electrodes or to the vicinity of these spots, and are associated with the flight of small particles. It is shown that the traces have various shapes and change from pulse to pulse. The particle tracks may look like curvy or straight lines. In some photos, they can change the direction of movement to the opposite. The particle trace was found to abruptly cut off and a bright flash is visible at the trail break point. The color of the tracks differs from that of the spark leaders, while the bands of the second positive nitrogen system dominate in the gap spectra during the existence of a diffuse discharge. Areas of blue light are evident near the electrodes, as well. Development of glow in the gap during its breakdown is revealed using an ICCD camera. Physical reasons for the observed phenomena are discussed.

In a saline semi-isolated Lagoon on the Cape Zeleny (White Sea), the annual dynamics of the vertical hydrological structure, and the seasonal dynamics of phytoplankton were traced, including species composition, and vertical distribution, abundance, nutrition type,and biomass.293 species and supraspecific taxa of algae and cyanobacteria were found. Most of the identified species are marine, and 38 species are freshwater. Taxonomic composition changed in the Lagoon during the year. Dinoflagellates dominated in winter and early June; unidentified cocci and flagellates in July; diatoms, dinoflagellates and unidentified cells in August; dinoflagellates in September; and unidentified cocci and flagellates in October–November. The abundance of algae also changed in the Lagoon during the year. The integrated biomass in the water column varied from 0.01 g C/m2 in January to 0.78 g C/m2 in early September. According to the abiotic parameters, the water column of the Lagoon is subdivided into several zones with different conditions and corresponding phytoplankton communities. Similarity between the communities of different horizons was 32-46% in summer and 7% in winter. The chemocline layer was the most populous. Almost the entire year it contained a maximum of phytoplankton biomass, 1-2 orders of magnitude higher than that in the overlying horizons. Comparison phytoplankton in the lagoon and in the nearby sea area was carried out. Despite the connection between the Lagoon and the sea phytoplankton structure in the surface water layer in the Lagoon and in the sea differs significantly in composition, quantitative parameters, and seasonal dynamics. The similarity of the communities in the sea and the Lagoon never exceeded 50%. In terms of biomass, the Lagoon lags behind the sea until mid-summer, but, starting from August, it outnumbers it, and the phytoplankton development in the Lagoon lasts longer, until late autumn. The phytoplankton structure and dynamics in the Lagoon and the sea by 24.5% was related to the daylight, water salinity, oxygen content and pH, but did not depend on water T, underwater illuminance, and depth. Oxygen content and pH are defined by PhP activity. Salinity serves as a vector of the vertical sequence of ecological niches. The daylight length seems to be the crucial factor of the seasonal PhP dynamics in the semi-isolated coastal stratified lakes and lagoons.

Reliable species identification is critical for detection and monitoring of biological invasions. In this study, we propose four sets of primers for efficient amplification of several loci, including the mitochondrial cytochrome oxidase-c (COI) subunit I gene which is a basis for DNA barcoding. This set of primers gives a shorter product which can be used in high-throughput sequencing systems for metabarcoding purposes. Another mitochondrial locus encoding the large ribosomal subunit (16S) may be useful to study the population structure and as an additional source of information in the metabarcoding of communities. We propose to use a set of primers for the nuclear locus of the small ribosomal subunit (18S) as a positive control and to verify the results of the barcoding. Our proposed sets of primers demonstrate a high amplification efficiency and a high specificity both for freshwater alien and indigenous fishes. The proposed research design makes it possible to carry out extremely cheap studies on the assessment of biological diversity using genetic analysis without expensive equipment, and with the technique for conducting laboratory work and processing of the results available to any researcher. The paper also presents original data on the genetic polymorphism of all mass alien fish species in the Volga-Kama region. High efficiency of DNA identification based on our primers is shown as compared to traditional monitoring of biological invasions.

Abstract: The objective of these studies was to determine the dependence of the distribution of the microwave field into a grain layer and the efficiency of energy transfer from the magnetron into the grain layer, via a waveguide, on the moisture content. The subject of the research was a semicircular waveguide with slot radiators that supply a microwave field to the grain surrounding the waveguide. The change in the directional diagram of the microwave field in the longitudinal direction of the waveguide was studied using CST Microwave Studio 2019 software. It was found that the change in the moisture content of the processed grain leads to a significant change in both the radiation and total efficiency values of the waveguide. For instance, the radiation efficiency of the waveguide decreases by 15.1% (from 68.729 dB to 58.294 dB) when the moisture content of the processed grain increases from 14% to 26%. The total radiation efficiency also decreases (from 11.27 dB to 21.7 dB). In this case, not only the value of the radiation efficiency but also the shape of its dependence on the magnetron radiation frequency change. Data were obtained on the change in the Q-factor for resonators in which grain layers are processed, depending on the variation in grain moisture content.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

The qualitative analysis of nanodiamonds by FTIR spectrometry as photoacoustic (PAS), diffuse-reflectance (DRIFT), and attenuated total reflection (ATR) modalities was evaluated for rapid and nondestructive analysis and comparison of nanodiamonds. The spectra reproducibility and signal-gathering depth was compared. The assignment of characteristic bands showed that only six groups of bands were present in spectra of all the modalities with appropriate sensitivity: 1760 (C=O stretch, isolated carboxyl groups); 1640–1632 (H–O–H bend, liquid water); 1400–1370 (non-carboxyl C–O–H in-plane bend and CH2 deformation); 1103 (non-carboxyl C–O stretch); 1060 (in-plane C–H bend, non-aromatic hydrocarbons and carbohydrates); and 940 cm–1 (out-of-plane carboxyl C–O–H bend). DRIFT provides the maximum number of bands and is capable of measuring hydrogen-bonded bands and CHX groups. ATR provides the good sensitivity for water and C–H/C–C bands in the range 2000–400 cm–1. PAS-FTIR reveals less bands than DRIFT but more intense bands than ATR-FTIR and shows the maximum sensitivity for absorption bands that do not appear in ATR-IR spectra and are expedient for supporting either DRIFT or PAS along with depth-profiling. Thus, all three modalities are required for full characterization of nanodiamonds surface functional groups.

The study is based on the results of long-term field studies, satellite and aerial data analysis. In the maximum of the Little Ice Age (LIA) 243 glaciers with a total area of 353.4 km2 were reconstructed. By the results of interpretation of Corona images by 1968 the number of glaciers increased (236), the total area reduced to 242 km2. In 2010 glaciation was represented by 237 glaciers with a total area of 201 km2. Thus, from the maximum of the LIA, the glaciation of the Tavan-Bogd mountains decreased by 43%, which is somewhat less than the neighboring glacial centers (Ikh-Turgen, Tsambagarav, Tsengel-Khayrkhan and Mongun-Taiga mountains). The probable cause is the predominance of larger glaciers relatively resistant to warming and higher altitudes. The effect of glacier size on their stability is supported by differences in the relative shrinkage of glaciers in different parts of the Tavan-Bogdo-Ola massif: the smallest decline occurred in the basins of the Tsagan-Gol (31.7%) and Sangadir (36.4%) rivers where the largest glaciers are located. On the contrary, on the lower periphery of the massif, where small glaciers predominate, the relative reduction was large (74-79%). On the background of the general retreat trend large valleys glaciers retreated faster in 1968-1977 and after 2010. In 1990-s the retreat was slow. After 2010 the glacial retreat was extremely fast. The retreat of glaciers in the last 50-60 years was caused by a trend towards a decrease in the amount of precipitation until the mid-1970s and a sharp warming in the 1990s and early 2000s.

A new variant of the SARS-CoV-2 Omicron BA.5 virus has displaced all previous variants of the virus around the world. Preliminary assessment of the effectiveness of drugs for the prevention and treatment of COVID-19 requires the availability of infection models in animals. In this study, we characterize the infection model SARS-CoV-2 Omicron BA.5 and its progeny sublineage BE.1 in hACE2-transgenic mice and in Syrian hamsters. Both sublineages turned out to be pathogenic for animals – the challenged animals showed weight loss, a high level of viral load and acute inflammation in the lungs. Part of BA.5-infected mice died after virus challenge, indicating that this virus variant is more pathogenic than the previous BA.1 variant but less pathogenic than Wuhan variant.

The results of experimental studies of ohmic conductivity degradation in the ensembles of nanostructured anatase bridges under long-term effect of direct current are presented. Stochastic sets of interelectrode partially conducting bridges consisting of close-packed anatase nanoparticles were formed by the seeding particles from drying aqueous suspensions on the surfaces of silica substrates with interdigital platinum electrodes. Multiple-run experiments at room temperature have shown that ohmic conductivity degradation in these systems is irreversible. It is presumably due to accumulated capture of conduction electrons by deep traps in anatase nanoparticles. The scaling analysis of voltage drops across the samples at the final stage of degradation gives a critical exponent for ohmic conductivity as 1.597. This value satisfactorily agrees with the reported model data for percolation systems. At an early stage of degradation, the spectral density of conduction current fluctuations wihin the frequency range of 0.01 Hz - 1 Hz decreases approximately as , while near the percolation threshold the decrease trend changes to . This transition is interpreted in terms of an increasing contribution of blockages and subsequent avalanche-like breakdowns of part of the local conduction channels in the bridges into electron transport near the percolation threshold.

The paper shows that it is possible to obtain reliable information on the dependence of radial distribution of longitudinal birefringence in glass cylindrical elements with radial distribution of refractive index (GRIN lenses) on the basis of transverse polarization tomography data of residual stresses. This does not require complicated procedures of sample preparation, as is necessary in the case of longitudinal translucency measurements. The approach developed was verified in the experiments with a set of different GRIN lenses formed with ion exchange technique, and the closeness of the data obtained from transversal and conventional longitudinal transmission measurements was demonstrated.

The ordered Ca3TaGa3Si2O14 and disordered La3Ga5SiO14 crystals of the lantangallium silicate family were grown by the Czochralski method. The independent coefficients of thermal expansion of crystals αc and αa were determined by X-ray powder diffraction based on the analysis of X-ray diffraction spectra measured in the temperature range of 25÷1000°C. It is shown that in the temperature range of 25÷800°C the thermal expansion coefficients are linear. At temperatures above 800°C there is a nonlinear character of the thermal expansion coefficients associated with a decrease in the Ga content in the crystal lattice of the lantangallium silicate family crystals.

The generalized dual-kinetic-balance approach for axially symmetric systems is employed to solve the two-center Dirac problem. The spectra of one-electron homonuclear quasimolecules are calculated and compared with the previous calculations. The analysis of the monopole approximation with two different choices of the origin is performed. Special attention is paid to the lead and xenon dimers, Pb82+–Pb82+–e− and Xe54+–Xe54+–e−, where the energies of the ground and several excited σ-states are presented in the wide range of internuclear distances. The developed method provides the quasicomplete finite basis set and allows for construction of the perturbation theory, including within the bound-state QED.

It has long been known that phytohormone auxin plays a promoting role in tuber formation and stress tolerance in potatoes. Our study aimed to identify and characterize the complete sets of auxin-related genes that presumably constitute the entire auxin signaling system in potato (Solanum tuberosum L.). The corresponding genes were retrieved from sequenced genomes of the doubled monoploid S. tuberosum DM1-3-516-R44 (DM) of the Phureja group, the heterozygous diploid line RH89-039-16 (RH), and the autotetraploid cultivar Otava. Both canonical and noncanonical auxin signaling pathways were considered. Phylogenetic and domain analyzes of deduced proteins were supplemented by their expression profiling and 3D molecular modeling. The canonical and ABP1-mediated pathways of auxin signaling appeared to be well conserved. Total number of potato genes/proteins presumably involved in canonical auxin signaling is 46 and 108 in monoploid DM and tetraploid Otava, respectively. Among studied potatoes, spectra of expressed genes obviously associated with auxin signaling were partly cultivar-specific and quite different from analogous spectrum in Arabidopsis. Most of the noncanonical pathways found in Arabidopsis appeared to be low probable in potato. This was equally applied to all cultivars used irrespective of their ploidy. Thus, some important features of the (noncanonical) auxin signaling pathways may be variable and species-specific.

The microwave field is used for drying and disinfection of grain, during pre-sowing seed treat-ment. The use of a microwave field in these installations leads to an increase in their productivity and a decrease in the energy consumed by them. One of the principal problems of microwave field use for treatment of dense grain layers is to insure sufficient distribution uniformity of the field. In this article, waveguide design options have been discussed that serve to introduce microwave radiation into the grain layer. Mathematical simulation of the electromagnetic field distribution was performed with the use of CST Microwave Studio software in order to evaluate and compare horn-type, rectangular and semicircular waveguides. The data on the standing wave ratio and radiation efficiency for these types of waveguides have been reported. Specific features of the microwave electromagnetic field distribution and radiation power in the output of those wave-guides have been described. Results of mathematical simulations enabled to make out that sem-icircular waveguides with slot-type radiators are preferable for processing dense grain layers.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), 21% septal reduction therapy. Sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3) and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63 and FLNC; thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p=0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; family studies on some rare variants enriched the worldwide knowledge in HCM.

Recently, more and more countries are entering the global race for university competitiveness. On the one hand, global rankings are a convenient tool for quantitative analysis. On the other hand, their indicators are often difficult to quickly calculate, they often contradict each other. We thought about using widely available indicators for a quick analysis of the University's publication strategy. We opted for the normalized citation indicators available in SciVal analytical tool, i.e. Source Normalized Impact per Paper (SNIP) and Field-Weighted Citation Impact (FWCI). We have demonstrated the possibility of applying the correlation analysis to the impact indicators of a document and a journal on the sample of the social and humanitarian fields at Peoples' Friendship University of Russia. Particular attention was paid to the application of the results in practice.

The sensitivity of exercise ECG is marginally sufficient for detection of mild reduction of coronary blood flow in patients with early coronary atherosclerosis. Here we describe the application of new technique of ECG registration/analysis – ultrahigh resolution ECG (UHR ECG) – for early detection of myocardial ischemia (MIS). The utility of UHR ECG vs. conventional ECG (C ECG) was tested in anesthetized rats and pigs. Transmural MIS was induced in rats by the ligation of the left coronary artery (CA). In pigs, subendocardial ischemia of variable extent was produced by stepwise inflation of balloon within the right CA causing 25-100% reduction of its lumen. In rats, a reduction in power spectral density (PSD) in high-frequency (HF) channel of UHR ECG was registered at 60 s after ischemia (power 0.81±0.14 vs. 1.25±0.12 mW at baseline, p<0.01). This was not accompanied by any ST segment elevation on C ECG. In pigs, PSD in HF channel of UHR ECG was significantly decreased at 25% reduction of CA lumen, while ST segment on C ECG remained unchanged. In conclusion, UHR ECG enabled earlier detection of transmural MIS compared to C ECG. PSD in HF-channel of UHR ECG demonstrated greater sensitivity in the settings of subendocardial ischemia.

CNN-based off-the-shelf features have shown themselves as a good baseline for trademark retrieval. However, in recent years, the computer vision area was transitioning from CNNs to a new architecture – Vision Transformer. In this paper, we investigate the performance of off-the-shelf features extracted with vision transformers and explore the effects of pre, post-processing, and pre-training on big datasets. We propose a method of joint usage of global and local features, which leverages the best aspects of both approaches. Experimental results on METU Trademark Dataset show that off-the-shelf features extracted with ViT-based models outperform off-the-shelf features from CNN-based models. The proposed method achieves the mAP value of 31.23, surpassing previous state-of-the-art results. We assume that the proposed approach for the trademark similarity evaluation will allow one to improve the protection of such data with the help of artificial intelligence methods. Moreover, this approach will allow one to identify cases of unfair use of such data and form an evidence base for litigation.

It is well known that X-ray crystallography is based on X-ray diffraction (XRD) by atoms and molecules. The diffraction pattern arises as a result of scattering of incident radiation, which makes it possible to determine the structure of the scattering substance. With the advent of ultrashort radiation sources, the theory and interpretation of X-ray diffraction analysis remained the same. This work shows that when an attosecond laser pulse is scattered on a DNA molecule, including during its nicking and bending, the pulse duration is an important characteristic of the scattering. In this case, the diffraction pattern changes significantly compared to the previously known scattering theory. The results obtained must be used in XRD theory to study DNA structures, their mutations and damage, since the previously known theory can produce large errors and, therefore, the DNA structure can be “deciphered” incorrectly.

When presenting special relativity, it is customary to single out the so-called paradoxes. One of these paradoxes is the formal occurrence of speeds exceeding the speed of light. An essential part of such paradoxes arises from the incompleteness of the relativistic calculus of velocities. In special relativity, the additive group is used for velocities. However, the use of only group operations imposes artificial restrictions on possible computations. Naive expansion to vector space is usually done by using non-relativistic operations. We propose to consider arithmetic operations in the special theory of relativity in the framework of the Cayley–Klein model for projective spaces. We show that such paradoxes do not arise in the framework of the proposed relativistic extension of algebraic operations.

We investigated the magnetic properties of antiferromagnetic (AFM) topological insulator MnBi$_2$Te$_4$ with partial substitution of Mn atoms by non-magnetic elements (A$_x^{IV}$ = Ge, Pb, Sn). Samples with various element concentrations (10-80%) were studied using SQUID magnetometry. The results demonstrate that, for all substitutes the type of magnetic ordering remains AFM, while the Nèel temperature (T$_N$) and spin-flop transition field (H$_{SF}$) decrease with increasing A$_x^{IV}$ = Ge, Pb, Sn concentration. The rate of decrease varies among the elements, being highest for Pb, followed by Sn and Ge. This behavior is attributed to combined effects of magnetic dilution and lattice parameter increase on magnetic properties, most prominent in (Mn$_{1−x}$Pb$_x$)Bi$_2$Te$_4$. Besides this, the linear approximation of experimental data of T$_N$ and H$_{SF}$ suggests higher magnetic parameters for pure MnBi$_2$Te$_4$ than observed experimentally, indicating the possibility of their non-monotonic variation at low concentrations and the potential for enhancing magnetic properties through doping MnBi$_2$Te$_4$ with small amounts of nonmagnetic impurities. Notably, the (Mn$_{1−x}$Pb$_x$)Bi$_2$Te$_4$ sample with 10% Pb substitution indeed exhibits increased magnetic parameters, which is also validated by local analyses using ARPES. Our findings shed light on tailoring the magnetic behavior of MnBi$_2$Te$_4$-based materials, offering insights for potential applications in device technologies.

Uremic toxins are the compounds that emerge in the blood when kidney excretory function is impaired. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually death during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes rise during uremia; however, the exact origin for most of them is still discussable. There are 3 main sources for such compounds: exogenous ones are consumed with food, whereas endogenous are produced by host metabolism or by symbiotic microbiota metabolism. In this article, we identified uremic toxins presumably of gut microbiota origin. We analyzed various databases to get information on enzymatic reactions in bacteria and human organism potentially yielded uremic toxins and to determine what toxins could be synthetized in bacteria residing in human gut. We selected biochemical pathways resulting in uremic toxins synthesis related to specific bacterial strains, and revealed links between toxin concentration in uremia and the proportion of different bacteria species, which can synthesize it. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of a particular toxin synthesis by the human metabolism. Finally, we analyzed which bacteria are potentially producing the biggest number of uremic toxins as well as which bacteria are decomposing them. Our study presents a bioinformatics-based approach for both elucidation of the origin of uremic toxins and search of the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.

Experimental optimization of analytical methods based on solid-phase microextraction (SPME) is a complex and labor-intensive process associated with uncertainties. Using the theoretical basics of SPME and finite element analysis software for the optimization proved to be an efficient alternative. In this study, an improved finite element analysis-based model for SPME of volatile organic compounds (VOCs) by porous coatings was developed mainly focussing on the mass transport in coatings. Benzene and the Carboxen/polydimethylsiloxane (Car/PDMS) coating were used as the model VOC and a porous SPME coating, respectively. It has been established that in the coating, volumetric fractions of Carboxen, PDMS, and air are 33, 42 and 24%, respectively. Knudsen diffusion in micropores can slow down a mass transport of analytes in the coating. When PDMS was considered as the solid part of the coating, lower root-mean-square deviation of the modeling results from experimental data was observed. It has been shown that the developed model can be used to model the extraction of VOCs from air and water samples encountered in a typical SPME development method procedure. It was possible to determine system equilibration times and use them to optimize sample volume and Henry’s law constant. The developed model is relatively simple, fast, and can be recommended for optimization of extraction parameters for other analytes and SPME coatings. The diffusivity of analytes in a coating is an important property needed for improved characterization of existing and new SPME polymers and analytical method optimization.

The uterine leiomyoma is the most common benign tumor in women of childbearing age. It may lead to problem of conception or complications during gestational period. The methods of treatment can be surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (Ulipristal acetate, Leuprolide acetate, Cetrorelix, Goserelin, Mifeprestone). Both approaches are efficient, but are incompatible with pregnancy planning. Therefore, there is a call for medical practice in developing therapeutical means of preventing leiomyoma onset in patients planning on pregnant. Based on the analysis of GWAS data on the search for mononucleotide polymorphisms associated with the risk of leiomyoma, meta-transcriptomic and meta-methylomic studies, target proteins have been proposed. Prospective therapeuticals of leiomyoma may be based on chemical compounds, humanized recombinant antibodies, vaccines based on markers of the uterine leiomyoma cells that are absent in the adult organism, DNA and RNA preparations. Three different nosological forms of the disease associated with driver mutations in the MED12, HMGA2 and FH genes should be considered when developing or prescribing drugs. E.g. synthetic inhibitors and vaccines based on matrix metalloproteinases MMP11 and MMP16 are expected to be effective only for the prevention of the occurrence of MED12-dependent nodules.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Purpose of the study: to reveal how the transfusion and the refraining from it affects the neuro-vascular unit in the congenital heart defects correction with cardiopulmonary bypass. Materials and methods: in vitro research, we formed a model of a neurovascular unit, which contains neu-rons, astrocytes and endothelial cells. This cellular model was cultivated in hypoxia conditions with the oxygen saturation levels of 1, 2, 3, 4%. In addition, this unit was cultivated with the pa-tient's serum adding in two different groups - with minimal and maximal levels of system in-flammatory response that we estimated by IL-6 level. Results: We found that during incubation in hypoxic conditions, the level of transendothelial resistance changed in groups with oxygen levels of 1% and 2% only after 4 hours. When we cultivated neurovascular unit cells with patients' sera, we found a minimal level of transendothelial resistance at 4 hours that increased after 24 hours. Permeability analysis showed that its level significantly decreased in the 1% and 2% oxygen group at 60- and 90-minutes relative to the control group. Conclusion: the system inflammatory response has more expressed but less long effect on the neurovascular unit model than hypoxia.

A closed chain of oscillators can be considered as a model of ring-shaped ecosystems, such as atolls or coastal zones of inland reservoirs. As an oscillator model, we use the logistic map that often referred to as an archetypical example of how complex dynamics can arise from very simple nonlinear equations. We investigate the influence of the model parameters both on the nature of oscillations in the oscillator ring and on the spatial structures that arise in this case. Namely, we demonstrate a variety of emerging spatial structures depending on the initial conditions.

The redefined vacuum approach, which is frequently employed in the many-body perturbation theory, proved to be a powerful tool for formula derivation. Here, we elaborate this approach within the bound-state QED perturbation theory. In addition to general formulation, we consider the particular example of a single particle (electron or vacancy) excitation with respect to the redefined vacuum. Starting with simple one-electron QED diagrams, we deduce first- and second-order many-electron contributions: screened self-energy, screened vacuum polarization, one-photon exchange, and two-photon exchange. The redefined vacuum approach provides a straightforward and streamlined derivation and facilitates its application to any electronic configuration. Moreover, based on the gauge invariance of the one-electron diagrams, we can identify various gauge-invariant subsets within derived many-electron QED contributions.

Chromosomal rearrangements in N. gonorrhoeae and N. meningitidis were studied with the determination of mobile elements and their role in rearrangements. The results of whole-genome sequencing and de novo genome assembly for 50 N. gonorrhoeae isolates collected in Russia were compared with 96 genomes of N. gonorrhoeae and 138 genomes of N. meningitidis from the databases. Rearrangement events with the determination of the coordinates of syntenic blocks were analyzed using the SibeliaZ software, the minimum number of events that allow one genome to pass into another was calculated using the DCJ-indel model using the UniMoG program. Population-level analysis revealed a stronger correlation between changes in the gene order and phylogenetic proximity for N. meningitidis in contrast to N. gonorrhoeae. Mobile elements were identified, including Correa elements, Spencer-Smith elements (in N. gonorrhoeae), Neisserial intergenic mosaic elements, IS elements of IS5, IS30, IS110, IS1595 groups, Nf1-Nf3 prophages, NgoФ1-NgoФ9 prophages, Mu-like prophages Pnm1, Pnm2, MuMenB (in N. meningitidis). More than 44% of the observed rearrangements most likely occurred with the participation of mobile elements, including prophages. No differences were found between the Russian and global N. gonorrhoeae population both in terms of rearrangement events and in the number of transposable elements in genomes.

Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. Detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research of immunogenicity and duration of antibody response to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in hemagglutination inhibition assay. The dynamics of anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase, and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody level after vaccination directly correlated with titers before vaccination. Difference was found in response to NA antigen between split and subunit adjuvanted vaccines and in NA functional activity in the vaccine formulations.

To obtain a given structure in 3D building-up modes, it is necessary to use optimal surfacing modes that determine the amount of heat input in local areas. For this purpose, aluminum bronze was surfacing onto a deformed base and the structure and its characteristics in the surfacing and heat-affected zones were studied by the EBSD method. The heterogeneity of the formation of the structure in each selected zone is established, which indicates the heterogeneity of heat input in local areas of the material in one mode of surfacing. For typical cases of crystallization, a molecular dynamics simulation of crystallization processes with different heat input to the base with characteristics specified based on experimental data was carried out. It has been established that the amount of heat input determines the degree of melting and the inherited defectiveness of growing crystals. The formation of misorientation boundaries and crystallization centers of new grains is determined by the conditions of joint growth of grains with given crystallographic parameters of the computational model. Numerical calculations agree with the experimentally observed results.

The problem of optimal scheduling in a system with parallel queues and a single server has been extensively studied in the queueing theory. However, such systems have mostly been studied by assuming homogeneous attributes of arrival and service processes, or in heterogeneous case a Markov random process was usually assumed. In this paper, we explore the possibility of combining simulation and neural network paradigms for optimal scheduling in a heterogeneous system with an arbitrary inter-arrival and service time distributions. The service of any queue by the server is exhaustive. Further routing of the server after the queue has been emptied is as instructed by the trained neural network. Any change in the queue that currently has a server is accompanied by a switching cost. The simulated annealing optimization algorithm which is used to optimize the parameters of the neural network was adapted for numerically evaluated average cost function. A Markov decision problem was formulated for the corresponding markovian queueing system to verify the results of solving the optimization problem. In addition to comparing the actual values of the average cost, the parameter values of the neural network trained on the optimal control policy of the Markov model are also used to determine the domains of parameters required for the simulated annealing defined on a finite discrete domain. Numerical analysis shows the effectiveness of this approach. Moreover, a comparison of the results for different distributions illustrates the insensitivity of the optimal control policy to the shape of the distributions for the same two first moments. Thus, the optimal control policy for an exponential model can be used as a suboptimal one for the general system.

Curcumin attracts a huge attention because of its biological properties: antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the suspension method and were characterized by dynamic and electrophoretic light scattering, transmission electron microscopy and atomic force microscopy. The average particle size was 200 nm, and ζ-potential was -4 mV. Curcumin release studies showed that nanoparticles are stable in water solution. In vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to pure curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. Median lethal dose was determined in acute toxicity assay on Zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.

Porous ferroelectric lead zirconate-titanate (PZT) films are a promising material for various electronics applications. This study focuses on understanding how structure-directing agent (polyvinylpyrrolidone) can change structure and electrical properties of porous PZT films prepared by chemical solution deposition. The films with various porosity up to ~ 40 vol.% and pore connectivity changing from 3-0 to 3-3 were prepared and studied by capacitance-voltage, dielectric hysteresis, transient current, photocurrent, and local current techniques. We have found that the linear decrease in the material volume in a porous film is not the only factor governing film properties. The key role in changing electrical properties plays the creation of new internal grain boundaries. This research expands the understanding of physical phenomena in porous ferroelectric films and may enable the development of new materials and devices.

Phylostratigraphic analysis is a way to look anew on phylogenetic data in the evolutionary aspect. It allows counting the evolutionary age based on the analysis of genes, their orthologs and finding the last common ancestor. We performed phylostratigraphic analysis of Arabidopsis thaliana genes associated with several types of abiotic stresses (heat, cold, water-related, light, osmotic, salt, and oxidative) determined by the Gene Ontology annotation. Comparison of the distributions of ages of genes associated with stresses of different type has shown the heat stress to involve older genes while the light stress – younger genes. At the same time, all types of stress are characterized by a significantly higher proportion of old genes (common to all eukaryotes) compared to the whole set of A.thaliana genes. This can be explained by the involvement of basic molecular processes in plant cells into the stress response. Reconstruction and graphical analysis of the gene network of the heat stress educed several clusters associated with different response functions. Some of these clusters contain only ancient genes. The results obtained show that the phylostratigraphic analysis reveals the fundamental features of the organization of gene networks and their evolution.

Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24-48 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 μM) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation.

The antioxidant potential (capacity and activity) of aqueous fullerene dispersions (AFD) of non-functionalized C₆₀, C₇₀, and Gd@C₈₂ endofullerene (in micromolar concentration range) was estimated based on chemiluminescence measurements of the model of luminol and generation of organic radicals by 2,2’-azobis(2-amidinopropane) dihydrochloride (ABAP). The antioxidant capacity was estimated by the TRAP method, from the concentration of half-suppression, and from the suppression area in the initial period. All three approaches agree and show that the antioxidant capacity of AFDs increased in the row Gd@C₈₂ < C₇₀ < C₆₀. Mathematical modeling of the long-term kinetics data was used for antioxidant activity estimation. The effect of C₆₀ and C₇₀ is found to be quenching of the excited product of luminol with ABAP-generated radical and not an actual antioxidant effect; quenching constants differ insignificantly. Apart from quenching with a similar constant, the AFD of Gd@C₈₂ exhibits actual antioxidant action. The antioxidant activity in Gd@C₈₂ is 300-fold higher than quenching constants.

We have recently reported that a series of 1,3,4-oxadiazol-2-ylbenzenesulfonamides acts as potent and specific monoamine oxidase B (MAO-B) inhibitors with some compounds possessing potencies in the nanomolar range. While sulfonamide compounds (e.g., zonisamide) have been reported to inhibit the MAO enzymes, nanomolar MAO inhibition potencies for this class are not frequently observed. The present study expanded on these findings by replacing the 1,3,4-oxazole moiety with a 1,3-thiazole heterocycle. A series of 23 primary sulfonamides were synthesized by reaction of an α-haloketone with a substituted carbothioamide. The results of the MAO inhibition studies showed that the 1,3-thiazolylbenzenesulfonamides were specific inhibitors of human MAO-B. The most potent MAO-B inhibitor exhibited an in vitro IC50 value of 0.103 µM (3j). The derivatives were, however, weaker inhibitors of human MAO-A with the most potent compound exhibiting an IC50 value of 11.9 µM (3a). Examination of the structure-activity relationships (SARs) showed that the most potent MAO-B inhibition was obtained with substitution of the sulfonamide on the meta position of the phenyl rather than the para position. This study concludes that 1,3-thiazolylbenzenesulfonamides represent a class of potent and specific MAO-B inhibitors, which may serve as leads for the development of new treatments for disease states such as Parkinson’s disease.

The effects of methyl jasmonate (MeJ) on growth and taxoid formation in the cell culture of Himalayan yew was investigated for elucidate the specifics of the action of phytohormones on dedifferentiated plant cells in vitro. The characteristics of the same suspension culture of Taxus wallichiana was compared in 2017 ("young culture") and in 2022 ("old culture") - 1.5 or 6 years after culture induction, respectively. Cells were grown in flasks and bioreactors, MeJ (100 µM) was added at the exponential growth phase. It was found that cell culture demonstrated good growth (dry weight (DW) accumulation 10–18 g/l, specific growth rate µ = 0.15–0.35 day-1) regardless of "age", cultivation system and MeJ addition. UPLC–ESI-MS analysis showed the presence of C14-hydroxylated taxoids (yunnanxane, taxuyunnanine C, sinenxane C, sinenxane B) in cell biomass in the amounts comparable to plants. The content of C14-OH taxoids during 5 years of cultivation increased by 3-5 times. It was 0.2–1.6 mg/g DW for "young culture” and 0.6-10.1 mg/g for “old culture” depending on cultivation conditions. The ratio of individual compounds changed also: in the "young culture" was predominant yunnanxane, in the "old culture" - sinenxane C. Important that C13-hydroxylated taxoids were found in trace amounts only in the "young culture” (below 0.05 mg/g DW) and were not detected in the "old culture”. The response to MeJ was radically different depending on culture’s «age». In the “young culture”, exogenous MeJ had no effect on the content of C14-OH com-pounds, but significantly (almost 10 times) increased the content of C13-OH compounds. In particular, paclitaxel concentration was elevated up to 0.12–0.19 mg/g DW, which is comparable to its content in the bark of yew trees. By contrast, MeJ added to the "old culture” had minor effect on the synthesis of C13-OH toxoids that appeared in trace amounts only (below 3.5 µg/g DW for paclitaxel) but notably increased the content of C14-OH compounds (1.5–2.0 times in flasks and 5–8 times in bioreactors). These findings suggest that hormonal signaling in dedifferentiated yew cells grown in vitro is different from that in plants and change with culture age. This might be a result of the high level of heterogeneity of cells in vitro and their constant auto-selection for proliferate intensity which leads to predominant formation of C14-OH taxoids versus C13-OH taxoids and modified cell response to exogenous MeJ treatment. These results have both fundamental and practical biotechnological application.

Glutamate excitotoxicity is implicated in the pathogenesis of many disorders, including stroke, traumatic brain injury, and Alzheimer’s disease, for which central insulin resistance is a comorbid condition. Massive glutamate release primarily through ionotropic N-methyl-D-aspartate receptors (NMDARs) causes a sustained rise in [Ca2+]i, followed by mitochondrial depolarization and an increase in intracellular O2• (superoxide) production. Recently, we found that insulin protected neurons against excitotoxicity by diminishing the delayed calcium deregulation (DCD), However, a role of insulin in superoxide production in excitotoxicity still needs to be clarified. The present study is aimed to investigate the effects of insulin on glutamate-evoked superoxide generation and DCD using the fluorescent indicators dihydroethidium, MitoSOX Red, and Fura-FF in rats cultured cortical neurons. We found that insulin significantly diminished both the intracellular and mitochondrial superoxide production in neurons exposed to glutamate and there was a strong linear correlation between [Ca2+]i and intracellular superoxide. MK 801, an inhibitor of NMDAR-gated Ca2+ influx, completely abrogated the glutamate effects in both the presence and absence of insulin. In experiments on sister cultures, insulin diminishes neuronal death. Thus, collectively, data obtained suggest that insulin diminishes glutamate-induced superoxide production in neurons via fall of [Ca2+]i increased and thereby improves viability of neurons

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a-f) with a protonated endocyclic nitrogen atom and then heterocyclic salts (3a-j) containing a 4-imidazoline ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a-j towards hydrolysis and alcoholysis makes them excellent candidates for the search of new types of biologically active compounds.

X-ray diffraction (XRD) analysis of complex poly-atomic systems, especially of biomolecules, using ultra-short laser pulses (USP), is currently one of the most important fields of modern physics. The basis for interpreting and "deciphering" experimental data is the well-known theory of X-ray scattering, where the main parameter of USPs - its duration - is not taken into account. In the present work it is shown that for scattering of attosecond USPs on DNA and RNA trinucleotides the pulse length is the most important scattering parameter. In this case the diffraction pattern significantly changes with respect to the previously known scattering theory. The results obtained are extremely important in XRD when using attosecond pulses to study trinucleotides of DNA and RNA because using the previously known scattering theory which does not take into account the duration of USPs one can not correctly interpret and therefore "decode" DNA and RNA structures.

Two series of novel [1,2,4]triazolo[4,3-c]- and [1,2,4]triazolo[1,5-c]quinazoline fluorophores with 4’-amino[1,1′]-biphenyl residue at position 5 have been prepared via Pd-catalyzed cross-coupling Suzuki-Miyaura reactions. The treatment of 2-(4-bromophenyl)-4-hydrazinoquinazoline with orthoesters in solvent-free conditions or in absolute ethanol leads to the formation of [4,3-c]-annulated triazoloquinazolines, whereas [1,5-c] isomers are formed in acidic media as a result of Dimroth rearrangement. 1D-NMR and 2D-NMR spectroscopy as well as single‐crystal X‐ray diffraction analysis unambiguously confirmed the annelation type and determined the molecular structure of p-bromophenyl intermediates and target products. Photophysical properties of the target compounds were investigated in two solvents and solid state and compared with those of related 3-aryl-substituted [1,2,4]triazolo[4,3-c]quinazolines. The excluding of aryl fragment from triazole ring has been revealed to improve fluorescence quantum yield in solution. Most of the synthesized structures show moderate to high quantum yields in solution. Additionally, the effect of solvent polarity on the absorption and emission spectra of fluorophores has been studied and considerable fluorosolvatochromism was stated. Moreover, electrochemical investigation and DFT calculations have been performed, their results are consistent with the experimental observation.

Modification the biodegradable matrix was carried by graft-copolymerization polylactide with methacrylic acid of various concentrations. Ultraviolet irradiation with different exposure times to the samples was chosen as the initiator of copolymerization. In the experiment the effect of ultraviolet light on polylactide and graft copolymerization was investigated: the resulting samples were studied by viscosimetry, gravimetry, FTIR, static cation- exchange capacity analysis . The conditions for obtaining grafted copolymers and the dependence of the characteristics on the reaction conditions are established.

Vegetation indexes help perform precision farming because they provide useful information regarding moisture, nutrient content, and crop health. Primary sources of those indexes are satellites and unmanned aerial vehicles equipped with expensive multispectral sensors. Reducing the price of obtaining such information would increase the availability of precision farming for small farms. Several studies have proposed deep neural network methods to estimate the indexes from RGB color images. However, these methods report relatively large errors for mature plants when highly non-linear relationships of images and vegetation indexes arise. One could apply multilayer random forest-based models (Deep Forests) to solve this problem, but the discriminative power of such models is limited: they cannot catch complex dependencies between image features. In this paper, we propose a method that combines ideas of deep forests, random forests of kernel trees, and global pruning of random forests to tackle the problem. As a result, the method considers the properties of objects with a complex structure: the presence of relationships between groups of features, displacement, and scaling of objects. The experimental results show that the proposed method outperforms neural network-based solutions in several datasets.

The synthesis of additives for thinning mineral suspensions based on sodium polyacrylate was carried out. The effect of molecular weight regulators on the molecular weight characteristics of the polymer and the effect of such polymers on the rheological properties of suspensions was studied. Sodium acrylate polymers are synthesized by free radical polymerization in aqueous solution using molecular weight regulators. The molecular weight characteristics of the polymeric samples were estimated by viscometry using Mark-Houwink-Kuhn-Sakurada (MHKS) equation. Synthesized polymers were used as thinners ceramic slurries, prepared according to the recipe of the enterprises producing ceramic products. The thinning ability of polymer samples with different molecular weights was estimated using an Engler viscometer from the time of the ceramic slurry flow. The influence of the type and amount molecular weight regulator on polyacryates was revealed. It was found that molecular weight synthesized samples was in the range of 21000 - 91000. It was determined that samples with a molecular weight of 28000 - 35000 synthesized using mercaptoethanol (at a dosage of 0.5-1.5% by weight of the monomer) provide optimal fluidity to the ceramic slurry.

Abstract: CRISPR/Cas systems are used for genome editing, both in basic science and in bio-technology. At the same time, CRISPR/Cas editors have several limitations, including insufficient specificity leading to "off-targets" and the dependence of activity on chromatin state. A number of highly specific Cas9 variants have been obtained now, but most of them are characterized by reduced activity on eukaryotic chromatin. We identified a spatial cluster of amino acid residues in the PAM-recognizing domain of Streptococcus pyogenes Cas9, whose mutations restore the activity of one of the highly specific forms of SpyCas9 without reducing its activity in Saccharomyces cere-visiae. In addition, one of these new mutations also increases the efficiency of SpyCas9-mediated editing of a site localized on the stable nucleosome. The improved Cas9 variants we obtained, which are capable of editing hard-to-reach regions of the yeast genome, may help in both basic research and yeast biotechnological applications.

In recent years, different deep learning frameworks were introduced for hyperspectral image (HSI) classification. However, the proposed network models have a higher model complexity and do not provide high classification accuracy if few-shot learning is used. This paper pre-sents an HSI classification method that combines random patches network (RPNet) and re-cursive filtering (RF) to obtain informative deep features. The proposed method first convolves image bands with random patches to extract multi-level deep RPNet features. Thereafter, the RPNet feature set is subjected to dimension reduction through principal component analysis (PCA) and the extracted components are filtered using the RF procedure. Finally, HSI spectral features and the obtained RPNet-RF features are combined to classify the HSI using a support vector machine (SVM) classifier. In order to test the performance of the proposed RPNet-RF method, some experiments were performed on three widely known datasets using a few training samples for each class and classification results were compared with those obtained by other advanced HSI classification methods adopted for small training samples. The comparison showed that the RPNet-RF classification is characterized by higher values of such evaluation metrics as overall accuracy and Kappa coefficient (https://github.com/UchaevD/RPNet-RF).

Current understanding of mechanisms of cellular resistance to genotoxic stress is incomplete but is critical for a variety of medical applications. Recent developments in the CRISPR/Cas technologies open new opportunities for targeted interrogation of resistance genes and pathways. In the present work, we used nuclease dead Cas9 constructs to achieve targeted overexpression of endogenous genes encoding two essential subunits of DNA damage sensor complex, XPC and HR23B, in HEK293T cells. Both individual and simultaneous overexpression of the two genes was achieved and the effects on cellular resistance to ionizing radiation and paraquat was examined. Using the fluorometric microculture cytotoxicity assay, we showed that simultaneous, but not separate overexpression of the two genes lead to a 30% increase in survivability. Irradiated cells that overexpressed both XPC and HR23B genes showed higher clonogenic capacity and proliferation rate compared to the irradiated transfection control as revealed by the clonogenic survival assay. Modulation of the gene expression did not affect cell resistance to paraquat. In summary, our results demonstrate a high potential of CRISPR/dCas9-enabled multiplex overexpression of stress-response genes in functionally justified combinations, exemplified here by the XPC-HR23B complex, for achieving an enhanced cellular radioresistance.

The basis of modern teeth whitening systems is the use of a whitening gel, usually containing hydrogen peroxide or carbamide peroxide. The purpose of our study was to evaluate the effect of chemical and modified office teeth whitening systems on the mineral metabolism of oral fluid and to determine a safer method. The study covered 81 patients aged 22 to 35 years of both sexes with teeth color A2 and darker on the Vita Classic scale. Determination of the concentration of calcium and phosphates in the oral fluid was carried out on a spectrophotometer using ready-made Human kits. Chemical tooth whitening was performed using a gel based on 40% hydrogen peroxide. After the procedure, remineralization therapy with enamel-sealing liquid was performed for 14 days. The obtained results indicate that the most pronounced changes in the content of calcium (+74.4%, p &lt;0.001) and рhosphates (phosphorus) (-23.07%, p &lt;0.001) were observed when using a chemical bleaching system. After the teeth whitening procedure using a modified technique, less pronounced changes in the concentrations of calcium (+29.07, p &lt;0.001) and phosphorus (-14%, p &lt;0.001) were observed. The use of remineralizing agents led to a faster recovery of the initial levels of calcium and phosphates in the oral fluid. Both bleaching systems caused similar changes in the chemical composition of the oral fluid.

Hafnium is a metal with rare properties, such as a low superconducting transition temperature slightly above 100 mK, which makes it attractive for a lot of applications, especially for design and fabrication of microcalorimeters with high energy resolution. In this paper we describe the results of fabrication and experimental investigation of superconducting properties of hafnium thin films in a dilution refrigerator. The considered Hf films, whose thickness is in the range from 60 to 115 nm, are deposited on substrates by electron beam evaporation. The combinations with thin layers of normal metals to decrease the critical temperature of superconducting hafnium films by proximity effect, are also considered. The critical temperature of the studied films varies from 56 to 302 mK. Also, significant increase of the critical temperature of some films over time was observed and investigated.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

Herein, we demonstrate the synthesis of sandwiched composite nanomagnets, which consist of hard magnetic Cr-substituted hexaferrite cores and magnetite outer layers. The hexaferrite plate-like nanoparticles with average dimensions of 36.3 nm × 5.2 nm were prepared by glass crystallization method and were covered by spinel-type iron oxide via thermal decomposition of iron acetylacetonate in hexadecane solution. The hexaferrite nanoplates act as seeds for the epitaxial growth of the magnetite, which results in uniform continuous outer layers on both sides. The thickness of the layers can be adjusted by controlling the concentration of metal ions. In this way, layers with average thickness of 3.7 and 4.9 nm were obtained. Due to an atomically smooth interface the magnetic composites demonstrate the exchange coupling effect, acting as single phases during remagnetization. The developed approach can be applied to any spinel-type material with matching lattice parameters and opens the way to expand the performance of hexaferrite nanomagnets due to a combination of various functional properties.

Climate warming is expected to have pronounced effects on Arctic and Subarctic ecosystems, especially regions underlain by discontinuous and relatively warm permafrost. The main goal of this research is to evaluate the vulnerability and dynamics of permafrost under climate warming across the various ecotypes in respect of ecosystem stability, socioeconomic impact, and for better understanding possible future environmental changes. We suggested the new version of the spatially distributed permafrost dynamics model (GIPL2-MPI), which is developed in the Geophysical Institute, University of Alaska Fairbanks. This model is based on the ecosystem approach to simulate the permafrost dynamics, which we are discussing in this paper. We combined ground-based observations and numerical freeze/thaw modeling using climate-ecosystem-permafrost interactions to understand the physical processes and mechanisms controlling permafrost physical state. We predict the changes in permafrost conditions using output from two GCMs (NCAR-CCSM4 and GFDL-CM3) and Five-Model Average Ensemble for the RCP-4.5 and RCP-8.5 scaled down to 1 by 1 km spatial resolution (https://uaf-snap.org/) across entire Alaska. Our result shows that by the end of the current century widespread near-surface permafrost degradation could begin everywhere in Alaska southward of the Brooks Range as well as across some spots at the North Slope Alaska.

Ferroptosis is a unique variety of non-apoptotic cell death, driven by massive lipid oxidation in an iron-dependent manner. Since Ferroptosis was introduced as a concept in 2012, it was shown it's essential role in the pathogenesis in neurodegenerative diseases and an important role in therapy-resistant cancer cells. Thus, a detailed molecular understanding of both canonical and alternative ferroptosis pathways are required. There is a set of widely used chemical agents to modulate ferroptosis using different pathway targets: Erastin blocks cystine-glutamate antiporter, system xc-; ML210 directly inactivate GPX4; L-buthionine sulfoximine (BSO) inhibits γ-glutamylcysteine synthetase, an essential enzyme for glutathione synthesis de novo. Most studies were focused on lipidomic profiling of model systems undergoing death in a ferroptotic modality.

The accommodative response of the human eye is predominantly driven by foveal vision but reacts also to off-foveal stimuli. Here, we report on monocular accommodation measurements using parafoveal and perifoveal annular stimuli centered around the fovea and extending up to 8 degree radial eccentricity for young emmetropic and myopic subjects. The stimuli were presented through a sequence of random defocus step changes induced by a pupil-conjugated tunable lens. A Hartmann-Shack wavefront sensor with an infrared beacon was used to measure real-time changes of ocular aberrations up to and including the 4th radial order across a 3 mm pupil at 20 Hz. Our findings show a significant reduction in accommodative response with increased radial eccentricity.

Abstract: The establishment of a circular economy in the mining sector, taking advantage of innovations in the exploration and development of hydrocarbon reserves, [ ], their [ ], transportation [ ] and subsequent processing [ ] are significant concerns. The issues surrounding the employment of technology targeted at enhancing environmental safety to increase the productivity of the reproduction process of the natural gas and oil resource base are equally important. The paper discusses the use of green seismic technology of survey to determine the oil and gas potential of the subsoil. A methodological toolkit is proposed for carrying out technical and economic calculations to determine indicators of the environmental and economic efficiency of using innovative resource-saving technology for geological survey in areas densely planted with forests. The purpose of the work is to establish the viability of employing resource-saving technology known as Green Seismic to search for promising hydrocarbon objects in forested areas and determine the expected environmental and economic benefits of geological exploration using the suggested enhanced methodology for their evaluation. The tasks set to achieve the goal were solved using methods of geological and economic assessment of the hydrocarbon raw material potential of territories and water areas, environmental assessment of the negative influence of anthropogenic environmental impact on the natural environment, economic and statistical methods of performing technical and economic calculations to determine performance indicators for the implementation of innovative projects in the field of geological exploration. The novelty of the results obtained lies in the proposed improved algorithm for conducting an environmental and economic assessment of geological exploration for hydrocarbon raw materials, a conceptual description of the Green Seismic technology, systematization of technical, economic, and environmental risks, justification of new regional directions for geological exploration using resource-saving seismic exploration technology.

Emerald ash borer (EAB), Agrilus planipennis, is an invasive beetle of East Asian origin that in North America and Russia killed millions of ash trees (Fraxinus spp.). In September 2020, EAB was de-tected in Saint Petersburg, becoming resonant event for the metropolitan city. The aim of the present study was to investigate occurrence and ecology of EAB in Saint Petersburg. The presence of two distinct enclave populations of EAB was revealed, each of which has (very likely) been established by separate events of “hitchhiking” transport vehicles. Following the invasion, further spread of EAB in Saint Petersburg was slow and locally restricted, main explanation for which is climatic factor. Due to spread by “hitchhiking”, the possibility of EAB further long-distance ge-ographic spread of EAB in the Baltic Sea region (EU) is high, and not only by ground transport (120–130 km distance from EU borders), but also by ferries transporting cars (traditional means of transportation across the Baltic Sea). In certain cases, development of EAB on F. excelsior was more successful (stem portion colonized, larval densities, number of galleries, exit holes, viable larvae, emerged beetles) than in (adjacent) F. pennsylvanica trees. Observed relatively high EAB-sensitivity of F. excelsior therefore questions the efficacy and benefits of the currently ongoing selection and breeding projects against ash dieback (ADB), caused by Hymenoscyphus fraxineus. Inventory, mapping, and monitoring of surviving F. excelsior trees in areas infested by both ADB and EAB are necessary to acquire genetic resource for work on strategic long-term restoration of F. excelsior, tackling (inevitable) invasion of EAB to the EU.

The outcomes of the present scientometric analysis of research in catalysis provide chemistry and catalysis scholars with a closer bibliometric knowledge of an old and central field of chemical research which is being reshaped by fundamental and technological advances spanning from single-atom heterogeneous catalysis to flow chemistry. Improving and widening research and education in catalysis is a strategic need for national economies. Four research policy guidelines aimed at fostering progress in catalysis research and education conclude the study.

Soil and Water Assessment Tool (SWAT) was used to simulate five glacierized river basins that are global in coverage and vary in climate. The river basins included the Narayani (Nepal), Vakhsh (Central Asia), Rhone (Switzerland), Mendoza (Central Andes, Argentina), and Central Dry Andes (Chile) with a total area of 85,000 km2. A modified SWAT snow algorithm was applied in order to consider spatial variation of associated snow melt /accumulation by elevation band across each subbasin. In the previous studies, melt rates varied as a function of elevation resulting from an air temperature gradient while the snow parameters were constant throughout the entire basin. A major improvement of the new snow algorithm is separating the glaciers from seasonal snow based on their characteristics. Two SWAT snow algorithms were evaluated in simulation of monthly runoff from glaciered watershed: 1) the snow parameters are lumped (i.e. constant throughout the entire basin) and 2) the snow parameters are spatially variable based on elevation band-subbasin (i.e. modified snow algorithm). Applying the distributed SWAT snow algorithm improved the model performance in simulation of monthly runoff with snow-glacial regime, so that mean RSR decreased to 0.49 from 0.55 and NSE increased to 0.75 from 0.69. Improvement of model performance was negligible in simulation of monthly runoff from the basins with monsoon runoff regime.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Triphenylphosphonium (TPP) derivatives of a decapeptide related to sequences of bactenecin 7 (Bac7) and oncocin (Onc112) were synthesized and studied as potential antimicrobial compounds using various biochemical and microbiological assays. It was shown that while the reduction of the Bac7 length to 10 a.a. residues dramatically decreases the affinity to bacterial ribosomes, the modification of peptide with alkyl-TPP moieties leads to an increase in the affinity. New analogs which structure combines a decapeptide related to Bac7 and Onc112 — Bac(1-10, R/Y) — and TPP, attached to the C-terminal amino acid residue through alkylamide linkers, inhibit translation in vitro and are found to be more selective inhibitors of bacterial translation as compared with eukaryotic translation, than Onc112 and Bac7. Triphenylphosphonium analogs of a decapeptide related to Bac7 and Onc112 suppress the growth of both gram-negative bacteria, similar to Onc112 and Bac7, and gram-positive ones as alkyl-TPP derivatives, and also act against some resistant laboratory strains. Bac(1-10, R/Y)-C2-TPP, containing a short alkylamide linker between the decapeptide and TPP, is transferred into the E. coli cells via the SbmA transporter protein. TPP derivatives of the decapeptide Bac(1-10, R/Y) containing either decylamide or ethylamide linker cause B. subtilis membrane depolarization, similar to alkyl-TPP. The Bac(1-10, R/Y)-C2-TPP analog is proved to be non-toxic for mammalian cells by MTT-test.

Shot peening has become a well-established technique for the introduction of beneficial compressive Residual Stresses (RS) into the near-surface layers of metallic materials for the purpose of preventing or suppressing fatigue crack nucleation and growth. Ti-alloys are widely used to fabricate compressor blades of aeroengines. Titanium blades that may be susceptible to different modes of damage under cyclic loading (high cycle fatigue, fretting fatigue) are often subjected to shot peening to extend their safe operating time. The control and monitoring of residual stresses in titanium blades is of great importance to assure the safety of aeroengines. The techniques for residual stress evaluation include mechanical methods (material removal) as well as physical methods such as X-ray diffraction. Perhaps the most common and practically accessible form of the latter is the method. Conventional laboratory X-ray diffractometers typically probe samples to the depths up to ~20 µm that correspond to 1x...5x the average grain size for typical metals and alloys. The limitations of the method have been identified and reviewed in the literature, motivating the use of other semi-destructive approaches to evaluate the residual stresses in deeper layers and at more sharply defined locations. In the present report we present a case study of the comparison between non-destructive and semi-destructive evaluation techniques, namely the X-ray diffraction method against the mechanical and FIB-DIC ring-core drilling applied to the samples of VT6 (Russian designation of Ti-6Al-4V) titanium alloy after shot peening with 1 mm steel balls. Mechanical drilling of circular holes of ~2 mm diameter with laser speckle interferometry monitoring of strains gives a rough spatial resolution of a few millimeters, while the Korsunsky FIB-DIC method of Ga-ion beam micro-ring core milling within FIB-SEM with Digital Image Correlation (DIC) deformation analysis delivers spatial resolution down to a few micrometers. Good agreement has been found between the X-ray and FIB-DIC estimates of RS variation profiles as a function of depth in shot peened titanium alloy samples. Some advances in the FIB-DIC method are presented and discussed in terms of the acceleration of data acquisition and interpretation.

UV induced photoluminescence of organosilica films with ethylene and benzene bridging groups in their matrix and terminal methyl groups on the pore wall surface is studied to reveal optically active defects and understand their origin and nature. Careful selection of the film’s precursors and conditions of deposition and curing, analysis of chemical and structural properties led to the conclusion that luminescence sources are not associated with the presence of oxygen-deficient centers, as in the case in pure SiO2. It is shown that the sources of luminescence are the carbon-containing components that are part of the low-k-matrix, as well as the carbon residues formed upon removal of the template and UV induced destruction of organosilica samples. A good correlation between the energy of the photoluminescence peaks and the chemical composition is observed. This correlation is confirmed by the results obtained by the Density Functional theory. The photoluminescence intensity increases with porosity and internal surface area. The spectra become more complicated after annealing at 400 °C, although Fourier transform infrared spectroscopy does not show these changes. The appearance of additional bands is associated with compaction of low-k matrix and segregation of template residues on the surface of the pore wall.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

In the current work, in continuation of our recent research [1] we synthesized and studied new chimeric compounds comprising the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP) connected by alkyl linkers of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly decrease membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP on bacterial ribosomes differ from that of CHL. By simulating the dynamics of complexes of CAM-Cn-TPP with bacterial ribosomes, we have proposed a possible explanation for the specificity of the action of these analogs on the translation process. CAM-C10-TPP and CAM-C14-TPP stronger inhibit the growth of the Gram-positive bacteria in comparison to the CHL and suppress some strains of CHL-resistant bacteria. Thus, we have shown that TPP derivatives of CHL are dual-acting compounds that target the ribosomes and the cellular membranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds contributes to the inhibitory effect on bacteria. Moreover, since the mitochondria of eukaryotic cells have qualities similar to those of their prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cells with these compounds.

Bioinformatics analysis of the sequences of orthologous zinc-containing peptidases of the M15_C subfamily revealed the presence of a conserved tryptophan residue near the active site, which is not involved in the formation of the protein core. Site-directed mutagenesis of this Trp114/109 residue using two representatives of the family, L-alanoyl-D-glutamate peptidases of bacteriophages T5 (Calcium-activated EndoT5) and RB49 (EndoRB49, without ion regulation) as an example, and further analysis of the 1H NMR spectra of the mutants showed that a decrease in the volume of the W → F → A residue leads to changes in the hydrophobic core and active center of the protein, and also decreased affinity for regulatory Ca2+ in the EndoT5 mutants. The inactive T5W114A mutant lacks the ability to bind the substrate. In general, the conserved Trp114/109 residue, due to the spatial restrictions of its side chain, significantly affects the formation of the catalytically active form of the enzyme and is critical for catalysis.

A power factor correction (PFC) rectifier is compulsory for any electronic circuitry connected to the electrical grid. The majority of PFCs that are utilized are based on a step-up converter that supplies high DC voltage at its output terminal. Electric vehicle battery voltage varies from a few hundred to almost a thousand volts. Thus, an additional conversion step is obligatory when designing an all-brand universal charger. This paper presents a new type of front-end versatile step up / down three voltage level PFC. The rectifier can operate in continuous conduction mode or discontinuous conduction mode. First, the rectifier’s principle of operation is described, and then an innovative rectifier is analyzed for continuous and discontinuous conduction modes. Finally, the proposed theory is experimentally validated in a multiplier-less dual loop mode at discontinuous conduction modes. It was shown that although there is no multiplier use in the control circuitry, the power factor is near unity. It was revealed that the rectifier could swing the output voltage from 50 V to 900 V while the input voltage was 230 Vrms. The innovative topology suits any standard PFC rectifier, three-level voltage supplement, and dual-stage low-voltage power supply.

Trio-based exome sequencing and high-resolution HLA typing were employed to analyze three patients with autoimmune adrenal insufficiency (AAI), including those with autoimmune polyglandular syndrome (APS) type 2, as well as their parents. Benign or likely benign variants of the AIRE gene were identified in all participants of the study. These variants, coupled with clinical data and the results of antibody studies to type I interferons, helped to exclude APS-1. Patients with APS-2, in contrast to patient with AAI, inherited distinct variants of unknown significance in the CLEC16A gene, which is associated with autoimmune diseases including AAI. Various risk alleles in other genes associated with autoimmunity were identified in all patients. HLA typing of second class loci revealed alleles related to APS types 2, 3, and 4. Nevertheless, the frequencies of the haplotypes identified are substantial in the healthy Russian population, precluding from regarding these alleles as genetic determinants linked to APS development. Immunological examination can detect antibody carriers and predict the risk of autoimmune disease development. In the future, to identify genetic predictors of autoimmune endocrinopathies, it is recommended to analyze the whole genome of patients and their relatives, examining clinically relevant variants in non-coding regions.

A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

Sulfite and kraft pulping are two principal methods of industrial delignification of wood. In recent decades, those have been considered as possibilities to pretreat recalcitrant wood lignocellulosics for enzymatic hydrolysis of polysaccharides and subsequent fermentation of obtained sugars to valuable bioproducts. Current work compares chemistry and technological features of two different cooking processes in the preparation of polysaccharide substrates for deep sacchari-fication with P. verruculosum glycosyl hydrolases. Bleached kraft and sulfite pulps were subjected to hydrolysis with enzyme mixture of high xylanase, cellobiohydrolase and β-glucosidase activities at a dosage of 10 FPU/g of dry pulp and fiber concentration of 2.5, 5 and 10%. HPLC was used to analyze soluble sugars after hydrolysis and additional acid inversion of oligomers to monosaccharides. Kraft pulp demonstrated higher pulp conversion after 48 h (74-99%), mostly resulted from deep xylan hydrolysis. Sulfite-pulp hydrolysates, obtained in similar conditions, due to higher hexose concentration (more than 50 g/L), had higher fermentability for industrial strains producing alcohols, microbial protein or organic acids. Along with saccharification, enzymatic modification of non-hydrolysed residues occurred, which led to decreased degree of polymerization and composition changes in two industrial pulps. As a result, crystallinity of kraft pulp increased by 1.3%, which opens possibilities for obtaining new types of cellulosic products in pulp and paper industry. The high adaptability and controllability of enzymatic and fermentation processes creates prospects for the modernization of existing factories.

We present a very computationally light and fast approximation algorithm and then verify it with genetic algorithm and simulated annealing. We show that our algorithm is on par with GA and SA in terms of output produced while having a tightly bounded time complexity. Our algorithm works best when there is a strong positive correlation between the reliability of a component and its cost. We present two algorithms with the same essence. One of them is system cost bounded and the other is target reliability bounded. Our proposed algorithm works on a subsystem level redundancy instead of component level redundancy.

Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people around the world. Neuronal death in AD is initiated by the toxic action of oligomeric amyloid-β (Aβ) peptides. The formation of membrane channels by Aβ is a primary molecular action and does not require any other proteins. Channels are formed by short amyloid fragments faster and more frequently than by full-length peptides. The channel formation is dependent on an electrostatic interaction between a positively charged peptide and a negatively charged membrane. Negative membranes can be found in several locations of a cell – the inner leaflet of plasma membrane, mitochondria, and lysosomes, which all are well-known cellular targets in AD. Considering that the amyloid enters a cell by endocytosis and is exposed to lysosomal enzymes, we propose the amyloid degradation toxicity hypothesis. Endopeptidases degrade the endocytosed peptide. Produced fragments form membrane channels, which can transfer various ions (including protons) and even relatively large compounds. The neutralization of lysosomal content inactivates enzymes, which fails the whole system of recycling cellular content, including autophagy. The permeabilization of lysosomes could also lead to cell death through necrotic and apoptotic mechanisms. We discuss several mechanisms that describe how amyloid degradation products reach plasma and mitochondrial membranes, and form membrane channels. The pathogenesis of AD is discussed at various levels in a context of how the primary molecular mechanism of membrane channel formation could progress into the disease state. The discussion starts at the molecular level and extends to why the development of a disease takes years and is closely associated with aging. The proposed hypothesis offers an interpretation to several clinical observations such as the involvement of iron metabolism and an inverse association between developing Alzheimer's disease and cancer. Predictions about potential biomarkers and effectiveness of future treatments are discussed.

Background: Evidence suggests that there is substantial comorbidity between fibromyalgia and Axis II pathology (i.e., personality disorders - PDs). The aim of the current study was to find out the exact cluster (A, B, C) PDs or traits that are more prominent in FM and may be predictors of FM diagnosis. Methods: Data from 86 subjects (53 with FM and 33 controls without FM) was analyzed in an observational, cross-sectional, comparative study. The assessment of categorical PDs and traits was performed independently with the Structured Clinical Interview for Personality Disorders (SCID-II). Binary logistic regression was used to determine FM predictors among PDs traits. Results. Compared with controls, FM patients had higher rate of PDs diagnoses (56.7 vs 18.2%, P&lt;.001). However, the rate was significantly higher only for borderline PD diagnosis (28.3% vs 6.1% P&lt;.05). The binary logistic regression analysis showed that schizotypal and schizoid (cluster A), borderline (cluster B), and dependent (cluster C) personality traits may be significant predictors of fibromyalgia (Nagelkerke R2 = 0.415). Conclusions: Our results may reflect association of FM with personality traits of all three PD clusters: A (eccentric), B (dramatic), C (anxious). However, the most consistent evidence seems to be for borderline PD.

The paper describes the research findings on dynamic and mechanical properties of composite elastomers with high permeability magnetic filling agent capable of rapidly and reversibly changing its properties when exposed to an external magnetic field, which makes it a perspective material for application in a wide range of engineering areas. The research has analyzed the trends in the strength properties of the materials obtained through the use of filling agents of different fineness, content, and structural organization in the final polymer, under different conditions. This allowed to obtain the correlations between the influence of the filler's relative fineness on the dynamic and mechanical properties of composite polymers, and to estimate the trends in the parameters describing the material strength under the complex magnetic and thermal influence. The results obtained by the authors allowed to ground the composition and structural organization of the final material with the best set of dynamic and mechanical properties.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015 TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The aims of this study are to measure the technical efficiency (TE) of Cambodian household’s rice production and trying to determine its main influencing factors using the stochastic frontier production function. The study utilized primary data collected from 301 rice farmers in three selected districts of Battambang by structured questionnaires. The empirical results indicated the level of household rice output varied according to differences in the efficiency of the production processes. The mean TE is 0.34 which means that famers produce 34% of rice at best practice at the current level of production inputs and technology, indicates that rice output has the potential of being increased further by 66% at the same level of inputs if farmers had been technically efficient. Furthermore, between 2013-2015, TE of household’s rice production recorded -14.3% decline rate due to highly affected of drought during dry season of 2015. Moreover, evidence reveals that land, fertilizer, and pesticide are the major influencing input factors of household’s rice production, while disaster, education of household head, family size and other crops’ cultivated area are core influencing factors decreasing TE. Conversely, the main influencing factors increasing TE are irrigated area, number of plot area and sex of household head.

The present study aims to measure the technical efficiency and establish core factors effecting rice production in Cambodia. Four-years dataset generated from the central government document “Profile on Economics and Social” of entire 25 provinces between 2012-2015 and the stochastic production frontier model (SFA) was applied. The results indicated that the level of output (quantity) of Cambodian rice production varied according to the different level of capital investment in agricultural machineries, total rice actual harvested area, and technically fertilizers application within provinces. Furthermore, evidence revealed the overall mean efficiency of rice production is 78.4% implies that there is still room to further improve technical efficiency by given the same level of inputs and technology. More importantly, the findings revealed that irrigation, production technique and amount of agricultural supporting staffs are being as the most important influencing factors of rice production’s technical efficiency in Cambodia. In conclusion, present study strongly recommends the development of irrigation systems and good water management practices to be considered and bring into more effective actions by the central government as well as related agencies for improving rice production in Cambodia in addition to capital investment and improving technical skills of supporting staffs and rural farmers.

Cotton is the most ubiquitous and profitable fiber with diverse industrial and domestic applications. Grown in over 100 countries, it has a global market value of about $40 billion and employs over 350 million people from fields to textile mills, contributing about 7% of total labor-force recruitment in developing economies. Cotton has an indeterminate growth habit and an extensive tap root system affected by soil physicochemical and environmental conditions. There is a consensus among experts that conventional cotton cultivation still has a long way to attain sustainability, which is essential if cotton will maintain its competitive edge over other natural and synthetic fibers like hemp, polyesters, and rayon. Despite several efforts already committed to growing cotton sustainably, sustainability has eluded cotton cultivation globally because of the intense farm inputs (freshwater, pesticides, and heavy-duty equipment) needs, especially in developing economies. Some of the technological advancements towards achieving the goal of sustainable cotton cultivation include the development of new varieties, improved irrigation and mulching and precision agriculture techniques, application of remote sensing and Unmanned Aerial Systems (UAS) combined with image processing, and the introduction of autonomous and multi-purpose robotic platforms for growing and harvesting cotton. This review attempts to evaluate the successes already achieved by stakeholders in moving cotton towards sustainable production and identify areas where efforts are still needed to reach sustainable production and improved profitability goals for cotton with projections for future research directions.

A Pt(II) complex featuring chelating tridentate bis-aryloxide tetrahydropyrimidinium based N-heterocyclic carbene (NHC) was synthesized and characterized by using different techniques. The electrochemical properties of the complex were investigated by cyclic voltammetry as well as differential pulse voltammetry, which revealed two reversible one-electron oxidation processes. The chemical generation and isolation of one-electron-oxidized species were performed oxidizing the initial complex by means of AgBF4. The combined UV-Vis/NIR- and EPR-spectroscopy studies supported by density functional theory (DFT) calculations suggest the formation of Pt(II)-phenoxyl radical complex. The latter open-shell derivative was structurally characterized by means of X-ray diffraction analysis. Finally, the neutral platinum complex was tested as a mediator in the process of electrocatalytic oxidation of 2-(methylamino)ethanol (MEA).

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

The successful vaccination implies the induction of effective specific immune responses. We intend to find biomarkers among various immune cell subpopulations, cytokines and antibodies which could be used to predict the levels of specific antibody- and cell-mediated responses after measles-mumps-rubella vaccination. We measured 59 baseline immune status parameters (frequencies of 42 immune cell subsets, levels of 13 cytokines, immunoglobulins) before vaccination and 13 response variables (specific IgA and IgG, antigen-induced IFN-γ production, CD107a expression on CD8+ T lymphocytes, and cellular proliferation levels by CFSE dilution) 6 weeks after vaccination for 19 individuals. Statistically significant Spearman correlations between some baseline parameters and response variables were found for each response variable (p&lt;0.05). Due to the low number of observations relative to the number of baseline parameters and missing data for some observations, we utilized three feature selection strategies to select potential predictors of the post-vaccination responses among baseline variables: (a) screening of the variables based on the correlation analysis, (b) supervised screening based on the information of changes of baseline variables at day 7, (c) implicit feature selection is performed using regularization-based sparse regression. We identified optimal multivariate liner regression models for predicting the effectiveness of vaccination against measles-mumps-rubella using the baseline immune status parameters. It turned out that the sufficient number of predictor variables ranges from one to five depending on the response variable of interest.

Cuboid diamonds are particularly common in the placers of the northeastern Siberian platform but their origin remains unclear. These crystals usually range in color from dark yellow to orange and more interestingly, are characterized by unusual low aggregated nitrogen impurities (non-aggregated C-center) suggesting a short residence time and/or low temperatures at which they have been stored in the mantle. In order to track possible isotopic signature that could help deciphering cuboid diamond's crystallization processes, δ¹³C values, δ¹⁵N values and nitrogen contents have been determined in-situ in three samples using secondary ion mass spectrometry (SIMS), whereas nitrogen aggregation state have been determined by FTIR spectroscopy. The samples fall out the δ¹³C vs. δ¹⁵N field of canonical mantle composition. Different scale of carbon and nitrogen fractionation may produce the observed variations. Alternatively, mixing of mantle and crustal material would obscure initial co-variations of δ¹³C values with δ¹⁵N or nitrogen content.

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.

Chemical versatility of organic semiconductors provides nearly unlimited opportunities for tuning their electronic properties. However, despite decades of research, relationship between molecular structure, molecular packing and charge mobility in these materials remains poorly understood. This reduces the search for high-mobility organic semiconductors to the inefficient trial-and-error approach. For clarifying the abovementioned relationship, investigations of the effect of small changes in the chemical structure on OSs properties are particularly important. In this study, we address computationally the impact of substitution of C-H atom pairs by nitrogen atoms (N-substitution) on molecular properties, molecular packing and charge mobility of crystalline oligoacenes. Besides of decreasing frontier molecular orbital levels, N-substitution dramatically alters molecular electrostatic potential yielding pronounced electron-rich and electron-deficient areas. These changes in the molecular electrostatic potential strengthen face-to-face and edge-to-edge interactions in the corresponding crystals and result in the crossover from the herringbone packing motif to π-stacking. When the electron-rich and electron-deficient areas are large, sharply defined and, probably, have certain symmetry, charge mobility increases up to 3-4 cm2V-1s-1. The results obtained highlight the potential of azaacenes for application in organic electronic devices and are expected to facilitate rational design of organic semiconductors for steady improvement of organic electronics.

Revealing the spatial distribution mechanism of the coupling effect between soil water and salt is essential for managing saline-alkali farmland. This study utilized the multifractal method to analyze soil water and salt under varying water content levels in arid saline-alkali farmland. Soil samples were collected on the second (S1), fifth (S2), eighth (S3), eleventh (S4), and fourteenth (S5) days after a rainfall event. The findings showed that a significant decrease in soil water content, contrasting with an increase in soil salt content throughout the soil layers post-rainfall. As water content decreased, the spatial variability of soil water initially increased from S1-3 and then decreased, while the spatial variability of soil salt decreased. The spatial distribution between soil water and salt exhibited a high correlation at S3-4 (with relative water content of soil ranging from 0.52 to 0.75) due to their coupling effect. However, soil salt was unevenly leached by rainfall at high water content levels (S1-2) and precipitated at low water content levels (S5), resulting in low spatial variability correlations between soil water and salt. This study elucidated the coupling process of soil water and salt, identifying their spatiotemporal distribution mechanism in dryland agricultural areas.

The spatial and temporal variability in dietary preferences of juvenile three-spined stickleback Gasterosteus aculeatus, was studied across typical coastal habitats of Keret Archipelago, Kandalaksha Bay, the White Sea. Sampling of fish using beach seine was implemented in late July-early August and in late August, and zooplankton samples were collected to make a quantitative evaluation of abundance of potential prey items. Similarity Percentage (SIMPER) analysis implemented over the data obtained from stomach content analysis revealed five planktonic taxa mostly contributing to the diet of juvenile sticklebacks, of which copepod Temora longicornis was the most important prey item at marine sites, while Acartia longiremis prevailed in diet of fishes in marine lagoon. Calculation of selectivity index demonstrated that some taxa (e.g., A. longiremis) were always avoided by juvenile fishes, others (e.g. Microsetella norvegica) were firstly avoided and then selected in late August. Calculation of selectivity index was implemented per sample and per individual fish indicated that taxa like T. longicornis and were selected during the whole period of study, fishes demonstrated pronounced individual variation in prey selectivity. In general, data on selectivity indicated that despite juvenile sticklebacks feed on mostly available prey items, they can demonstrate taxonomic and size-specific prey selectivity.

Recent years witnessed progressive broadening of the practical use of 3D-printed aluminium alloy parts, in particular for specific aerospace applications where weight saving is of great importance. Selective laser melting (SLM) is an intrinsically multi-parametric fabrication technology that offers multiple means of controlling mechanical properties (elastic moduli, yield strength, ductility) through the control over grains size, shape, and orientation. Ultimately, this approach implies that structural elements can be purposefully fabricated to reinforce specific zones and directions where higher mechanical loads are anticipated by design. Targeted control over mechanical properties is achieved through the tuning of 3D-printing parameters and may even obviate the need of heat treatment or mechanical post-processing. Systematic studies of grain structure for different printing orientation with the help of EBSD techniques in combination with mechanical testing at different dimensional levels are the necessary first steps to implement this agenda. Samples of 3D-printable Al-Mg-Si RS-333 alloy were fabricated in 3 orientations with respect to the principal build direction and the fast laser beam scanning direction. Sample structure and proper-ties were investigated using a number of techniques, including EBSD, in situ SEM tensile testing, roughness measurements and nanoindentation. The as-printed samples we found to display strong variation in Young’s modulus values from nanoindentation (from 43 to 66 GPa) and tensile tests (from 54 to 75 GPa), yield stress and ultimate tensile strength (100…195 and 130…220 MPa) in different printing orientations, and almost constant hardness of about 0.8 GPa. A further preliminary study was conducted of the effect of surface finishing on the mechanical performance. Surface polishing appears to reduce Young’s modulus and yield strength, but improves ductility, whereas the influence of sand blasting is more controversial. The experimental results are dis-cussed in connection with the grain morphology and orientation.

We observed and studied the phenomenon of the redox front propagation in different polyaniline (PAni) deposited samples interfaced with liquid or solid polymeric electrolyte. The front of electrochemical conversion, in which the insulator and the conductor parts of PAni are interfaced, is studied observing the temporal evolution of the conductivity of PAni samples. The propagation of redox front was studied in electrochemically obtained thick (2 µm) and in thin (50 nm) poly-aniline films, obtained using Langmuir-Blodgett (LB) method. In the configuration that we tested, the speed of the red-ox front propagation for the thin LB films was found to be 200 micron/sec opening the way for the manufacturing large neural networks, realized using PAni based memristive devices, in which the memristance can be quickly changed in the programmable manner. The prototypes of the spiking neuron connections were manufactured on the basis of lithographically developed gold contacts, bridged by electrochemically grown polyaniline and placed under polymer electrolyte layer with only one counter electrode (gate) for the whole manifold of pseudo-two-terminal memristor bridges. The spike propagation was studied in such gold-polyaniline systems. The research opens the possibility of miniature spike or rate-based neural network circuits manufacture, based on metal pads and polyaniline.

The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated in the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Electrospun ultrathin fibers based on binary compositions of polylactide (PLA) and poly(ε-caprolactone) (PCL) with different ratios of polymer components from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the effect of biopolymers content on the characteristics of the crystal structure of PLA and PCL and the diffusive rotational mobility of the stable TEMPO radical in the amorphous regions of PLA/PCL compositions was shown. It was revealed that after PLA and PCL blending, significant changes in the degree of crystallinity of PLA, PCL segmental mobility, sorption capacity of the radical as well as activation energy of rotational diffusion in the amorphous regions of PLA/PCL composition are observed. The characteristic region of biopolymers’ composition from 50/50 to 30/70 % PLA/PCL blends ratio was found, where the inversion transition of PLA from dispersive medium to dispersive phase where an inversion transition is assumed when the continuous medium of the PLA transforms into a discrete phase. The performed studies made it possible for the first time to carry out a comprehensive analysis of the effect of the system component ratio on the structural and dynamic characteristics of the PLA/PCL film material at the molecular level.

The manuscript presents the comprehensive integrative theory of the etiology and pathogenesis of Alzheimer’s disease - the amyloid degradation toxicity hypothesis - and describes the logic that underlies it.The analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies suggest that AD diagnosis is associated with higher cellular uptake of beta-amyloid. Uptake of beta-amyloid by cells is needed for its cytotoxicity, so the uptake rate should correlate with the rate of neurodegeneration. Also, the initial step in forming extracellular aggregates cannot occur in the interstitial fluid due to the extremely low concentration of beta-amyloid but can occur intralysosomally. Therefore, the density of extracellular aggregates should positively correlate with the rate of cellular amyloid uptake. The model, which considers that both cytotoxicity and aggregation of beta-amyloid are defined by cellular uptake, successfully reproduces the probability distribution of AD diagnosis in the population. Cellular uptake of beta-amyloid is mediated by endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage. Lysosomal permeabilization explains ion disturbances, such as an accumulation of intracellular calcium, caused by cell exposure to extracellular beta-amyloid. Some amyloid fragments, produced from beta-amyloid by lysosomal proteases, can form membrane channels in lysosomal membranes, which are large enough to leak cathepsins to the cytoplasm. Appearance of proteases in the cytoplasm results in necrosis and/or initiation of apoptosis. If the cell survives, the damage of lysosomes leads to autophagy failure and slow recycling of mitochondria, promoting the production of reactive oxygen species and potentiating cell damage.Considering the above, the integrative theory of AD etiology and pathogenesis can be formulated. The etiology of AD is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization by giant membrane channels, which leak lysosomal proteases into the cytoplasm. The correlation between the density of amyloid aggregates and the probability of AD appears because the intensity of cellular uptake defines both aggregation rates in vivo and cytotoxicity of beta-amyloid.The amyloid degradation toxicity hypothesis is the integrative theory of Alzheimer’s disease (AD). It successfully interprets multiple phenomena and paradoxes associated with AD pathobiology at various levels, from molecular and cellular to biomarkers. The hypothesis explains the limitations of currently used biomarkers of AD and proposes etiology-related parameters. These parameters could be measured in humans and become novel diagnostic and prognostic clinical tools. Based on the proposed framework, we foresee the development of effective medications to treat, stall the progression of, or prevent disease development.

Electron can tunnel between cofactor molecules positioned along biological electron transport chains up to the distance of ≃20 Å on the millisecond time scale of enzymatic turnover. This tunneling range mostly determines the design of biological energy chains facilitating cross-membrane transport of electrons. Tunneling distance and cofactors’ redox potentials become main physical parameters of this design. The protein identity, flexibility, or dynamics are missing from this picture assigning universal charge-transport properties to all proteins. This paradigm is challenged by dynamical models of electron transfer showing that the hopping rate is constant within the crossover distance R*≃12 Å, followed with an exponential tunneling falloff at longer distances. In this view, energy chains for electron transport are best designed by placing redox cofactors near the crossover distance R*. Protein flexibility and dynamics affect the magnitude of the maximum hopping rate within the crossover radius. Protein charge transport is not driven by universal parameters anymore and protein identity matters.

In this manuscript, we reassess the data on beta-amyloid-induced changes of intracellular ions concentrations published previously by Abramov et al. (2003, 2004). Their observations made using high-resolution confocal microscopy with fast temporal resolution of images formed by fluorescent ion-sensitive fluorescent probes in living cells represent an unequivocal support for the amyloid channel theory. However, closer look reveals multiple facts which cannot be explained by channel formation in plasma membrane. Recently proposed amyloid degradation toxicity hypothesis provides the interpretation to these facts by considering that channels are formed in the lysosomal membranes.

A Staudinger reaction on solid phase between an electronodeficit organic azide such as sulfonyl azide, and the phosphite triester formed upon phosphoramidite coupling is a convenient method for chemical modification of oligonucleotides at the internucleotidic phosphate position. In this work, 4-carboxybenzenesulfonyl azide either with a free carboxy group or in the form of an activated ester such as pentafluorophenyl, 4-nitrophenyl, or pentafluorobenzyl ester were used to introduce a carboxylic acid function to the terminal or internal internucleotidic phosphate of an oligonucleotide via Staudinger reaction. A subsequent treatment with excess primary alkyl amine followed by usual work-up, after prior activation with a suitable peptide coupling agent such as HBTU/HOBt in the case of a free carboxyl, afforded amide-linked oligonucleotide conjugates in good yields including multiple conjugations of up to the exhaustive modification at each phosphate position for a weakly activated pentafluorobenzyl ester, whereas more strongly activated and, thus, more reactive aryl esters provided only single conjugations at the 5′-end. The conjugates synthesized include those with di- and polyamines that introduce a positively charged side-chain to potentially assist intracellular delivery of the oligonucleotide.