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Abstract The main pathophysiological hallmark of Parkinson's disease (PD) is the accumulation of aggregated alpha‐synuclein (αSyn). Microglial activation is an early event in PD and may play a key role in pathological αSyn aggregation and transmission, as well as in clearance of αSyn and immunotherapy efficacy. Our aim was to investigate how different proposed mechanisms of anti‐αSyn immunotherapy may contribute to pathology reduction in various PD‐like mouse models. Our mechanistic model of PD pathology in mouse includes αSyn production, aggregation, degradation and distribution in neurons, secretion into interstitial fluid, internalization, and subsequent clearance by neurons and microglia. It describes the influence of neuroinflammation on PD pathogenesis and dopaminergic neurodegeneration. Multiple data from mouse PD models were used for calibration and validation. Simulations of anti‐αSyn passive immunotherapy adequately reproduce preclinical data and suggest that (1) immunotherapy is efficient in the reduction of aggregated αSyn in various models of PD‐like pathology; (2) prevention of aSyn spread only does not reduce the pathology; (3) a decrease in microglial inflammatory activation and aSyn aggregation may be alternative therapy approaches in PD‐like pathology.

Abstract Economic costs of climate change are conventionally assessed at the aggregated global and national levels, while adaptation is local. When present, regionalised assessments are confined to direct damages, hindered by both data and models’ limitations. This article goes beyond the aggregated analysis to explore direct and indirect economic consequences of sea level rise (SLR) at regional and sectoral levels in Europe. Using a dynamic computable general equilibrium model and novel datasets, we estimate the distribution of losses and gains across regions and sectors. A comparison of a high-end scenario against a no-climate-impact baseline suggests a GDP loss of 1.26% (€871.8 billion) for the whole EU&UK. Conversely our refined assessments show that some coastal regions lose 9.56–20.84% of GDP, revealing striking regional disparities. Inland regions grow due to the displaced demand from coastal areas, but the GDP gains are small (0–1.13%). While recovery benefits the construction sector, public services and industry face significant downturns. We show that prioritising recovery of critical sectors locally reduces massive regional GDP losses, at negligible costs to the overall European economy. Our analysis traces regional economic restructuring triggered by SLR, underscoring the necessity of region-specific adaptation policies that embrace uneven geographic impacts and unique sectoral profiles to inform resilient strategy design.

Respuesta final de Ivanova a Horno y conclusión del debate.

Uno de los debates centrales en la lingüística actual gira en torno a la consideración de las categorías gramaticales de nombre y verbo como discretas o graduales. En este trabajo, parto de las evidencias sobre la adquisición, el procesamiento y la producción de estas dos clases léxicas en hablantes sanos y hablantes con trastornos para defender que, desde el punto de vista neurocognitivo, se trata de categorías discretas. Además, analizo el tipo de condicionamiento de la disociación categorial con el fin de defender que la procedimentalización de la función lingüística a lo largo de la vida conduce a la generación de la naturaleza gramatical-semántica de las clases léxicas. Para ello, reviso y analizo los resultados de una serie de trabajos experimentales, de naturaleza sobre todo neurofuncional y neurocognitiva, que me permiten comparar la disociación categorial y su disociación causativa en niños, adultos y mayores sanos y con diferentes tipos de trastornos de naturaleza cognitiva (TEL, TEA; afasias; DS y EA). La conclusión principal de mi trabajo es que nombre y verbo son categorías gramaticales discretas en términos neurocognitivos, que desarrollan gradualidad gramatical-semántica con la procedimentalización de la función del lenguaje.

Во второй части статьи анализируются закономерности формирования и развития архитектурно-пространственной среды городов-столиц, возникших на этапе Новейшего времени в период научно-технической революции и ликвидации колониализма: Бразилиа, Чандигарх, Исламабад, Додома, Абуджа, а также в период глобальной цифровизации: Берлин, Астана, Путраджайя. На основе проведённого анализа впервые сформирована таблица – матрица характерных особенностей архитектурно-пространственной среды столиц на различных его уровнях.*

Background and Aim: The main purpose of a national bioresource center is to standardize, centralize, preserve, and ensure accessibility of microbial bioresources that accumulate there because of state research programs. The establishment of national bioresource centers for antibiotic-resistant microorganisms allows to solve practical problems in the field of veterinary service, as well as to develop effective chemotherapeutic and disinfectant drugs to overcome the mechanisms of resistance. This study aimed to outline the process of forming a national culture collection of antibiotic-resistant strains of zoonotic bacteria in the Russian Federation using two microbial strains. Materials and Methods: The object of research was isolates of Salmonella spp., Escherichia coli, Enterococcus spp., Campylobacter spp., Listeria monocytogenes, and Staphylococcus spp., all of which were obtained from biomaterials of farm animals, feed samples, bedding, water from livestock buildings, washouts from environmental objects, and food products. The resistance of bacterial isolates was determined using microbiological and molecular-genetic research methods. Results: During monitoring studies, 1489 bacterial isolates were isolated. In total, 408 bacterial isolates were tested for sensitivity to antimicrobial agents, including E. coli (47.6%), Salmonella spp. (30.4%), Enterococcus spp. (11.3%), and Campylobacter spp. (10.8%). For genetic characterization, 95 isolates of Salmonella enterica, E. coli, Campylobacter spp., L. monocytogenes, Staphylococcus spp., Enterococcus spp. were chosen from the research collection, which was formed as part of the monitoring program for antibiotic resistance. Conclusion: Deposited isolates that underwent whole-genome analysis can be used as positive control samples both in the development and use of methods or test systems for the detection of various resistance genes in zoonotic bacteria. In addition, such isolates can also be used for microbiological studies related to determining the sensitivity of microorganisms to antibacterial drugs, for phenotypic studies in the diagnosis of various bacterial infections in animals and birds, and retrospective analysis of strains from numerous collections.

Abstract Age-related cognitive impairment have increased dramatically in recent years, which has risen the interes in developing screening tools for mild cognitive impairment and Alzheimer's disease. Speech analysis allows to exploit the behavioral consequences of cognitive deficits on the patient's vocal performance so that it is possible to identify pathologies affecting speech production such as dementia. Previous studies have further shown that the speech task used determines how the speech parameters are altered. We aim to combine the impairments in several speech production tasks in order to improve the accuracy of screening through speech analysis. The sample consists of 72 participants divided into three equal groups of healthy older adults, people with mild cognitive impairment, or Alzheimer's disease, matched by age and education. A complete neuropsychological assessment and two voice recordings were performed. The tasks required the participants to read a text, and complete a sentence with semantic information. A stepwise linear discriminant analysis was performed to select speech parameters with discriminative power. The discriminative functions obtained an accuracy of 83.3% in simultaneous classifications of several levels of cognitive impairment. It would therefore be a promising screening tool for dementia.

La alteración de la competencia pragmática forma parte de la sintomatología primaria de numerosos cuadros clínicos vinculados al neurodesarrollo (p. ej., el trastorno del espectro autista), trastornos sobrevenidos (p. ej., lesiones de hemisferio derecho) o enfermedades neurodegenerativas (p. ej., demencia frontotemporal). Asimismo, no es poco común registrar su deterioro secundario, derivado de las alteraciones de otros niveles lingüísticos, como el léxico-semántico (p. ej., enfermedad de Alzheimer). El estudio de tal alteración se enfrenta, no obstante, a una serie de retos de corte teórico (qué se entiende por las unidades de análisis pragmático) y metodológico (cómo estudiar tales unidades y evaluar su grado de afectación). El objetivo de este trabajo es ofrecer una perspectiva crítica sobre los principales desafíos del estudio de la competencia pragmática en enfermedades neurodegenerativas, en particular, la enfermedad de Alzheimer, focalizándose en tres: la variabilidad de posturas teóricas, la variabilidad de enfoques metodológicos, y el papel enmascarador de las estrategias compensatorias.

татья представлена в двух частях: в первой части раскрывается определяющая роль образа города-столицы в контексте формирования государственной и национальной идентичности, определяется связь понятий национальной и архитектурной идентичности; обосновывается целесообразность использования семантических подходов к анализу образа архитектурно-пространственной среды городов-столиц. Далее выявляются и рассматриваются особенности и закономерности формирования архитектурно-пространственной среды городов, получивших статус столицы (новые столицы) в период с начала XIX века по сегодняшний день. Приводятся примеры характерных моделей архитектурно-пространственной среды столиц, сформировавшихся на этапе Нового времени в период становления индустриального общества: Вашингтон, Канберра, Дели.

PCR is the most effective method for detecting difficult-to-cultivate pathogens and pathogens that are part of mixed infections in animals, such as Ornithobacterium rhinotracheale, which causes bird ornithobacteriosis, or Avibacterium paragallinarum, which causes infectious coryza. In this work, we developed and validated two efficient and sensitive diagnostic assays for the rapid and accurate detection of A. paragallinarum and O. rhinotracheale DNA in bacterial isolates and clinical samples using real-time PCR with TaqMan-like probes. When designing the PCR assays, we performed in silico analysis, optimized DNA isolation methods and PCR conditions, and assessed the analytical and diagnostic performance of PCR. We designed primers and probes that have no mismatches with published whole-genome sequences of bacteria. The optimization of conditions showed that the PCR assays are sufficiently robust to changes in temperature and oligonucleotide concentration. The validation showed that the developed assays have high analytical and diagnostic sensitivity and specificity. These assays are expected to improve the differential diagnosis of respiratory diseases in chickens and turkeys.

Abstract Signal transduction governs cellular behavior, and its dysregulation often leads to human disease. To understand this process, we can use network models based on prior knowledge, where nodes represent biomolecules, usually proteins, and edges indicate interactions between them. Several computational methods combine untargeted omics data with prior knowledge to estimate the state of signaling networks in specific biological scenarios. Here, we review, compare, and classify recent network approaches according to their characteristics in terms of input omics data, prior knowledge and underlying methodologies. We highlight existing challenges in the field, such as the general lack of ground truth and the limitations of prior knowledge. We also point out new omics developments that may have a profound impact, such as single‐cell proteomics or large‐scale profiling of protein conformational changes. We provide both an introduction for interested users seeking strategies to study cell signaling on a large scale and an update for seasoned modelers.

The authors of the paper focus on the opportunities that translation activity opens up in the development and preservation of the languages of Russia, reviving the interest in the study and use of native languages in professional activities, including translation. The significance of translation activity as one of the most effective tools for the preservation of languages is substantiated. A concept of the periodization of the history of national translation in Russia is offered. The researchers have reviewed the literatures of the peoples of Russia and studied literary translation as a form of intercultural communication. New ideas on the formation of specific theories of translation using the languages of the peoples of Russia have been introduced. An attempt is made to provide a comprehensive definition of the term "translation with the languages of the peoples of Russia" along with the formation of a system of its basic categories. A model of specific theories of translation using the languages of the peoples of Russia is presented, and the principles of its variability are determined depending on the pairs of contacting languages. The prospects for the development of areas of translation activity using the languages of the peoples of Russia have been outlined, and a concept of translators' training with the languages of the peoples of Russia has been presented. Some aspects of the current state of translation in Tatarstan have been characterized.

The degradation of polylactide (PLA) films of different structures under conditions of controlled composting has been studied. We have demonstrated that PLA underwent degradation within one month in a substrate that simulated standard industrial composting. Regardless of the initial structure of the samples, the number-average molecular weight (Mn) decreased to 4 kDa while the degree of crystallinity increased to about 70% after 21 days of composting. Addition of an inoculant to the standard substrate resulted in the accelerated degradation of the PLA samples for one week due to an abiotic hydrolysis. These findings have confirmed that industrial composting could solve the problem of plastic disposal at least for PLA.

The requirements of the rules and regulations of the Classification Societies are based on the assumption that during the construction and operation of ships the hull corrosion protection measures are implemented according to the standards and other regulatory documents currently in force. For the purposes of designing the ship hull structures, the load components for different corrosion protection types have been obtained in the paper. There have been collected the data on the relationship between the corrosion protection weight load and the ship displacement, which enables to select the lowest corrosion protection type by weight. Technical and economic parameters of corrosion protection of ship hull structures have been analyzed. To achieve the objective of the paper a cumulative simplified approach of economic feasibility of selecting the corrosion protection type for ship hull structures has been employed. It has been determined that a total cost of protection from stress-corrosion fractures decreases for the ships with a displacement of more than 6000 [t] in the case of usage of the impressed current cathodic protection instead of the sacrificial anode cathodic one. The results of the investigation can be used by shipbuilders at the ship design stage, which enables to make a correct selection of a corrosion protection type and decreases its total cost.

The recent pandemic has revealed the urgent need for lung disease diagnosis at early stages in humans. Deep learning-based automatic diagnosis methods typically rely on single-modality data such as medical imaging. However, analysis of single modality data is not so reliable to diagnose the disease at its early stages. Clinical data, blood tests together with imaging methods are very powerful and reliable sources to detect the presence of disease in the human body. This study attempts to use medical imaging data with clinical information to develop a multimodal fusion approach to detect lung disease. Two architectures of multimodal network based on late and intermediate fusion is proposed. Besides, an approach of adapting batch size is also introduced. Experiments show that the performance of intermediate fusion is better than the late fusion model with both direct and adaptive batch size approach.

This paper primarily focuses on the family language policy of bilingual Russian-Estonian and Russian-Spanish families in relation to the maintenance of Russian as a heritage language. Its main objective is to identify social factors that either help or hinder this process. In doing so, this paper searches for commonalities and specificities of the mainstream attitudes towards Russian as a heritage language in Estonia and Spain, by analysing the sociolinguistic situation of Russian in both countries and by examining the factors conditioning the maintenance of Russian as a heritage language in family settings. Our research is based on an in-depth analysis of a variety of sources, mainly quantitative statistical and demographic data on self-reported language behaviour and language ideologies in mixed families from Estonia (n = 40) and Spain (n = 40). The main results of our comparative study confirm the general positive attitude towards Russian as a heritage language, but they also highlight an important variability of these attitudes both between countries and within each community. We show that these attitudes directly determine the principles of family language policy, the parents strategies to transmit Russian as a heritage language, and the level of proficiency in Russian as a heritage language in the second generation. These results allow us to conclude that, as a heritage language, Russian relies on strong attitudinal support in even small communities, like Estonian or Spanish, but also that its confident transmission should rely on external subsidy.

In our introductory article, we outline the main sociolinguistic features of Russian as a heritage language of post-Soviet immigrants in European settings and beyond. We offer a general overview of the evolution of Russian as a global language, with a particular focus on its geodemographics and economic and social value as a lingua franca . Based on this, we analyse the main principles defining the maintenance of Russian as a language of migration and as a heritage language in different countries, and emphasise the most important questions that still need to be addressed in this field of research. The main objective of this special issue is to combine the most recent research on the vitality of different languages of post-Soviet republics in new political milieu, with a particular focus on European and Asian countries, but there are other objectives as well. We propose to explore the factors that have either favoured or hindered the maintenance and transmission of languages of post-Soviet immigrants and repatriates, and how these sociolinguistic processes become evident in language vitality on both private and public levels. Our special issue primarily addresses the questions of family language policy, new language contacts and their management, and linguistic landscape in heritage speakers, diasporas and their new settings in Europe, Asia and the US.

Abstract Molecular knowledge of biological processes is a cornerstone in omics data analysis. Applied to single‐cell data, such analyses provide mechanistic insights into individual cells and their interactions. However, knowledge of intercellular communication is scarce, scattered across resources, and not linked to intracellular processes. To address this gap, we combined over 100 resources covering interactions and roles of proteins in inter‐ and intracellular signaling, as well as transcriptional and post‐transcriptional regulation. We added protein complex information and annotations on function, localization, and role in diseases for each protein. The resource is available for human, and via homology translation for mouse and rat. The data are accessible via OmniPath’s web service ( https://omnipathdb.org/ ), a Cytoscape plug‐in, and packages in R/Bioconductor and Python, providing access options for computational and experimental scientists. We created workflows with tutorials to facilitate the analysis of cell–cell interactions and affected downstream intracellular signaling processes. OmniPath provides a single access point to knowledge spanning intra‐ and intercellular processes for data analysis, as we demonstrate in applications studying SARS‐CoV‐2 infection and ulcerative colitis.

At the places of harvesting coniferous trees and industrial nuts processing remains, a devastating amount of wastes litters large areas of land, poisons the air and the hydro-environment by the combustion products and toxic compounds released during decomposition. Therefore, the search for solution for the effective use of waste is an actual task. The aim of this research is to investigate the influence of fodder additive made of forest waste resources and the enzymes on milk productivity of cows. The experiment has been held on black-and-white breed in Krasnoyarsk region. The experimental group received, in addition to the main diet, some fodder additives consisted of coniferous flower, crushed pine nut shells, arabinogalactane and amilosubtiline HCl enzyme. The analysis of coniferous flower demonstrated that it contains more copper by 41.6%, zinc-55.6%, magnesium-183.3%, chromium-66.7% than in pine nut shell thus, on the contrary, the content of lignin, cellulose and moisture, was more in the shell of pine nuts-24.2%, 9.7% and 5.0%, respectively. Under the effect of the test additives in cows of the experimental group milk yield was higher than the control group, 9.9% (P

The SARS-CoV-2 betacoronavirus pandemic has claimed more than 6.5 million lives and, despite the development and use of COVID-19 vaccines, remains a major global public health problem. The development of specific drugs for the treatment of this disease remains a very urgent task. In the context of a repurposing strategy, we previously screened a library of nucleoside analogs showing different types of biological activity against the SARS-CoV-2 virus. The screening revealed compounds capable of inhibiting the reproduction of SARS-CoV-2 with EC50 values in the range of 20–50 µM. Here we present the design and synthesis of various analogs of the leader compounds, the evaluation of their cytotoxicity and antiviral activity against SARS-CoV-2 in cell cultures, as well as experimental data on RNA-dependent RNA polymerase inhibition. Several compounds have been shown to prevent the interaction between the SARS-CoV-2 RNA-dependent RNA polymerase and the RNA substrate, likely inhibiting virus replication. Three of the synthesized compounds have also been shown to inhibit influenza virus. The structures of these compounds can be used for further optimization in order to develop an antiviral drug.

The article considers the current issues of stimulating innovation in the energy sector and rational use of energy resources. A three-level system of problem-oriented management of human resources for stimulating innovation in the energy sector is proposed. The system considers the impact of the human factor on innovative development at the national, regional and enterprise levels. Also, the need to encourage enterprises to hire highly qualified specialists in the sphere of energy saving and energy efficiency is proven. The role of the tax policy in state regulation of the rational use of energy resources and stimulation of innovation in the energy sector is substantiated. The tax incentives for the rational use of energy resources applied in the world practice are grouped. Features of the application of tax incentives (accelerated depreciation, tax credits, tax holidays, and tax reduction) for energy efficiency and energy saving of households and business entities are analyzed. Directions for stimulating innovation in the energy sector for the efficient use of energy resources are offered.

In 2016, an upsurge of neurologic disease associated with infection with multirecombinant enterovirus A71 subgenogroup C1 lineage viruses was reported in France. These viruses emerged in the 2000s; 1 recombinant is widespread. This virus lineage has the potential to be associated with a long-term risk for severe disease among children.

Despite a large number of proteomic studies of biological fluids from ovarian cancer patients, there is a lack of sensitive screening methods in clinical practice (Kim et al., 2016) (DOI:https://doi.org/10.1111/cas.12987 [1]). Low molecular weight endogenous peptides more easily diffuse across endothelial barriers than proteins and can be more relevant biomarker candidates (Meo et al., 2016) (DOI:https://doi.org/10.18632/oncotarget.8931 [2], (Bery et al., 2014) DOI:https://doi.org/10.1186/1559-0275-11-13 [3], (Huang et al., 2018) DOI:https://doi.org/10.1097/IGC.0000000000001166 [4]). Detailed peptidomic analysis of 26 ovarian cancer and 15 non-cancer samples of biological fluids (ascites and sera) were performed using TripleTOF 5600+ mass-spectrometer. Prior to LC-MS/MS analysis, peptides were extracted from biological fluids using anion exchange sorbent with subsequent peptide desorption from the surface of highly abundant proteins. In total, we identified 4874 peptides; 3123 peptides were specific for the ovarian cancer samples. The mass-spectrometry peptidomics data presented in this data article have been deposited to the ProteomeXchange Consortium (Deutsch et al., 2017) (DOI:https://doi.org/10.1093/nar/gkw936 [5]) via the PRIDE partner repository with the dataset identifier PXD009382 and https://doi.org/10.6019/PXD009382, http://www.ebi.ac.uk/pride/archive/projects/PXD009382.

Blood as connective tissue potentially contains evidence of all processes occurring within the organism, at least in trace amounts (Petricoin et al., 2006) [1]. Because of their small size, peptides penetrate cell membranes and epithelial barriers more freely than proteins. Among the peptides found in blood, there are both fragments of proteins secreted by various tissues and performing their function in plasma and receptor ligands: hormones, cytokines and mediators of cellular response (Anderson et al., 2002) [2]. In addition, in minor amounts, there are peptide disease markers (for example, oncomarkers) and even foreign peptides related to pathogenic organisms and infection agents. To propose an approach for detailed peptidome characterization, we carried out an LC–MS/MS analysis of blood serum and plasma samples taken from 20 healthy donors on a TripleTOF 5600+ mass-spectrometer. We prepared samples based on our previously developed method of peptide desorption from the surface of abundant blood plasma proteins followed by standard chromatographic steps (Ziganshin et al., 2011) [3]. The mass-spectrometry peptidomics data presented in this article have been deposited to the ProteomeXchange Consortium (Deutsch et al., 2017) [4] via the PRIDE partner repository with the dataset identifier PXD008141 and 10.6019/PXD008141.

Point data observations are often used to calibrate computable general equilibrium (CGE) models; however, results may be impacted by calibration of an Armington trade specification in a regional CGE (R-CGE) model. This paper calibrates an Armington trade specification with three differently estimated interregional trade data sets. It estimates interregional trade with one survey and two non-survey methods. The resulting three different trade data sets are each used to calibrate REMES, an R-CGE model for Norway. Two regional policy reforms are simulated with the three model versions to analyze the sensitivity of regional manufacturing sector output to trade data estimates. The results show that the trade data estimation method used for calibration significantly affects regional sector output results. Policy analysts and developers should be aware that calibrating an Armington trade specification with differently estimated interregional trade data may have a substantial influence on model results, and hence, on ex-ante and ex-post conclusions on policy impacts.

Studies overviewed in the paper have yielded a number of new scientific results including the following: suggested is a technique for conducting experimental investigations of electrochemical characteristics of hull structures of ships and floating facilities on the juvenile surface under cathodic polarization in a test seawater solution with the use of the test facility developed for investigating electrochemical characteristics of hull structures of ships and floating facilities on the juvenile surface under cathodic polarization; obtained are the results of laboratory experiments on various shipbuilding steels without surface oxide films in test seawater solutions with a widely ranging salinity spectrum; developed is a neural network-based technique for predicting the protection potential of ships and floating facilities from local corrosion mechanical damages; developed is an algorithm for obtaining the protective potential for hull structures of ships and floating facilities; suggested is a method of protecting hull structures of ships and floating facilities by means of cathodic polarization from local corrosion mechanical damages at the potential of the uncharged surface on the juvenile surface of steel; revealed are beneficial effects of using cathodic polarization by impressed current at the potential of the uncharged surface on the juvenile surface of steel which allow the prolongation of the service life of hull structures of ships and floating facilities.

The purpose of this paper is to investigate the practical aspects of training for parents and teachers of chronically ill children who are under long-term treatment in medical institutions. The paper identifies knowledge, attitudes and practices associated with both formal and non-formal education programs for teachers and parents of children undergoing long-term in-patient treatment. Innovative practices used in Moscow City University are presented, including educational techniques, methods and formats for training teachers and parents of children undergoing long-term treatment together with the results of parent surveys and interviews. The paper describes the benefits of a specially designed program of parent professional retraining to provide tutor support for children with long-term illnesses. Integrating the best informal training practices and formal training modules, this program allows for successful tutoring for children with long-term illnesses.

Genetic interactions, a phenomenon whereby combinations of mutations lead to unexpected effects, reflect how cellular processes are wired and play an important role in complex genetic diseases. Understanding the molecular basis of genetic interactions is crucial for deciphering pathway organization as well as understanding the relationship between genetic variation and disease. Several hypothetical molecular mechanisms have been linked to different genetic interaction types. However, differences in genetic interaction patterns and their underlying mechanisms have not yet been compared systematically between different functional gene classes. Here, differences in the occurrence and types of genetic interactions are compared for two classes, gene-specific transcription factors (GSTFs) and signaling genes (kinases and phosphatases). Genome-wide gene expression data for 63 single and double deletion mutants in baker's yeast reveals that the two most common genetic interaction patterns are buffering and inversion. Buffering is typically associated with redundancy and is well understood. In inversion, genes show opposite behavior in the double mutant compared to the corresponding single mutants. The underlying mechanism is poorly understood. Although both classes show buffering and inversion patterns, the prevalence of inversion is much stronger in GSTFs. To decipher potential mechanisms, a Petri Net modeling approach was employed, where genes are represented as nodes and relationships between genes as edges. This allowed over 9 million possible three and four node models to be exhaustively enumerated. The models show that a quantitative difference in interaction strength is a strict requirement for obtaining inversion. In addition, this difference is frequently accompanied with a second gene that shows buffering. Taken together, these results provide a mechanistic explanation for inversion. Furthermore, the ability of transcription factors to differentially regulate expression of their targets provides a likely explanation why inversion is more prevalent for GSTFs compared to kinases and phosphatases.

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

Background: Recent evidence suggests that speech substantially changes in ageing. As a complex neurophysiological process, it can accurately reflect changes in the motor and cognitive systems underpinning human speech. Since healthy ageing is not always easily discriminable from early stages of dementia based on cognitive and behavioural hallmarks, speech is explored as a preclinical biomarker of pathological itineraries in old age. A greater and more specific impairment of neuromuscular activation, as well as a specific cognitive and linguistic impairment in dementia, unchain discriminating changes in speech. Yet, there is no consensus on such discriminatory speech parameters, neither on how they should be elicited and assessed. Aims: To provide a state-of-the-art on speech parameters that allow for early discrimination between healthy and pathological ageing; the aetiology of these parameters; the effect of the type of experimental stimuli on speech elicitation and the predictive power of different speech parameters; and the most promising methods for speech analysis and their clinical implications. Methods & Procedures: A scoping review methodology is used in accordance with the PRISMA model. Following a systematic search of PubMed, PsycINFO and CINAHL, 24 studies are included and analysed in the review. Main Contribution: The results of this review yield three key questions for the clinical assessment of speech in ageing. First, acoustic and temporal parameters are more sensitive to changes in pathological ageing and, of these two, temporal variables are more affected by cognitive impairment. Second, different types of stimuli can trigger speech parameters with different degree of accuracy for the discrimination of clinical groups. Tasks with higher cognitive load are more precise in eliciting higher levels of accuracy. Finally, automatic speech analysis for the discrimination of healthy and pathological ageing should be improved for both research and clinical practice. Conclusions & Implications: Speech analysis is a promising non-invasive tool for the preclinical screening of healthy and pathological ageing. The main current challenges of speech analysis in ageing are the automatization of its clinical assessment and the consideration of the speaker's cognitive background during evaluation.

One of the key questions of studies on heritage language (HL) transmission is which factors most likely foster the intergenerational transmission of HL and more saliently favor its acquisition in second-generation speakers. The present study explores the effect of the cognitive and affective disposition of first-generation speakers on the subjective HL proficiency level in the second generation of Russian-speaking immigrants in the town of Salamanca, central Spain. Based on a scalar questionnaire which enquires into the language practices, language attitudes and language motivations of the first-generation speakers, the study analyzes the effect of self-categorization, attitudes towards HL utility, and strategies of HL intergenerational transmission in ten mixed families. The main results of the study show that positive HL affectivity is key to assuring proficient HL acquisition in second-generation speakers, while negative HL affectivity systematically drives unbalanced Spanish−Russian bilingualism in children. The final results are consistent with those of other recent studies on affectivity in HL and suggest the importance of positive attitudes towards HL in its transmission.

The article is devoted to research of the main directions and principles of the antropologization of archival science and practices in Belarus. Analysis of theoretical representations starts with the ideas of the Soviet school of an archival science, which appear the ground for the work of the Belarusian archives. The special attention is given to researches of the Polish archivists, where the concept "antropologization of archival science" was used for the first time, and its specifics is defined. By consideration of practical experience of the Belarusian archives presented the aspiration to hold the documents of the concrete personality. Synthesis of the previous theoretical development and available experience in this direction gives an opportunity to mark its main characteristics. As a result was made the conclusion that the anthropological direction of an archival science is one of the most perspective in Belarusian realities, and can become the basis for creation of a new type of archives and preservation of the valuable complex of historical sources.

Desde que Hugo Schuchardt defendiera que toda lengua es un continuum en variación (Abad 1993: 76), como objeto de estudio la variación lingüística ha sido abordada desde múltiples enfoques científicos que se han centrado en la variación tanto como la diversidad dentro del sistema lingüístico como la diversidad entre sistemas lingüísticos distintos.A esta diversidad, concebida no solo como la dialectalidad interna del sistema (Abad 1993: 74) sino también como la heterogeneidad entre sistemas, está dedicado el volumen editado por Esther Hernández y Pedro Martín Butragueño, volumen cuyo fin último, al reunir trabajos de muy variada perspectiva sobre la variación, es ofrecer una definición inclusiva de este concepto indisociable del uso lingüístico.

Phthalocyanines and their analogs have practical interest at development devices with low consumption because these materials are known to considerably modify their electrophysical properties on adsorption of the active gases at low temperatures. The conductivity, resistance-temperature relationship, sensor properties relative to NO, O2 and H2S of films based on oligo-(OPc) and polyphthalocyanines (PPc) containing Co, Cu, Fe and Mn were investigated in the present work. Polymeric films were deposited on the test structures with a pair of interdigital metal electrodes. The sensor’s active area was 4.0 × 4.0 mm, and electrode gap was egual 0.08 mm. The sensitive layers were formed by two methods. The soluble OPcs were deposited from their saturated dimethylformamide solutions and insoluble PPcs were deposited by the thermal sputtering in vacuum. The investigations were carried out under the sensor thermal stabilization conditions in the range 50⁻250 °C with the constant values of the heater resistance.

Dvoimenite toponimi, narekuvani u{te i toponimiski dubleti, toponimiski varijanti ili varijantni toponimi, dosega ne bile predmet na posebni istra`uvawa vo ramkite na makedonskata toponimija. Dvoimenite toponimi go predizvikaa mojot interes u{te vo dale~nata 1965-66 god. koga vr{ev terenski istra`uvawa vo oblasta po slivot na Bregalnica. Motivot za pojavata na dvoimenosta be{e pra{awe koe bara{e odgovor.

Synthesis conditions of doped polyaniline films and testing procedure affect markedly the sensor behavior and stability of them. The sensor based on such film consists of a dielectric substrate with system of metallic interdigitated electrodes on its surface. The films were deposited on system of metallic interdigitated electrodes by electrochemical synthesis from solutions of aniline with different polyoxometalates and acids. Activating additives into films were tungsten containing polyoxometalates of the eighteen series. Polyoxometalates as multielectron oxidants can alter noticeably the sensor properties of polyaniline if introduced into a conductive polymer film. Morphology of the layers surface and the infrared spectra were explored. Investigations of the behavior of polyoxometalate-polyaniline films at different temperatures, air humidity and testing procedures in clean air and in air containing ammonia were fulfilled.

Дана стаття присвячена проблемі формування професійно орієнтованої лексичної компетентності з використанням інформаційно-комунікаційних технологій. Досліджуються особливості процесу навчання іншомовної фахової лексики, визначається поняття лексичної компетентності. Особлива увага приділяється професійно орієнтованій лексичній компетентності, адже процес її формування є невід’ємним компонентом навчання майбутніх спеціалістів різних галузей. Важливу роль у процесі вивчення лексичного матеріалу відіграють інформаційно-комунікаційні технології, адже вони надають можливість оптимізувати та частково автоматизувати процеси вивчення нового матеріалу. ІКТ розраховані на самостійне активне сприймання та засвоєння студентами знань, умінь і навичок. Значна увага приділяється принципам використання ІКТ, яких слід дотримуватися під час навчання лексики, зокрема фахової. Серед них ми виділяємо принцип інтеграції, інтерактивності навчання, індивідуалізації, принцип надання орієнтирів для лексичних дій, а також принцип автоматизованого контролю сформованості лексичних навичок, які є одним з основних елементів професійно орієнтованої лексичної компетентності.

Se hace una reseña del libro Sociolingüística cognitiva. Proposiciones, escolios y debate.

Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus). However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C) species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A-C). In this study, the recombination pattern of EV-C species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99 was determined using partial 5'UTR and VP1 sequences of enterovirus strains isolated during poliovirus surveillance and previously published complete genome sequences. Several inter-typic recombination events were detected. Furthermore, the analyses suggested that inter-typic recombination events have occurred mainly within the distinct sub-groups of EV-C species. Only sporadic recombination events between EV-C species sub-group B and other EV-C sub-groups were detected. In addition, strict recombination barriers were inferred for CVA-21 genotype C and CVA-24 variant strains. These results suggest that the frequency of inter-typic recombinations, even within species, may depend on the phylogenetic position of the given viruses.

Genus Enterovirus (Family Picornaviridae,) consists of twelve species divided into genetically diverse types by their capsid protein VP1 coding sequences. Each enterovirus type can further be divided into intra-typic sub-clusters (genotypes). The aim of this study was to elucidate what leads to the emergence of novel enterovirus clades (types and genotypes). An evolutionary analysis was conducted for a sub-group of Enterovirus C species that contains types Coxsackievirus A21 (CVA-21), CVA-24, Enterovirus C95 (EV-C95), EV-C96 and EV-C99. VP1 gene datasets were collected and analysed to infer the phylogeny, rate of evolution, nucleotide and amino acid substitution patterns and signs of selection. In VP1 coding gene, high intra-typic sequence diversities and robust grouping into distinct genotypes within each type were detected. Within each type the majority of nucleotide substitutions were synonymous and the non-synonymous substitutions tended to cluster in distinct highly polymorphic sites. Signs of positive selection were detected in some of these highly polymorphic sites, while strong negative selection was indicated in most of the codons. Despite robust clustering to intra-typic genotypes, only few genotype-specific 'signature' amino acids were detected. In contrast, when different enterovirus types were compared, there was a clear tendency towards fixation of type-specific 'signature' amino acids. The results suggest that permanent fixation of type-specific amino acids is a hallmark associated with evolution of different enterovirus types, whereas neutral evolution and/or (frequency-dependent) positive selection in few highly polymorphic amino acid sites are the dominant forms of evolution when strains within an enterovirus type are compared.

The paper analyses the importance of behavioural finance theories in household decision-making process. Behavioural finance theories investigate emotional characteristics to explain subjective factors and irrational anomalies in financial markets. In this regard, behavioural theories and behavioural anomalies in the decision-making process are examined; the application opportunities in the financial market are described. The aim of investigation is to determine the basic features and slopes of behavioural finance in concordance with financial decisions of a household. The survey method was applied to ascertain financial behaviour of literate households. Santrauka Straipsnyje nagrinėjama finansinės gyventojų elgsenos teorijų svarba priimant namų ūkių finansinius sprendimus. Finansinės gyventojų elgsenos teorijos tyrinėja rinkos dalyvių emocines charakteristikas, siekiant paaiškinti subjektyvias iracionalias anomalijas finansų rinkose. Straipsnyje išnagrinėtos gyventojų elgsenos teorijos, suklasifikuoti pagrindiniai elgsenos nukrypimai, priimant finansinius sprendimus, ir aprašytos jų pritaikymo finansų rinkoje galimybės. Tyrimo tikslas – nustatyti pagrindinius finansinės elgsenos bruožus ir polinkius sąsajoje su namų ūkių finansiniais sprendimais. Siekiant nustatyti namų ūkių finansinę elgseną buvo atlikta finansiškai išprususių individų apklausa. Raktiniai žodžiai: finansinė elgsena; racionalių finansų paradigma; kognityviniai nukrypimai; ekonominis žmogus; finansiniai sprendimai

Enteroviruses, the most common human viral pathogens worldwide, have been associated with serous meningitis, encephalitis, syndrome of acute flaccid paralysis, myocarditis and the onset of diabetes type 1. In the future, the rapid identification of the etiological agent would allow to adjust the therapy promptly and thereby improve the course of the disease and prognosis. We developed RT-nested PCR amplification of the genomic region coding viral structural protein VP1 for direct identification of enteroviruses in clinical specimens and compared it with the existing analogs. One-hundred-fifty-nine cerebrospinal fluids (CSF) from patients with suspected meningitis were studied. The amplification of VP1 genomic region using the new method was achieved for 86 (54.1%) patients compared with 75 (47.2%), 53 (33.3%) and 31 (19.5%) achieved with previously published methods. We identified 11 serotypes of the Enterovirus species B in 2012, including relatively rare echovirus 14 (E-14), E-15 and E-32, and eight serotypes of species B and 5 enteroviruses A71 (EV-A71) in 2013. The developed method can be useful for direct identification of enteroviruses in clinical material with the low virus loads such as CSF.