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Among the current priorities for the development of the Russian oil and gas complex, which determine its competitiveness in the international hydrocarbon market, are its capabilities and the pace of its decarbonization. The development of decarbonization processes at the present requires the solution of a number of scientific, methodological and applied problems. Based on the results of a review of modern domestic and foreign approaches, methodological provisions are substantiated that determine the content and structure of the decarbonization category in the oil and gas complex. Decarbonization in the world economy system is defined as a systemic response to planetary climate change. In the system of the national economy (energy) — as a long-term socio-economic trend (pattern) of reducing the carbon intensity of GDP. In the system of the oil and gas complex — as a systemic process of its transformation in the national energy sector. In the system of industry management — as a process of complex, interconnected use of diverse (including fundamentally new) methods of solutions and technologies from various industries and fields of knowledge. Based on a systematic analysis of the problem field, the strategic goals and priorities for the development of the oil and gas complex have been clarified within the framework of the low-carbon development paradigm in the global energy system. The methods and tools of existing and being in the development and approval legislative documents have been studied. We proposed an approach to the formation of organizational and economic mechanisms that ensure the effective and sustainable development of the oil and gas complex in the context of decarbonization.

Taking these prospects into account, the integration potential of Russia in the conditions of gradual trade and economic unity of the ASEAN countries can be considered in the aspect of formation of new strategic opportunities for interaction with the integration environment of Eurasia on the basis of investments in infrastructure development within the framework of the Eurasian Economic Union (EAEU). The advantages and disadvantages of the digital platforms and the characteristic features of international DLPs are highlighted. Based on the analysis, the necessity of developing an international digital platform in the EAEU is justified in the context of the development of international digital logistics platforms within the framework of the Eurasian Economic Union.

SummaryIcumazoles are potent antifungal polyketides with intriguing structural features. Here, we present the polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid biosynthetic gene cluster of icumazoles. Surprisingly, an unusual non-terminal thioesterase domain divides the PKS/NRPS assembly line. The succeeding PKS modules potentially form a rare precursor 4-methyl-2-hexenoyl-ACP thus deviating from the previously proposed polyoxypeptin pathway. The 4-methyl-2-hexenoyl-ACP is further reductive carboxylated to 2-methylbutylmalonyl-ACP essential for icumazole biosynthesis by IcuL, representing a new type of crotonyl-CoA carboxylase/reductase (CCR). We characterize IcuL and its homologs TgaD and Leu10in vitro, suggesting a stricter substrate specificity of this new family of CCRs than found in canonical ones. Intriguingly, we also find that TgaD unprecedently utilizes both NADPH and NADH as cofactors with similar efficiency, diverging from the NADPH-specific characteristic of canonical CCRs. Furthermore, a sequence similarity network-based bioinformatic survey reveals that the IcuL-like CCRs are evolutionarily separated from canonical CCRs.

Hypercytokinemia, found in SARS-CoV-2 infection, contributes to multiple organ dysfunctions with acute respiratory distress syndrome, shock etc. The aim of this study was to describe cytokine storm signatures in patients with acute COVID-19 and to investigate their influence on severity of the infection. Plasma levels of 47 cytokines were investigated in 73 patients with moderate and severe COVID-19 (41 and 32, respectively) and 11 healthy donors (HD). The most elevated levels comparing patients and the HD were observed for seven pro-inflammatory cytokines (IL-6, IL-8, IL-15, IL-18, IL-27, IFNγ, TNFα), three chemokines (GROα, IP-10, MIG), two anti-inflammatory cytokines (IL-1RA, IL-10), and two growth factors (G-CSF, M-CSF). The patients with severe disease had significantly higher levels of FGF-2/FGF-basic, IL-1β, and IL-7 compared to the HD. The two groups of patients differed from each other only based on the levels of EGF, eotaxin, and IL-12 p40. Pneumonia lung injury, characterized by computer tomography, positively correlated with levels of EGF, IP-10, MCP-3 levels and negatively with IL-12 p40. Pro-inflammatory factors including IL-6, TNFα, and IP-10 negatively correlated with the frequency of the circulating T-helper17-like cells (Th17-like) and follicular Th cells that are crucial to develop SARS-CoV-2-specific plasma cells and memory B cells. Obtained data on the cytokine levels illustrate their influence on progression and severity of COVID-19.

The article discusses the activities of energy service companies, which is aimed at saving energy resources and improving energy efficiency. The article also discusses the sources of investment projects of energy service companies and what specific services are provided by energy service companies. Schemes of logistic chains have been built, the links of which are the customer, energy service company, bank / investor, resource provider, consumer / customer. We propose to improve the model of the logistics chain. The traditional logistics chain is a linear-ordered set of legal entities and individuals that perform logistics functions and operations to conduct material and information flows from the supplier to the consumer. That is, we understand that the links of a simple logistics chain follow each other, thus the links of the chain can contact and perform any actions only in such a sequence. Due to the approach of the traditional logistics chain, problems arise, since the information may reach in a distorted state, or it may not reach at all. We suggest logistics approach to energy service management based on the principles of digital approaches which could be developed from the famous research papers of A. Borovkov. This model is interesting because the analytical center acts as the core in this chain, which translates the information received for everyone. Conclusions are drawn on the relationship between energy conservation, quality and investment. Attention is paid to finding a new approach to energy service from the concept of digital core in logistics network.

MicroRNAs, as small non-coding regulatory RNAs, play crucial roles in various aspects of breast cancer biology. They have prognostic and diagnostic value, which makes them very interesting molecules to investigate. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is the gold standard method to analyse miRNA expression in breast cancer patients. This study investigated two RT-qPCR methods (absolute and relative) to determine the expression of ten miRNAs in whole blood samples obtained from luminal A breast cancer patients compared to healthy controls. Whole blood samples were collected from 38 luminal A breast cancer patients and 20 healthy controls in Paxgene blood RNA tubes. Total RNA was extracted and analysed by relative and absolute RT-qPCR. For relative RT-qPCR, miR-16 was used as an endogenous control. For absolute RT-qPCR, standard curves were generated using synthetic miRNA oligonucleotides to determine the absolute copy number of each miRNA. Of the ten miRNAs that were analysed, the absolute RT-qPCR method identified six miRNAs (miR-16, miR-145, miR-155, miR-451a, miR-21 and miR-486) that were upregulated and one miRNA (miR-195) that was downregulated. ROC curve and AUC analysis of the data found that the combination of three miRNAs (miR-145, miR-195 and miR-486) had the best diagnostic value for luminal A breast cancer with an AUC of 0.875, with 76% sensitivity and 81% specificity. On the other hand, the relative RT-qPCR method identified two miRNAs (miR-155 and miR-486) that were upregulated and miR-195, which was downregulated. Using this approach, the combination of three miRNAs (miR-155, miR-195 and miR-486) was showed to have an AUC of 0.657 with 65% sensitivity and 69% specificity. We conclude that miR-16 is not a suitable normalizer for the relative expression profiling of miRNAs in luminal A breast cancer patients. Compared to relative quantification, absolute quantification assay is a better method to determine the expression level of circulating miRNAs in Luminal A breast cancer.

Breast cancer is stratified into four distinct clinical subtypes, using three key biomarkers (Her2/Neu gene status, Estrogen and Progesterone receptor status). However, each subtype is a heterogeneous group, displaying significant variation in survival rates and treatment response. New biomarkers are required to provide more precise stratification of breast cancer cohorts to inform personalised treatment options/predict outcomes. Tip60 is a member of the MYST sub-family of histone acetyltransferases (HATs), and is directly involved in genome maintenance, gene regulation and DNA damage response/repair pathways (key chemotherapeutic influencing mechanisms). We aimed to determine if quantifying Tip60 staining patterns improved breast cancer stratification. We defined Tip60 protein in vivo, quantifying location (cytoplasmic, nuclear), percent of cells and staining intensity in a breast cancer tissue microarray (n = 337). A significant association of specific Tip60 staining patterns with breast cancer subtype, ER or PR status and Tumour grade was found. Importantly, low Tip60 mRNA expression correlated with poor overall survival and relapse free survival. We found Tip60 is a biomarker able to stratify breast cancer patients, and low Tip60 expression is a significant risk factor indicating a higher chance of disease reoccurrence. This work highlights Tip60 regulation as a key factor influencing the development of breast cancer.

This article substantiates the need to form a comprehensive system of professional development and assessment of teachers’ competencies in order to ensure quality education in the interests of sustainable development of society. The main goals and objectives are formulated and the methodological tools developed by the authors for the formation of this system are described. The features of the implementation of the system in the practice of conducting the educational process at Peter the Great St. Petersburg Polytechnic University (St. Petersburg, Russia) are revealed. The risks are identified and recommendations for their minimization are given for other educational organizations of higher education that implement a comprehensive system of professional development and assessment of the competencies of teachers using digital services.

COVID-19 struck the world, and nothing has remained the same. The various industries of the world can attest to how much effect the abrupt disruption amounted to their various sectors and how much it affected them in terms of revenue generation, human resources, and flow of operation. Although some were eventually able to gain their footing by being able to leverage technological solutions, tourism felt the brunt of the pandemic as the operations were brought to a sudden halt, and the tourism sector found it very challenging to cope. Many were let off their jobs, and what used to be a great source of revenue generation for several economies suffered a great loss. The pandemic without any doubt served as a wakeup call to the reality of the not-so-effective state of the tourism sector. Technology brought about the solutions with which other industries withstood the ravaging challenges of the pandemic. The digital world is the new normal for the world, and for the tourism industry to grow, it must find the best way to leverage technological solutions.

This paper investigates the effects of digital production and information technologies on the development of logistic systems of different kinds: megalogistic, macrologistic, and micrologistic. The notions of a logistic system and types of logistic systems imply that logistics is considered in its broad sense as a modern methodology for managing all types of flows that appear in the process of socioeconomic activities of society and business: material, information, energy, financial and labor flows. The methodology discussed in this paper gives the answer to the question of what impact digital production and information technologies have on the development of various types of logistic systems. The methodology includes building a mathematical model in which the endogenous variables of the model reflect the resulting variables of the logistic system, while the exogenous variables reflect digital production and information technologies. The mathematical model is a system of interdependent dynamic econometric equations. Each equation is an autoregressive distributed lags model. In the model, the current values of an endogenous variable depend on their previous values, as well as on the current and previous values of other endogenous and exogenous variables. The novelty of the research is in the developed methodology for a comprehensive assessment of the impact made by digitalization on a totality of the interrelated and interdependent resulting indicators of the logistic system. A comprehensive assessment of the impact made by digitalization on a totality of interrelated and interdependent indicators of the logistic system is understood as a change in the indicators of the logistic system due to the effect of digitalization. The proposed methodology for a comprehensive assessment was empirically tested for Salesforce company.

Graft versus host disease (GVHD) is a severe, often lethal, complication of hematopoietic stem cell transplantation, and although prophylactic regimens are given as standard pre-transplantation therapy, up to 60% of these patients develop aGVHD, and require additional immunosuppressive intervention. Previously we showed that treatment of mice with a purified probiotic molecule, exopolysaccharide (EPS) from Bacillus subtilis, significantly increased survival of GVHD mice compared to control PBS-treated mice (70% vs 10%, respectively), with EPS-treated mice surviving more than 100 days after aGVHD induction. To test if EPS can also ameliorate GVHD in humans, we used humanized NSG-HLA-A2 mice and induced GVHD by i.v. injection of HLA-A2neg human PBMCs. After deriving dendritic cells (DC) from CD34+ cord blood cells, we pretreated them with EPS or PBS, and injected them together with PMBCs into the NSG-HLA-A2 mice. We found that EPS-treated DC significantly prolonged the survival of these mice, compared to PBS-treated DC. We also found that EPS-treated DC downregulated expression of activation markers (CD80, CD86), upregulated expression of inhibitory molecules (PD-L1, PD-L2), and inhibited activation of alloreactive T cells in MLR. We conclude that EPS induces tolerogenic human DC, which ameliorate GVHD in humanized NSG-HLA-A2 mice, likely by inhibiting alloreactive T cell response. Supported by NIH R41 AI155281

Acute graft-versus-host disease (aGvHD) is a severe, often lethal, complication of hematopoietic stem cell transplantation, and although prophylactic regimens are given as standard pretransplantation therapy, up to 60% of these patients develop aGvHD, and require additional immunosuppressive intervention. We treated mice with a purified probiotic molecule, exopolysaccharide (EPS) from Bacillus subtilis, shortly before and after induction of aGvHD and found that, whereas only 10% of control mice survived to day 80, 70% of EPS-treated mice survived to 80 d. EPS treatment of donor-only mice resulted in ∼60% survival. Using a biosensor mouse model to assess inflammation in live mice during aGvHD, we found that EPS prevented the activation of alloreactive donor T cells. In vitro, EPS did not affect T cells directly but, instead, induced bone marrow–derived dendritic cells (BMDCs) that displayed characteristics of inhibitory dendritic cells (DCs). Development of these BMDCs required TLR4 signaling through both MyD88 and TRIF pathways. Using BMDCs derived from IDO knockout mice, we showed that T cell inhibition by EPS-treated BMDCs was mediated through the suppressive effects of IDO. These studies describe a bacterial molecule that modulates immune responses by inducing inhibitory DCs in a TLR4-dependent manner, and these cells have the capacity to inhibit T cell activation through IDO. We suggest that EPS or EPS-treated DCs can serve as novel agents for preventing aGvHD.

Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce tumour burden prior to surgical resection. However, only a subset of NACT treated patients will respond to treatment or achieve a pathologic complete response (pCR). This multicenter, prospective study (CTRIAL-IE (ICORG) 10-11 study) evaluated circulating microRNA as novel non-invasive prognostic biomarkers of NACT response in breast cancer. Selected circulating microRNAs (Let-7a, miR-21, miR-145, miR-155, miR-195) were quantified from patients undergoing standard of care NACT treatment (n = 114) from whole blood at collected at diagnosis, and the association with NACT response and clinicopathological features evaluated. NACT responders had significantly lower levels of miR-21 (p = 0.036) and miR-195 (p = 0.017), compared to non-responders. Evaluating all breast cancer cases miR-21 was found to be an independent predictor of response (OR 0.538, 95% CI 0.308&ndash, 0.943, p &lt, 0.05). Luminal cancer NACT responders were found to have significantly decreased levels of miR-145 (p = 0.033) and miR-21 (p = 0.048), compared to non-responders. This study demonstrates the prognostic ability of miR-21, miR-195 and miR-145 as circulating biomarkers stratifying breast cancer patients by NACT response, identifying patients that will derive the maximum benefit from chemotherapy.

Physiological and morphological studies of red Russian and foreign breeding red currant varieties were carried out for establishing intensive plantings and introduction. Varieties Dana, Niva, Vika, Hollandische Rote are yielding, highly resistant and promising for introduction and industrial cultivation, during dry periods they are able to regulate metabolism through changing indicators of water balance (water deficit, fractional composition of water) and photosynthetic apparatus of leaves (leaf lamina area). Using Natali, Shchedraya and Jonkheer Van Tets varieties in production is possible with application of artificial irrigation. Selyanochka variety is most affected by weather conditions and is recommended to be grown in temperate climate area. Physiological and morphological methods of research allow to diagnose the genotypes resistance of garden crops to growing period abiotic factors at the early stages of plant development, they are confirmed by field observations and are promising in diagnosis for establishing intensive gardens and berry-fields.

Digitalization of all economic sectors results in continuously increasing load on corporate data processing centers. There is decrease of economic efficiency for using classic methods of developing information infrastructures of organizations. The purpose of this article is to provide the non-classical description of the current situation in the IT development conceptual field and the conceptual description of the intellectual computing platform of modern organization in the digital globalization context.

This paper discusses the importance and methods of Human Resource management in the high-technology companies of the Travel, Transport and Logistic industry. The qualification and motivation of the employees is a key factor of increasing the effectiveness and competitiveness of the big marker players. In this study the particular attention is paid to the digital tools and software to optimize and improve the quality of the HR business processes. As a result of this study, it was found that information technologies can reduce the time of the recruiting and hiring processing and present the detailed analytics on the workforce to the executive management. It would be interesting to consider the impact of investments in HR business process optimization on the general effectiveness of the transportation industry.

Undoubtedly, the organizations need to be flexible and able to continuously improve business processes with the relevant measures intended for organizing staff. The purpose of the research is to propose methodology for economic evaluation of operational projects of personnel management based at crises enterprises on the mechanism for making managerial decisions on the effective systems of remuneration in a digital environment. The authors’ studies have shown that when enterprises are withdrawn from crisis situations, operational projects are mainly implemented, not investment ones. This fully applies to personnel management projects. The important thing here is that the funds for their implementation are significantly limited, and there are a lot of options for such projects when developing enterprise development plans. A feature of operational projects is that they are usually financed from funds from the company’s turnover; accordingly, they need a quick return, i.e. minimum payback. Personnel management operational projects could be defined as diverse and multidirectional regarding automation and staff planning, determining the need for hiring personnel, selecting and hiring employees, their training and adaptation, organizing career opportunities, attesting and evaluating the performance of job functions, motivation, employee incentives, organizing payments and labor rationing. This list of elements of the personnel management system can be supplemented and expanded. Therefore, the selection of the most effective projects for crisis enterprises requires a methodology for economic evaluation of just such operational projects to improve personnel management system. The proposed methodology for economic evaluation of operational projects of personnel management of different organizations and enterprises includes three main types of work, including localization of the project with the advantages and disadvantages of events being identified, as well as the establishment and calculation of criteria for cost and effectiveness of measures for the company as a whole, and, finally, the development of a mechanism and quantitative calculation of changes in risks in the enterprise.

The modern foreign and domestic studies consider the digital transformation of the economy mostly as a combination of effects arising under the influence of a number of implemented digital innovations, which result in the emergence of new economic structures, new business practices, as well as new values and beliefs in the business environment. The article is devoted to the research of logistics networks development features in the context of globalization and digitalization of the economy. Issues of increasing the efficiency of the functioning of logistics networks using digital technologies through the creation of information logistics platforms also considered. As the scientific novelty of the study, it should be noted the highlighted advantages of digitalization of logistics platforms. The digital economy, in which modern logistics networks operate, is characterized by the following main features the global nature, the use of network principles for coordinating society and markets, operations with intangible benefits: information and relationships, ideas. Modern management of international logistics systems is based on the integration of digital control in the system of automatic regulation and control of the road situation and the transport situation. Thus, within the framework of the platform economy, there is a complete transformation of the existing business models. The authors prove that the features of logistics digitalization cause a significant impact on the process of logistics networks development with the necessary theoretical and methodological support for the design process of international trading.

Fitness conferred by the same allele may differ between genotypes and environments, and these differences shape variation and evolution. Changes in amino acid propensities at protein sites over the course of evolution have been inferred from sequence alignments statistically, but the existing methods are data-intensive and aggregate multiple sites. Here, we develop an approach to detect individual amino acids that confer different fitness in different groups of species from combined sequence and phylogenetic data. Using the fact that the probability of a substitution to an amino acid depends on its fitness, our method looks for amino acids such that substitutions to them occur more frequently in one group of lineages than in another. We validate our method using simulated evolution of a protein site under different scenarios and show that it has high specificity for a wide range of assumptions regarding the underlying changes in selection, while its sensitivity differs between scenarios. We apply our method to the env gene of two HIV-1 subtypes, A and B, and to the HA gene of two influenza A subtypes, H1 and H3, and show that the inferred fitness changes are consistent with the fitness differences observed in deep mutational scanning experiments. We find that changes in relative fitness of different amino acid variants within a site do not always trigger episodes of positive selection and therefore may not result in an overall increase in the frequency of substitutions, but can still be detected from changes in relative frequencies of different substitutions.

The aim of the research was to study the offspring from the open pollination of ES 1674-30-30 by the main economically important traits for the crop and to isolate valuable genotypes. During the record, it was revealed that some seedlings inherited from the parent form a trait of apical fruiting. Of the 79 seedlings of such atypical plants, there were 18 seedlings, which was 23.7%. In all years of the observation, the average raceme length for the group of seedlings with apical fruiting exceeded the average for typical seedlings of this family. There were no significant differences in the weight of 100 berries between the groups of seedlings. It was found that plants with apical fruiting aged faster than ordinary seedlings. As a result of the research, it was found that the family 2521 was of breeding value for the yield of long-raceme seedlings resistant to fungal diseases.

This chronosequential study focuses on the vegetation succession, Luvisol pedogenesis, and long-term carbon dynamics during post-agricultural restoration in the temperate broad-leaved forest of European Russia. The study comprises three chronosequences of 37 years (North), 120 years (Middle), and 42 years (South) to cover climatic differences within the study area. The sites of each catena were mostly comparable in terms of climate, soil texture, and land history, but the duration of agricultural abandonment differed between sites. Plant succession developed via a birch forest or a pear-ash woodland to a birch-oak forest with Aegopodium podagraria after 120 years, which indicates the plant association is near to a climax oak forest. Former homogenous plow horizons formed a new morphological stratification similar to natural Luvisols, due to the formation of a well rooted Ah horizon and an O horizon of mull; a change in soil structure from coarse blocky to granular; and decreasing bulk densities. However, plow features were identified even after 120 years of Luvisols restoration. During restoration, the former plow horizons showed minor changes of pH 5.4–5.6 (CaCl2). However, a slightly increased pH value within the newly developed Ah and O horizons induced a new pH stratification of the former plow horizon, approaching the natural soils. Compared to the former plow horizons below, soil organic carbon (SOC) and plant available nutrients (P, K) enrichment was observed within the newly developed Ah horizons. The SOC stocks of the 5 cm mineral topsoil increased from 0.8 to 1.7 kg m−2 (North), from 1.3 to 1.7 kg m−2 (Middle), and from 1.4 to 2.3 kg m−2 (South) during restoration. The surface organic layers showed SOC stocks of 0.1–0.2 kg m−2. However, the levels of the near-natural soils were not reached after 37 years (North) and 42 years (South) of restoration. The model predicted a recovery time of about 150 years to achieve a comparatively steady state. A negative effect of mowing was observed for the modelled SOC accumulation. Despite all these alterations, the study showed no full restoration for many parameters within the chronosequential timescale of 120 years.

The theoretical approach of the knowledge economy to the development of the strategy of industrial enterprises on the basis of the logistical methodology are covered. The definition of strategy and strategic planning for the knowledge economy is presented. The process of strategy development is characterized and the algorithm of strategic planning of an industrial enterprise is proposed taking into account the knowledge economy.