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Heterozygosity of Human leukocyte antigen (HLA) class I genes is linked to beneficial outcomes after HIV infection, presumably through greater breadth of HIV epitope presentation and cytotoxic T cell response. Distinct allotype pairs, however, differ in the extent to which they bind shared sets of peptides. We developed a functional divergence metric that measures pairwise complementarity of allotype-associated peptide binding profiles. Greater functional divergence for pairs of HLA-A and/or HLA-B allotypes was associated with slower AIDS progression and independently with enhanced viral load control. The metric predicts immune breadth at the peptide level rather than gene level and redefines HLA heterozygosity as a continuum differentially affecting disease outcome. Functional divergence may affect response to additional infections, vaccination, immunotherapy, and other diseases where HLA heterozygote advantage occurs.

Density functional theory (DFT) is indubitably the most popular and among the most successful approaches for approximately solving the many-electron Schro¨dinger equation. The level of understanding on the part of both researchers and students using DFT, however, is lacking, given the availability of black-box software. The present work addresses this knowledge gap by providing three Jupyter notebooks, easily accessible through the Google Colaboratory (GitHub repository: https://github.com/tjz21/DFT_PIB_Code), that provide a short skirmish with the fundamentals of DFT through a particle in a box-type model system. These notebooks were tested in conjunction with a problem worksheet in a graduate-level quantum chemistry course; pre- and post activity survey results reveal largely positive reactions to this implementation and sustained enthusiasm for the subject.

In the study, the optimal values of the ratio of the distance between particles to the particle size in the radiation-heterogeneous radiolysis of water in nano-Me and nano-MeO systems were determined. In those systems, the effect of water density and system temperature on the radiation-chemical release of molecular hydrogen obtained from thermal and radiation-thermal decomposition of water was considered. The article also determined the effect of particle sizes and the type of sample taken on the radiation chemical yield of molecular hydrogen. In the presented article, the change of molecular hydrogen according to adsorbed water and catalyst was studied. Thus, in the case of a suspension of nano-zirconium in water, the energy of electrons emitted from the metal is completely transferred to water molecules, which leads to an increase in the yield of hydrogen. When radiolysis of water in the presence of nano-metals, energy transfer can be carried out mainly with the participation of emitted electrons. Therefore, in the case of radiolysis of water in suspension with n-Zr, the yield of hydrogen increases by 5.4 times compared to the processes of radiolysis in an adsorbed state. However, in radiation-heterogeneous processes of obtaining hydrogen from water in contact with metal systems, it is necessary to take into account that as a result of these processes surface oxidation occurs and after a certain time the systems are converted to n-Me-MeO+H2Oliq. systems. For nano sized oxide compounds, the mean free path of secondary electrons formed as a result of primary processes of interaction of quanta with atoms is commensurate with the particle sizes of nano-oxides (λ ≈ R_(H-оxides)). Further, these electrons interact with the electronic subsystem of silicon. For nanocatalysts, the length of free paths of secondary and subsequent generations of electrons is greater than the size of catalyst particles (R_cat≤100nm). Usually, their energy is sufficient to conduct independent radiolytic processes in the contact medium of the catalyst.

HLA class I (HLA-I) allotypes vary widely in their dependence on tapasin (TAPBP), an integral component of the peptide-loading complex, to present peptides on the cell surface. We identified two single-nucleotide polymorphisms that regulate TAPBP messenger RNA (mRNA) expression in Africans, rs111686073 (G/C) and rs59097151 (A/G), located in an AP-2α transcription factor binding site and a microRNA (miR)-4486 binding site, respectively. rs111686073G and rs59097151A induced significantly higher TAPBP mRNA expression relative to the alternative alleles due to higher affinity for AP-2α and abrogation of miR-4486 binding, respectively. These variants associated with lower Plasmodium falciparum parasite prevalence and lower incidence of clinical malaria specifically among individuals carrying tapasin-dependent HLA-I allotypes, presumably by augmenting peptide loading, whereas tapasin-independent allotypes associated with relative protection, regardless of imputed TAPBP mRNA expression levels. Thus, an attenuated course of malaria may occur through enhanced breadth and/or magnitude of antigen presentation, an important consideration when evaluating vaccine efficacy.

Among the widespread trichothecene mycotoxins, T-2 toxin is considered the most toxic congener. In the present study, we utilized high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), coupled to the zebrafish (Danio rerio) embryo model, as a toxicometabolomics approach to elucidate the cellular, molecular and biochemical pathways associated with T-2 toxicity. Aligned with previous studies in the zebrafish embryo model, exposure to T-2 toxin was lethal in the high parts-per-billion (ppb) range, with a median lethal concentration (LC50) of 105 ppb. Exposure to the toxins was, furthermore, associated with system-specific alterations in the production of reactive oxygen species (ROS), including decreased ROS production in the liver and increased ROS in the brain region, in the exposed embryos. Moreover, metabolic profiling based on HRMAS NMR revealed the modulation of numerous, interrelated metabolites, specifically including those associated with (1) phase I and II detoxification, and antioxidant pathways; (2) disruption of the phosphocholine lipids of cell membranes; (3) mitochondrial energy metabolism, including apparent disruption of the tricarboxylic acid (TCA) cycle, and the electron transport chain of oxidative phosphorylation, as well as “upstream” effects on carbohydrate, i.e., glucose metabolism; and (4) several compensatory catabolic pathways. Taken together, these observations enabled development of an integrated, system-level model of T-2 toxicity in relation to human and animal health.

Polyethylene terephthalate (PET) is one of the most produced plastic materials in the world. The emergence of microplastics and nanoplastics (MPs/NPs) as a significant environmental contaminant has become a matter of increasing concern. While the toxicological effects of PET NPs have been widely researched, there is a lack of methodologies for studying their accumulation. The present study introduces a novel method to monitor the distribution of PET NPs in germinating wheat (Triticum aestivum L.) seeds. This involves the functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with PET NPs (PET–fSPIONs) coupled with magnetic resonance microimaging (µMRI) to provide insight into their distribution within the seed. The present study has demonstrated that PET–fSPIONs accumulate in specific regions of germinating wheat seeds, including the shoot apical meristem, the radicle, the coleoptile, the plumule, and the scutellum. Furthermore, the accumulation of PET–fSPIONs has been shown to exert a discernible effect on spin–spin relaxation (T2), as observed via MRI and quantitative T2 relaxation time analysis. The accumulation of PET NPs in embryo regions was also confirmed by SEM. Diffusion-weighted magnetic resonance imaging (DW-MRI) and non-invasive chemical shift imaging analyses demonstrated that PET NPs resulted in restricted diffusion within the highlighted areas, as well as an impact on lipid content. Our study reveals that using µMRI with fSPIONs provides a non-invasive method to monitor the biodistribution of PET nanoparticles in wheat seeds. Additionally, it offers valuable insights into the microstructural interactions of PET.

CD8+ T cells are key mediators of antiviral and antitumor immunity. The isolation and study of Ag-specific CD8+ T cells, as well as mapping of their MHC restriction, has practical importance to the study of disease and the development of therapeutics. Unfortunately, most experimental approaches are cumbersome, owing to the highly variable and donor-specific nature of MHC-bound peptide/TCR interactions. Here we present a novel system for rapid identification and characterization of Ag-specific CD8+ T cells, particularly well suited for samples with limited primary cells. Cells are stimulated ex vivo with Ag of interest, followed by live cell sorting based on surface-trapped TNF-α. We take advantage of major advances in single-cell sequencing to generate full-length sequence data from the paired TCR α- and β-chains from these Ag-specific cells. The paired TCR chains are cloned into retroviral vectors and used to transduce donor CD8+ T cells. These TCR transductants provide a virtually unlimited experimental reagent, which can be used for further characterization, such as minimal epitope mapping or identification of MHC restriction, without depleting primary cells. We validated this system using CMV-specific CD8+ T cells from rhesus macaques, characterizing an immunodominant Mamu-A1*002:01-restricted epitope. We further demonstrated the utility of this system by mapping a novel HLA-A*68:02-restricted HIV Gag epitope from an HIV-infected donor. Collectively, these data validate a new strategy to rapidly identify novel Ags and characterize Ag-specific CD8+ T cells, with applications ranging from the study of infectious disease to immunotherapeutics and precision medicine.

ABSTRACT: Introduction. Approximately 20% of accidents in buildings and structures are associated with the destruction of metal structures. Nanocoatings applied to metal structures significantly improve their operational properties, but at the same time make it difficult to use traditional non-destructive testing methods that require access to the surface of the base metal. The quality of the nanocoating is controlled during its formation. To prevent the destruction of metal structures, it is necessary to identify structural heterogeneities of the base metal in micro- and sub-micron sizes, which arise in areas of increased mechanical stress concentration and transform into macrodefects leading to structural failure. Methods and tools are required to non-destructively identify the stress-strain state and damage of the base metal structure through the layer of nanocoating. Electromagnetic-acoustical (EMA) transformation, is considered promising for solving this problem. Existing EMA tools do not fully utilize the potential of EMA conversion, have insufficient sensitivity and the lack of informativity. Methods and materials. For experimental research, we selected widely used in construction structures steels. Research was conducted on the interrelationship of structural alterations in standard samples of metals and the parameters of the electro-magnetic (EMA) transducer under static and cyclic loads. Results. Load diagrams of metal samples were obtained, with accompanying photographs of microstructure in control points, along with their frequency models derived through spectral analysis of the signal from EMA transducer. Discussion. Changes in the stress-strain state of the metal and accumulation of damage in its structure result in a complex interrelated set of changes in mechanical, acoustic, and electro-physical properties, all of which are reflected in the changes in the parameters of the frequency model. Conclusion. Based on the results of the conducted research, the use of a frequency model has been proposed as an integral parameter for identifying the stress-strain state and damage of metal in the equipment. The use of an artificial neural network for analyzing frequency model parameters simplifies the process of identifying the stress-strain state and damage of metal structures and increases its reliability.

ABSTRACTMatrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) could aid the diagnosis of acute respiratory infections (ARIs) owing to its affordability and high-throughput capacity. MALDI-TOF MS has been proposed for use on commonly available respiratory samples, without specialized sample preparation, making this technology especially attractive for implementation in low-resource regions. Here, we assessed the utility of MALDI-TOF MS in differentiating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vs non-COVID acute respiratory infections (NCARIs) in a clinical lab setting in Kazakhstan. Nasopharyngeal swabs were collected from inpatients and outpatients with respiratory symptoms and from asymptomatic controls (ACs) in 2020–2022. PCR was used to differentiate SARS-CoV-2+ and NCARI cases. MALDI-TOF MS spectra were obtained for a total of 252 samples (115 SARS-CoV-2+, 98 NCARIs, and 39 ACs) without specialized sample preparation. In our first sub-analysis, we followed a published protocol for peak preprocessing and machine learning (ML), trained on publicly available spectra from South American SARS-CoV-2+ and NCARI samples. In our second sub-analysis, we trained ML models on a peak intensity matrix representative of both South American (SA) and Kazakhstan (Kaz) samples. Applying the established MALDI-TOF MS pipeline “as is” resulted in a high detection rate for SARS-CoV-2+ samples (91.0%), but low accuracy for NCARIs (48.0%) and ACs (67.0%) by the top-performing random forest model. After re-training of the ML algorithms on the SA-Kaz peak intensity matrix, the accuracy of detection by the top-performing support vector machine with radial basis function kernel model was at 88.0%, 95.0%, and 78% for the Kazakhstan SARS-CoV-2+, NCARI, and AC subjects, respectively, with a SARS-CoV-2 vs rest receiver operating characteristic area under the curve of 0.983 [0.958, 0.987]; a high differentiation accuracy was maintained for the South American SARS-CoV-2 and NCARIs. MALDI-TOF MS/ML is a feasible approach for the differentiation of ARI without specialized sample preparation. The implementation of MALDI-TOF MS/ML in a real clinical lab setting will necessitate continuous optimization to keep up with the rapidly evolving landscape of ARI.IMPORTANCEIn this proof-of-concept study, the authors used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and machine learning (ML) to identify and distinguish acute respiratory infections (ARI) caused by SARS-CoV-2 versus other pathogens in low-resource clinical settings, without the need for specialized sample preparation. The ML models were trained on a varied collection of MALDI-TOF MS spectra from studies conducted in Kazakhstan and South America. Initially, the MALDI-TOF MS/ML pipeline, trained exclusively on South American samples, exhibited diminished effectiveness in recognizing non-SARS-CoV-2 infections from Kazakhstan. Incorporation of spectral signatures from Kazakhstan substantially increased the accuracy of detection. These results underscore the potential of employing MALDI-TOF MS/ML in resource-constrained settings to augment current approaches for detecting and differentiating ARI.

The purpose of this work is to determine the quality of wheat dough with the addition of rice flour-a by-product in the production of cereals. The study revealed a pattern of changes in the physical and chemical properties of wheat dough with the addition of rice flour. Based on the results of the study, it can be concluded that the use of the EKA-1000 improver increases the amount of rice flour introduced (15 % to the total weight of wheat flour) in the recipe, which reduces the cost of the finished product and increases the nutritional value of 1st grade wheat flour, which improves test quality.

Background. According to some studies, nutrient deficiencies reach an over-70% prevalence in ovarian cancer, among other gynaecological malignancies, thus constituting an important risk factor for postoperative mortality, surgical complications and longer hospital stays. Therefore, effective nutrient deficiency correction methods are warranted to improve the ovarian cancer outcomes, especially in patients following radical surgical interventions. New systematic evidence emerges in literature on the impact of such novel methods on the critical status of variant-category patients. Meanwhile, such evidence bears a recommendatory value only, with no current standard or protocol assumed for nutrient deficiency management. This issue presently remains open and requires careful research and analysis.Materials and methods. The clinical case demonstrates the efficacy of nutrient deficiency correction in an ovarian cancer patient following an individualised radical surgery.Results and discussion. The energy supplied on day 1 was >42%, >83% on day 3, and the target values had been achieved by day 7 of intensive therapy. The nutrient deficiency marker dynamics revealed the growth of transferrin, triglycerides and peripheral blood lymphocyte counts as early as by day 3 post-surgery. Albumin was the latest to respond, increasing only on day 7.Conclusion. The introduction of novel nutrition strategies and knowledge of their impact depend on further high-quality research, especially prospective studies, incorporating a greater homogeneity of intervention types and clinical outcomes, as well as wider sampling of female ovarian cancer.

The current state of the use of methods of stopping wagons on railway transport in cases of their spontaneous departure is investigated. As a result, it was found that cases of spontaneous departure of rolling stock on railways in the region of the Republic of Uzbekistan account for 4.2% of the total share of traffic safety violations and account for 19.9% of the damage caused. This article highlights that in order to prevent the above situations, after installing brake shoes through automatic braking, a device on a spontaneously departing rolling stock, taking into account the number of wagons and their state of loading, based on the development of a mathematical model for determining the stopping distance, a system operating without a human factor was created and introduced into production.

The implementation of Russia’s energy strategy provides for the creation of an intelligent control system for active-adaptive electrical networks of the electric power complex, which contains a system for remote diagnostic monitoring of energy equipment, including metal load-bearing structures of electrical energy generation, transmission and consumption facilities. Promising in this regard is the use of a high-performance electromagnetic-acoustic method, which allows non-contact detection of metal defects and monitoring of their stress-strain state. But existing electromagnetic-acoustic diagnostic tools do not have sufficient sensitivity and information content to solve this problem. The article presents the results of experimental studies aimed at identifying and processing informative parameters of electromagnetic-acoustic transformation for the implementation of remote diagnostic monitoring of the stress-strain state and metal damage of power equipment. Based on the research results, it was proposed to use a frequency model formed as a result of spectral analysis of the electromagnetic-acoustic transducer signal as an integral parameter characterizing the state of the metal.

In the oil and gas industry, to assess the technical condition of equipment, diagnostic methods and tools are used aimed at identifying defects that are unacceptable, according to regulatory documents. In places where mechanical stress is concentrated, microdefects in the metal structure arise, which, under the influence of static and dynamic loads, develop into macrodefects that cause equipment destruction. To identify areas of concentration of mechanical stress and localize metal microdamages, it is proposed to use a non-contact, high-performance electromagnetic-acoustic diagnostic method. But existing electromagnetic-acoustic diagnostic tools lack sensitivity and information content. The article provides an analysis of the influence of the stress-strain state of the metal on the parameters of electromagnetic-acoustic transformation in order to identify additional informative parameters and methods for their processing to solve the problem of identifying the stress-strain state and damage to the metal structure of oil and gas equipment.

Research aimed at the design and development of artificial intelligence systems is currently in great demand. These systems have gained particular popularity when integrated into complex multi-level technical complexes, which include energy industry facilities. The introduction of modern information processes for the rapid processing of technical information makes it possible to develop and implement expert systems for developing generative management decisions using an artificial intelligence system. Such modern approaches in the field of digitalization and information processing, such as the creation of digital twins of physical objects, allow for research and qualitative assessment of management decisions when implementing expert systems.

See the retraction notice E3S Web of Conferences 549, 00001 (2024), https://doi.org/10.1051/e3sconf/202454900001

Abstract Ochratoxin A (OTA) is one of the most widespread mycotoxin contaminants of agricultural crops. Despite being associated with a range of adverse health effects, a comprehensive systems-level mechanistic understanding of the toxicity of OTA remains elusive. In the present study, metabolic profiling by high-resolution magic angle spinning (HRMAS) NMR, coupled to intact zebrafish embryos, was employed to identify metabolic pathways in relation to a systems-level model of OTA toxicity. Embryotoxicity was observed at sub-micromolar exposure concentrations of OTA. Localization of OTA, based on intrinsic fluorescence, as well as a co-localization of increased reactive oxygen species production, was observed in the liver kidney, brain and intestine of embryos. Moreover, HRMAS NMR showed significant alteration of metabolites related to targeting of the liver (i.e., hepatotoxicity), and pathways associated with detoxification and oxidative stress, and mitochondrial energy metabolism. Based on metabolic profiles, and complementary assays, an integrated model of OTA toxicity is, thus, proposed. Our model suggests that OTA hepatotoxicity compromises detoxification and antioxidant pathways, leading to mitochondrial membrane dysfunction manifested by crosstalk between pathways of energy metabolism. Interestingly, our data additionally aligns with a possible role of mitochondrial fusion as a “passive mechanism” to rescue mitochondrial integrity during OTA toxicity.

The article substantiates the choice of materials for designing adaptive underclothes for the most severe group of children with infantile cerebral paralysis – bed patients. As a rule, these are denied children, who, in principle, spend their lives in medical hospitals, require constant care by medical staff. Such children are in sharp need of specialized adaptive underclothes, which could significantly improve the quality of life of such children and facilitate care for them by medical staff. In many respects the quality of similar clothes depends on properly selected materials. Analysis of modern innovative materials that could have been used to create such clothes was conducted. Hygienic, physical and mechanical properties of existing knitted materials were studied according to standard methods for identifying the most suitable for similar clothes.

Endometriosis is a chronic and debilitating disease with chronic pelvic pain and infertility. This pathology affects 1 in 10 women worldwide. Chronic pelvic pain is the main complaint of patients with endometriosis, which causes the most discomfort and has a strong impact on the quality of life. Today, the main generally accepted criterion for the severity of pain is the volume of the affected tissue, but most often it does not correspond to the real pain sensations of the patients. In this review of the literature, we have identified and compared the main pathophysiological mechanisms of the development of pain in endometriosis, which help to answer some urgent questions. We have identified 6 mechanisms that sequentially activate and reinforce each other's action, leading to the formation of persistent pain syndrome. There are still gaps in the pathophysiological mechanisms described by us, which requires additional clinical studies. A better understanding of the pathophysiology of pain in endometriosis will help improve diagnostic capabilities, as well as treatment that will be directed at each link in the pathological process.

The study conducted among medical personnel identified that children with infantile cerebral paralysisof the V severity level need clothes with improved properties that ensure the patient’s quality of life and the correct conduct of medical and hygienic procedures by medical personnel.