Search

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

Abstract Background Computational cell type deconvolution enables the estimation of cell type abundance from bulk tissues and is important for understanding tissue microenviroment, especially in tumor tissues. With rapid development of deconvolution methods, many benchmarking studies have been published aiming for a comprehensive evaluation for these methods. Benchmarking studies rely on cell-type resolved single-cell RNA-seq data to create simulated pseudobulk datasets by adding individual cells-types in controlled proportions. Results In our work, we show that the standard application of this approach, which uses randomly selected single cells, regardless of the intrinsic difference between them, generates synthetic bulk expression values that lack appropriate biological variance. We demonstrate why and how the current bulk simulation pipeline with random cells is unrealistic and propose a heterogeneous simulation strategy as a solution. The heterogeneously simulated bulk samples match up with the variance observed in real bulk datasets and therefore provide concrete benefits for benchmarking in several ways. We demonstrate that conceptual classes of deconvolution methods differ dramatically in their robustness to heterogeneity with reference-free methods performing particularly poorly. For regression-based methods, the heterogeneous simulation provides an explicit framework to disentangle the contributions of reference construction and regression methods to performance. Finally, we perform an extensive benchmark of diverse methods across eight different datasets and find BayesPrism and a hybrid MuSiC/CIBERSORTx approach to be the top performers. Conclusions Our heterogeneous bulk simulation method and the entire benchmarking framework is implemented in a user friendly package https://github.com/humengying0907/deconvBenchmarking and https://doi.org/10.5281/zenodo.8206516 , enabling further developments in deconvolution methods.

Summary: To understand the decision process of genomic sequence-to-function models, explainable AI algorithms determine the importance of each nucleotide in a given input sequence to the model’s predictions and enable discovery of cis-regulatory motifs for gene regulation. The most commonly applied method is in silico saturation mutagenesis (ISM) because its per-nucleotide importance scores can be intuitively understood as the computational counterpart to in vivo saturation mutagenesis experiments. While ISM is highly interpretable, it is computationally challenging to perform for many sequences, and becomes prohibitive as the length of the input sequences and size of the model grows. Here, we use the first-order Taylor approximation to approximate ISM values from the model’s gradient, which reduces its computation cost to a single forward pass for an input sequence. We show that the Taylor ISM (TISM) approximation is robust across different model ablations, random initializations, training parameters, and dataset sizes.

The purpose of the study was to improve the remuneration system for operators of automatic lines, machines and plants by using the labor participation rate, which will allow making optimal management decisions on accounting for payroll settlements with staff and the achieving of strategic goals of the organization. The article suggests the ways to solve the problem using the example of improving the system of awarding bonuses to the staff of a manufacturing enterprise, it is recommended to use formulas that allow evaluating the productivity of an individual employee. Software implementation in the 1C:Enterprise system is performed. The developed software solution allows you to automate the process of calculating bonuses for operators of lines, machines and plants, taking into account the amount of work each employee does. The proposed algorithm for calculating the labor participation coefficient is supposed to be developed in further studies to more accurately assess the contribution of an employee's labor, for example, by taking into account defects and evaluating the quality of manufactured products. Purpose. Development of an algorithm for calculating the coefficient of labor participation of operators of lines, machines and plants using the 1C:Enterprise system. Methodology: in article methods for formalizing and specifying formulas used in calculating the labor participation rate, and also development methods on the 1C:Enterprise platform were used. Results. The software implementation of calculating the premiums of operators of lines, machines and plants taking into account the labor participation coefficient is performed. Practical implications it is expedient to apply the received results the manufacturing enterprises staffed by operators of automatic or semi-automatic lines, machines and plants.

The aim of this paper is the semiotic analysis of a foreign language textbook as a semiotic phenomenon reflecting the cognitive attitudes of its authors and aimed at forming not only external but also deep layers of the learner's linguistic personality, responsible for motivation, intents and attitudes. The material to be analysed is a popular line of EFL textbooks “English file” by British authors Ch. Latham-Koenig and C. Oxenden. The scientific novelty of the work is that for the first time a foreign language textbook is considered not as an educational and methodological text, but as an alternative reality, a dynamic complex sign, similar to the discursive space of a fiction book. The study is conducted by applying the method of contextual analysis, the method of cognitive-pragmatic analysis, and the interpretive method to the polycoded texts of EF-textbooks. The authors conclude that the semiotic complex of EF-textbooks exhibits the characteristics of an educational novel of fiction, where the learner assumes the function of a fairy-tale hero, acting in the space of English-language cultural mythologems, reference-metric elements, topoi and narratives. As a result of active realisation of the happy end narrative, supported by the system of topoi and precedent names characteristic of the English-language conceptosphere, the textbook uses the suggestive potential of the so-called soft power to form changes at the motivational-pragmatic level of the linguistic personality.

Background. Diagnosis of hypersensitivity pneumonitis (HP) using high-resolution computed tomography (HRCT) is not an easy task. The most difficult aspects of the disease include differential diagnosis of its fibrotic (fHP) and non-fibrotic (nfHP) phenotypes, as well as their differentiation from usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis. The determination of fibrous changes at an early stage of development can significantly accelerate the beginning of antifibrotic therapy and improve the prognosis.Objective: to identify key HRCT signs for reliable differentiation of fHP and nfHP, to carry out differential diagnostics between fHP and UIP.Material and methods. The data of 73 patients with morphologically verified HP, in whom HRCT had been performed, were retrospectively analysed. In 21 patients, nfHP was determined, and in 52 patients fHP was identified. The comparison group consisted of 24 patients with a typical radiological UIP pattern. The analysis of the changes detected during HRCT was carried out by qualitative and semi-quantitative methods. The significance of qualitative differences in a sign manifestation was assessed by Fisher’s exact test, semi-quantitative differences were evaluated using Mann–Whitney test.Results. The results of the study allow to assume, that the presence and degree of manifestation of certain HRCT signs significantly differ between the selected groups of patients in qualitative and/or semi-quantitative terms. In cases of НP, the distribution of changes was mostly uniform and diffuse, with no clear predominance in certain lobes. In UIP, diffuse craniocaudal distribution took place, and in the axial plane, the changes were mainly subpleural in nature.Conclusion. Based on the results of the study, it can be assumed that fHP significantly differs from nfHP in such features as the presence and degree of manifestation of ground glass and honeycombing symptoms, reticular changes and traction bronchiectases. When comparing the fHP and UIP groups, the distinctive signs of fHP were centrilobular nodules, mosaic pattern, as well as diffuse axial sign distribution.

Quantum phases can be classified by topological invariants, which take on discrete values capturing global information about the quantum state1-13. Over the past decades, these invariants have come to play a central role in describing matter, providing the foundation for understanding superfluids5, magnets6,7, the quantum Hall effect3,8, topological insulators9,10, Weyl semimetals11-13 and other phenomena. Here we report an unusual linking-number (knot theory) invariant associated with loops of electronic band crossings in a mirror-symmetric ferromagnet14-20. Using state-of-the-art spectroscopic methods, we directly observe three intertwined degeneracy loops in the material's three-torus, T3, bulk Brillouin zone. We find that each loop links each other loop twice. Through systematic spectroscopic investigation of this linked-loop quantum state, we explicitly draw its link diagram and conclude, in analogy with knot theory, that it exhibits the linking number (2, 2, 2), providing a direct determination of the invariant structure from the experimental data. We further predict and observe, on the surface of our samples, Seifert boundary states protected by the bulk linked loops, suggestive of a remarkable Seifert bulk-boundary correspondence. Our observation of a quantum loop link motivates the application of knot theory to the exploration of magnetic and superconducting quantum matter.

Co-functional proteins tend to have rates of evolution that covary over time. This correlation between evolutionary rates can be measured over the branches of a phylogenetic tree through methods such as evolutionary rate covariation (ERC), and then used to construct gene networks by the identification of proteins with functional interactions. The cause of this correlation has been hypothesized to result from both compensatory coevolution at physical interfaces and nonphysical forces such as shared changes in selective pressure. This study explores whether coevolution due to compensatory mutations has a measurable effect on the ERC signal. We examined the difference in ERC signal between physically interacting protein domains within complexes compared to domains of the same proteins that do not physically interact. We found no generalizable relationship between physical interaction and high ERC, although a few complexes ranked physical interactions higher than nonphysical interactions. Therefore, we conclude that coevolution due to physical interaction is weak, but present in the signal captured by ERC, and we hypothesize that the stronger signal instead comes from selective pressures on the protein as a whole and maintenance of the general function.

A recent randomized trial evaluated the impact of mask promotion on COVID-19-related outcomes. We find that staff behavior in both unblinded and supposedly blinded steps caused large and statistically significant imbalances in population sizes. These denominator differences constitute the rate differences observed in the trial, complicating inferences of causality.

The authors of numerous measurements of conductivity for suspensions of nanoparticles of various types carried out in the last decade came to the general conclusion that the well-known Maxwell’s theory is not applicable to quantitative explanation of the properties of such systems. In the present work, we demonstrate that the Maxwell’s theory can be still applicable even for such systems, but the specifics of the standard ac measurements have to be correctly taken into account. Namely, the dependence of the capacitance of “metal–electrolyte” cuvette boundaries on nanoparticle adsorption, which in its turn dramatically depends on nanoparticle concentration, has to be taken into account. The latter circumstance strongly (via the RC characteristic of the circuit) affects the results of conductivity measurements. We propose the new algorithm of the impedance measurement data analysis for the particles’ concentration dependence of conductivity σ(ϕ) (where ϕ is the volume fraction of nanoparticles in suspension) for the suspensions of the diamante nanoparticles in alcohol which demonstrates the adequate correspondence of the Maxwell’s theory to the available experimental findings.

BACKGROUND: Patients with gout often take glucocorticoids (GCs) and are at high risk of developing type 2 diabetes mellitus (DM2).AIM: Evaluation of the effect of long-term use of low doses of GCs on the risk of developing DM in patients with gout based on the results of a retrospective observationMATERIALS AND METHODS: 317 out of 444 patients with gout and no DM2 who participated in a prospective study of risk factors for DM2 were included. The sample did not include patients who used GCs during the observation period to relieve an acute attack of arthritis, regardless of the method of their use (n=88) and who did not complete the study (n=39). The remaining patients were retrospectively divided into 2 groups: those who continuously took prednisolone at a dose of 5-10 mg/day for ≥180 days and did not use GCs during the observation period. Scheduled visits were carried out at least once every 2 years. During the 1st visit, patients were prescribed or corrected both urate-lowering and prophylactic antiinflammatory therapy, including low doses of GCs. The primary end point was the development of DM2, carbohydrate metabolism indicators (HbA1c levels, serum glucose levels) were compared at baseline and at the end of the study.RESULTS: Of 317 patients with gout, 76 patients (24%) were continuously taking prednisolone at a dose of 5-10 mg/day for ≥180 days, 241 patients (76%) did not receive GCs during the entire follow-up period. The average dose of prednisolone in patients of the main group was 7.9±1.2 mg/day, the duration of treatment was 206.3±20.4 days.DM2 developed during the observation period in 20% of the main group and in 22% of the comparison group (p=0.73). Patients who took GC were older than those who did not take GC (p=0.01), they were more likely to have CHF (p=0.04). There were no significant differences between the groups for the rest of the compared parameters. In patients treated with low doses of GC — a significant increase in the average level of HbA1c (p=0.002); an increase in the number of patients with glucose levels ≥6.1 mmol/l (p=0.004) by the end of the study relative to the baseline. The initial level of HbA1c in patients who developed DM2 was expectedly higher, among them smokers were more often detected (p=0.01), they had a higher level of serum UA (p=0.001). The prevalence of other risk factors for DM in those who developed and did not develop DM2 did not differ significantly.CONCLUSION: Long-term use of low doses of GC in patients with gout does not significantly increase the risk of developing DM2, but may have a negative effect on carbohydrate metabolism.

Introduction. The article deals with the problem of digital education on the example of natural science disciplines, in particular Mathematics, when training students of Nizhny Novgorod Academy of Russian MIA (Ministry of Internal Affairs) – future specialists in the sphere of ensuring economic security. Purpose of research is to highlight specific features of training students in the conditions of digital educational process at the Nizhny Novgorod Academy of Russian MIA on the example of teaching “Mathematics”. Methods. Analysis and synthesis of psychological, pedagogical and didactic-methodical literature; generalization and systematization; monitoring, interview, pedagogical diagnostics, pedagogical experiment. Research results. This work deals with specific features of digital contemporary vocational education, advantages and disadvantages of educational process when using modern digital technologies. It represents the experience of using elements and resources of distance training system Moodle to deliver classes in natural science disciplines, in particular Mathematics, in order to realize the basic programs of vocational education. Apart from, the specificity of both planning and adoption of e-learning courses in electronic educational environment of higher school is determined in the article; it shows possibilities of how students can master specific knowledge, skills and necessary competences when training disciplines that are taught by teachers of Maths, Computing and Information technologies department and possibilities of further development of successful practice work in the sphere of economic security. Field of applying results. Research results can be the basis for drafting and using e-leaning courses in other disciplines as the tool for realizing digital education in various higher schools. Conclusions. The research work highlights the fact that traditional education in the conditions of digital technologies development is less effective especially if it concerns distance training. In order to improve its efficiency it is necessary to implement digital education elements, in particular the resources of SDE (System of Distance Education) LMS Moodle, to deliver classes in mathematical disciplines. The results of experiment and interviewing of both students and higher school teachers allow to identify both advantages and disadvantages of transformation from traditional to innovative education format. Digitalization has a lot of advantages but in order to get highly-quality education and a set of necessary competences when learning a discipline, it is important to consider both traditional and digital education as a single purposeful process of training and upbringing. The model of digital education is in need of training a highly-qualified specialist that would include in its system substantial aspects of training process; pedagogical methods and technologies; organization and management arrangements; all necessary facilities have to be created; and when training all possible ways of solving upbringing tasks should be highlighted.

The formation of specific cellular protrusions, plasma membrane blebs, underlies the amoeboid mode of cell motility, which is characteristic for free-living amoebae and leukocytes, and can also be adopted by stem and tumor cells to bypass unfavorable migration conditions and thus facilitate their long-distance migration. Not all cells are equally prone to bleb formation. We have previously shown that membrane blebbing can be experimentally induced in a subset of HT1080 fibrosarcoma cells, whereas other cells in the same culture under the same conditions retain non-blebbing mesenchymal morphology. Here we show that this heterogeneity is associated with the distribution of vimentin intermediate filaments (VIFs). Using different approaches to alter the VIF organization, we show that blebbing activity is biased toward cell edges lacking abundant VIFs, whereas the VIF-rich regions of the cell periphery exhibit low blebbing activity. This pattern is observed both in interphase fibroblasts, with and without experimentally induced blebbing, and during mitosis-associated blebbing. Moreover, the downregulation of vimentin expression or displacement of VIFs away from the cell periphery promotes blebbing even in cells resistant to bleb-inducing treatments. Thus, we reveal a new important function of VIFs in cell physiology that involves the regulation of non-apoptotic blebbing essential for amoeboid cell migration and mitosis.