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Purpose: To determine the psychological and neuropsychological status of patients with both blast-related ocular injury and mild traumatic brain injury (TBI) late after the traumatic event. Material and Methods: Thirty patients with blast-related ocular injury, reduced visual function and comorbid mild TBI were included in the study. The following methods of psychological and neuropsychological assessment were used: formalized interview; Suicidality, Post-traumatic Stress Disorder (PTSD), Alcohol Dependence, and Drug Dependence scales of the Mini-International Neuropsychiatric Interview (MINI); Raven’s Progressive Matrix scale; Personal and Social Performance (PSP) scale; PROMIS® Pain-Interference scale; Hospital Anxiety and Depression Scale (HADS); Mazes subtest of the Neuropsychological Assessment Battery (NAB); and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results: The following significant correlations were found: PSP functioning and support from the family (r = 0.533, p = 0.002); total RBANS score and Mazes subtest score (r = 0.466, p = 0.009); total RBANS score and self-reported stress score (negative correlation, r = -0.492, p = 0.006); HADS depression and self-reported stress score (r = 0.646, p = 0.000114); PROMIS pain scale and PTSD scale (r = 0.482, p = 0.007). No association was found between the number of mild TBI events experienced and neuropsychological and psychological measurements. Conclusion: Blast-related mild TBI concomitant with ocular injury has a substantial and long-term impact on casualty’s cognitive and psychological functions. In such patients, the most prominent cognitive deficits occur in the domain of executive function (including cognitive control and planning and problem-solving skills). In the presence of reduced visual function, these deficits have a substantial impact on total cognitive scores, scores of other psychic functions (namely, attention and memory) and significantly affect the patient’s capacity for independent functioning.

The article examines the application of the concept of legal pluralism to the interaction between the European Union (EU) administrative legal order and the administrative legal orders of associated or candidate States as part of the process of aligning national legislation with EU standards. This process involves multiple sources of integration obligations derived from the Association Agreement, accession negotiations, conditions for economic aid, administrative cooperation, and EU-funded modernization programs. The authors suggest that a pluralistic approach may provide associated or candidate States with a degree of flexibility in choosing specific scopes, models, and time frames to align their national legislation with EU laws. This can help to mitigate and offset the imbalance in States’ relations with the EU resulting from the latter’s normative dominance. At the same time, various sources can lead to conflicts between integration obligations and approaches to harmonizing national administrative rules and practices.

Abstract Background Patient-focused approaches to capturing day-to-day variability in sleep disturbance are needed to properly evaluate the sleep benefits of new treatments. Such approaches rely on patient-reported outcome (PRO) measures validated in the target patient population. Methods Using atopic dermatitis (AD) as an example of a disease in which sleep is commonly disturbed, we developed a strategy for measuring sleep disturbance in AD trials. In developing this strategy, we conducted a targeted literature review and held concept elicitation interviews with adolescents and adults with AD. We subsequently identified potentially suitable PRO measures and cognitively debriefed them. Finally, we evaluated their psychometric properties using data from phase 2b (NCT03100344) and phase 3 (NCT03985943 and NCT03989349) clinical trials. Results The literature review confirmed that sleep disturbance is a key impact of AD but failed to identify validated PRO measures for assessing fluctuations in sleep disturbance. Subsequent concept elicitation interviews confirmed the multidimensional nature of sleep disturbance in AD and supported use of a single-item measure to assess overall sleep disturbance severity, complemented by a diary to capture individual components of sleep disturbance. The single-item sleep disturbance numerical rating scale (SD NRS) and multi-item Subject Sleep Diary (SSD)—an AD-adapted version of the Consensus Sleep Diary—were identified as potentially suitable PRO measures. Cognitive debriefing of the SD NRS and SSD demonstrated their content validity and their understandability to patients. Psychometric analyses based on AD trial data showed that the SD NRS is a well-defined, reliable, and fit-for-purpose measure of sleep disturbance in adults with AD. Furthermore, the SD NRS correlated with many SSD sleep parameters, suggesting that most concepts from the SSD can be covered using the SD NRS. Conclusions Using these findings, we developed an approach for measuring sleep disturbance in AD trials. Subject to further research, the same approach could also be applied to future trials of other skin diseases where itch causes sleep disturbance.

Abstract Transport of macromolecules through the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs) consisting of nucleoporins (Nups). Elys/Mel-28 is the Nup that binds and connects the decondensing chromatin with the reassembled NPCs at the end of mitosis. Whether Elys links chromatin with the NE during interphase is unknown. Here, using DamID-seq, we identified Elys binding sites in Drosophila late embryos and divided them into those associated with nucleoplasmic or with NPC-linked Elys. These Elys binding sites are located within active or inactive chromatin, respectively. Strikingly, Elys knockdown in S2 cells results in peripheral chromatin displacement from the NE, in decondensation of NE-attached chromatin, and in derepression of genes within. It also leads to slightly more compact active chromatin regions. Our findings indicate that NPC-linked Elys, together with the nuclear lamina, anchors peripheral chromatin to the NE, whereas nucleoplasmic Elys decompacts active chromatin.

La enfermería es la labor que abarca la atención autónoma a personas de todas las edades, familias, grupos y comunidades, la principal característica y esencia es el cuidado, implica establecer una relación de comprensión y acompañamiento de manera integral, convirtiéndolos en los principales cuidadores formales en la asistencia, lo que pone de manifiesto la necesidad de mirar su salud mental y bienestar del personal de enfermería. El objetivo fue describir el impacto en la salud mental de un profesional de la enfermería en la atención a pacientes del área COVID en tiempos de pandemia, en el periodo 2022-2023. Se realizó un estudio cualitativo, primero mediante el análisis documental y posteriormente mediante el método fenomenológico, descriptivo con base en el estudio de caso, considerando la temporalidad en tres momentos, antes, durante y después de la pandemia por COVID. Los hallazgos dan constancia, de cambios e impactos a nivel biológico, psicológico, social y espiritual que derivan en afectaciones en salud mental que se experimentaron, y, por otro lado, de la escasez acciones para dotar a los profesionales de la salud de un acompañamiento, capacitación y sensibilización en salud mental para la mejora de su labor y bienestar personal.

La relación de las emociones y los procesos cognitivos ha posicionado a la educación emocional como un tema relevante en el ámbito educativo; sin embargo, para lograr su plena integración en la educación superior resulta imperativo conocer el estado que guarda en la actualidad. El objetivo del estudio consiste en identificar los principales hallazgos teóricos y empíricos relacionados con la educación emocional en el nivel superior, la educación emocional en el proceso de enseñanza-aprendizaje y la formación del docente universitario en educación emocional. Para ello se realizó una revisión documental con enfoque cualitativo y descriptivo, utilizando repositorios y bases de datos científicas. Se incluyeron artículos en español e inglés publicados en México y en el extranjero, entre los años 2017 y 2022. Se revisaron 67 documentos y se seleccionaron 22 que fueron organizados en tres categorías: a) educación emocional en el nivel superior, b) educación emocional en el proceso de enseñanza-aprendizaje y c) formación docente en educación emocional. Los principales hallazgos evidencian que la educación emocional tiene una influencia positiva en el rendimiento académico y la generación de ambientes propicios en el aula, pero también la urgente necesidad de una formación docente y el afrontamiento de desafíos...

Abstract The phenyl ring is a basic structural element in chemistry. Here, we show the design, synthesis, and validation of its new saturated bioisostere with improved physicochemical properties − 2-oxabicyclo[2.2.2]octane. The design of the structure is based on the analysis of the advantages and disadvantages of the previously used bioisosteres: bicyclo[1.1.1]pentane, bicyclo[2.2.2]octane, and cubane. The key synthesis step is the iodocyclization of cyclohexane-containing alkenyl alcohols with molecular iodine in acetonitrile. 2-Oxabicyclo[2.2.2]octane core is incorporated into the structure of Imatinib and Vorinostat (SAHA) drugs instead of the phenyl ring. In Imatinib, such replacement leads to improvement of physicochemical properties: increased water solubility, enhanced metabolic stability, and reduced lipophilicity. In Vorinostat, such replacement results in a new bioactive analog of the drug. This study enhances the repertoire of available saturated bioisosteres of (hetero)aromatic rings for the use in drug discovery projects.

Abstract Introduction Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. Methods A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator’s Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. Results A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Conclusion Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.

Abstract The fossil vertebrate fauna of Máriahalom contains remains from a wide range of ecologies including terrestrial and aquatic mammals, crocodiles, sharks, and rays among others. All these were found mixed in mollusc-rich, shallow water, coastal deposits. The aim of the study is to trace the origin of the fossils using their rare earth element (REE) content and their respective ecology with stable oxygen isotopic compositions. In addition, marine vertebrates and calcareous marine fossils were analysed for their Sr isotope composition to provide a new age estimate for the locality. The REE content and their distribution in the fossils indicate similar early diagenetic environments and possible contemporaneous fossilization for the entire vertebrate assemblage. Reworked fossils of significantly different age can be excluded. The enamel/enameloid-derived phosphate oxygen isotope composition of selected fossil taxa fit well with previously inferred habitats that include marine, brackish, and terrestrial environments. Notably, the stem-pinniped Potamotherium valletoni is best interpreted as freshwater dweller instead of marine, consistent with the sedimentology of other occurrences. Our novel 87Sr/86Sr data suggest an Aquitanian age (21.4 ± 0.5 Ma) for the Máriahalom site that is younger than the previously proposed Late Oligocene age based on biostratigraphy (MP28–30 European Mammal Paleogene Reference Levels). An Aquitanian age raises the possibility that the index fossil taxon, the anthracothere mammal Microbunodon minimum, may have vanished earlier in Western Europe than in the Central Paratethys region.

Background. The relevance of studying the phenomenon of public catering in the USSR is due to the need to understand the specifics of the Soviet modernity, the implemen-tation of the project of building a new society in the conditions of Stalin’s reconstruction of the national economy. The purpose of the work is to analyze the process of changes in the functioning of public catering in the 1920s – 1930s on the example of Penza region. Materials and methods. Based on the study of a wide range of sources extracted from the central (Russian State Archive of Economics) and local archives (State Archive of Penza region), as well as published documents, the features of the formation of a key branch of the modern economy – public catering in the period of the 1920s – 1930s are revealed. The methodological basis of the study was the concept of social constructionism or con-structivism, in the context of which the main emphasis is placed on the conditionality of the processes of constructing social reality by state ideology and management practice. Com-parative historical and statistical methods were used to identify the regional specifics of the formation of the Soviet public catering. Results. The main principles, features, advantages and disadvantages of the Soviet public catering in various historical periods – the new eco-nomic policy of the 1920s and industrialization of the 1930s – are analyzed on the example of Penza region. Conclusions. In the period of the 1920s – 1930s, continuity in the work of public canteens of Penza province was maintained: class orientation, advantages and problems characteristic of the previous period. A new trend was a temporary relaxation for private capital admitted to the catering sector in the 1920s. During the years of industriali-zation, it became one of the branches of the Soviet economy that contributed to the solution of important state tasks.

Current rail traffic management and control systems cannot be easily upgraded to the new needs and challenges of modern railway systems because they do not offer interoperable data structures and standardized communication interfaces. To meet this need, the Horizon 2020 Shift2Rail OPTIMA project has developed a communication platform for testing and validating the new generation of traffic management systems (TMS), whose main innovative features are the interoperability of the data structures used, standardization of communications, continuous access to real-time and persistent data from heterogeneous data sources, modularity of components and scalability of the platform. This paper presents the main components, their functions and characteristics, then describes the testing and validation of the platform, even when federated with other innovative TMS modules developed in separate projects. The successful validation of the system has confirmed the achievement of the objectives set and allowed a new set of objectives to be defined for the reference platform for the railway TMS/Traffic Control systems.

Introducción: La pandemia por COVID-19 interrumpió abruptamente la modalidad educativa presencial, los docentes se adaptaron a una nueva forma de enseñanza mediada con tecnología como respuesta al confinamiento. Al respecto, la Universidad de Colima, en México, ejecutó un Programa de Continuidad Académica para garantizar la atención del estudiantado en bachillerato, licenciatura y posgrado. Objetivo: El articulo describe la situación tecnológica, pedagógica-didáctica y socioemocional que enfrentaron los docentes del nivel superior, en el desarrollo de este programa universitario, así como las necesidades de capacitación y los principales retos del profesorado en la enseñanza mediada. Metodología: Estudio mixto de tipo exploratorio, resultado de la aplicación de un cuestionario a 1 587 docentes, de los cuales se obtuvieron 1 195 respuestas. R­esultados y discusión: En la investigación se evidenció que, el 63% de los docentes enfrentó complicaciones de tipo didácticas-pedagógicas; el 17% tecnológicas y de logística y el 7% de tipo emocional al tiempo de conducir la «nueva» forma de enseñanza. Conclusiones: Los retos del docente ante la pandemia permiten visualizar las demandas de formación, capacitación, actualización y desarrollo de habilidades del profesorado, así como la apropiación de los recursos tecnológicos que limita el desarrollo de los procesos de enseñanza aprendizaje acordes a la calidad educativa esperada. Asimismo, se propone continuar con esta línea de investigación orientada a identificar prácticas creativas y necesidades de capacitación docente, desde la perspectiva del estudiantado, y con ello, fortalecer la oferta académica del Programa Institucional de Formación Docente en función de la mejora del desempeño del profesorado universitario.

Abstract Proximity ligation approaches, which are widely used to study the spatial organization of the genome, also make it possible to reveal patterns of RNA-DNA interactions. Here, we use RedC, an RNA-DNA proximity ligation approach, to assess the distribution of major RNA types along the genomes of E. coli, B. subtilis, and thermophilic archaeon T. adornatum. We find that (i) messenger RNAs preferentially interact with their cognate genes and the genes located downstream in the same operon, which is consistent with polycistronic transcription; (ii) ribosomal RNAs preferentially interact with active protein-coding genes in both bacteria and archaea, indicating co-transcriptional translation; and (iii) 6S noncoding RNA, a negative regulator of bacterial transcription, is depleted from active genes in E. coli and B. subtilis. We conclude that the RedC data provide a rich resource for studying both transcription dynamics and the function of noncoding RNAs in microbial organisms.

Purpose. The work is aimed to determine the real location in space and conduct possible measurement of the true geometric dimensions of the NPP cooling pond dam, especially its underwater part and to detect the additional and previously unaccounted factors that could affect these parameters, as well as the state of the entire structure in general. Methodology. A comprehensive analysis of all available materials about engineering surveys and geotechnical studies was carried out at the dam of the cooling pond of the Zaporizhzhia NPP. Due to this, a more comprehensive look at the results of engineering and geological surveys was obtained. Findings. The state of soils in the body of the earth dam can be influenced by weakened and poorly studied zones of the dam. These zones were determined based on the analysis of the soil studies data of the dam’s ground. Previously uncovered issues on the operation of the facility were raised and considered. The ways and methods for additional study of the earth dam of the cooling pond were selected, the conditions for their use were substantiated. A numerical relationship between the thickness of loose soils and the amount of surface subsidence were determined for the first time. A generalized geological section of the dam body was compiled for further modeling of geotechnical processes. Originality. For the first time since construction, a comprehensive program was developed for assessing the technical condition of the cooling pond dam using innovative methods from the Laboratory of Research of Nuclear and Thermal Power Plants in Prydniprovska State Academy of Civil Engineering and Architecture (PSACEA). In particular, combined hydrographic-geodetic and aerovisual methods were proposed using specially designed universal leading signs that have no analogues in world practice. Practical value. The application of the developed comprehensive program using innovative methods allows assessing the technical condition of the cooling pond dam of the NPP.

Abstract Background Understanding the role of various factors in 3D genome organization is essential to determine their impact on shaping large-scale chromatin units such as euchromatin (A) and heterochromatin (B) compartments. At this level, chromatin compaction is extensively modulated when transcription and epigenetic profiles change upon cell differentiation and response to various external impacts. However, detailed analysis of chromatin contact patterns within and between compartments is complicated because of a lack of suitable computational methods. Results We developed a tool, Pentad, to perform calculation, visualisation and quantitative analysis of the average chromatin compartment from the Hi-C matrices in cis, trans, and specified genomic distances. As we demonstrated by applying Pentad to publicly available Hi-C datasets, it helps to reliably detect redistribution of contact frequency in the chromatin compartments and assess alterations in the compartment strength. Conclusions Pentad is a simple tool for the analysis of changes in chromatin compartmentalization in various biological conditions. Pentad is freely available at https://github.com/magnitov/pentad .

Ganoderma lucidum exhibits the ability to synthesize a diverse range of biologically active molecules with significant pharmaceutical potential, including xylomannan and fucogalactan, which have demonstrated antitumor activity. However, there exists considerable intra-species variability in the capacity to produce these metabolites at high concentrations, likely reflecting the high genomic diversity observed from a limited number of strains sequenced to date. We employed high-throughput shotgun sequencing to obtain the complete genome sequence of G. lucidum strain 5.1, which is distinguished by its remarkable xylomannan synthesis capabilities. Through the utilization of semi-automatic reordering based on conformation capture (Hi-C) data, we substantially enhanced the assembly process, resulting in the generation of 12 chromosome-level scaffolds with a cumulative length of 39 Mbp. By employing both de novo and homology-based approaches, we performed comprehensive annotation of the genome, thereby identifying a diverse repertoire of genes likely involved in polysaccharide biosynthesis. The genome sequence generated in this study serves as a valuable resource for elucidating the molecular mechanisms underlying the medicinal potential of Ganoderma species, discovering novel pharmaceutically valuable compounds, and elucidating the ecological mechanisms of the species. Furthermore, the chromosome contact map obtained for the first time for this species extends our understanding of 3D fungal genomics and provides insights into the functional and structural organization within the fungal kingdom.

Zygotic genome activation in zebrafish relies on pluripotency transcription factors Pou5f3 and Sox19b. Here the authors investigate how these factors interact in vivo by analyzing the changes in chromatin state and time-resolved transcription in Pou5f3 and Sox19b single and double mutant embryos.

Abstract The Barrovian metamorphism of the Lepontine dome is manifested by isograds that cross‐cut tectonic nappe contacts, which is commonly interpreted as metamorphism that occurred after nappe emplacement. However, the pervasive mineral and stretching lineation in amphibolite facies, associated with top‐to‐foreland shearing, suggests that peak Barrovian conditions are coeval with nappe‐overthrusting. Here, we combine mapping and U‐Pb zircon dating to better constrain the relation between metamorphism and overthrusting. Metamorphic zircon rims show two age populations at 31–33 and 22–24 Ma. The younger population is locally observed in post‐foliation dikes (and associated metasomatism) likely sourced from deep‐migmatites exhuming along the Alpine backstop. The older population occurs regionally and is found in syn‐kinematic migmatites which occur along a crustal‐scale shear zone. Below this shear zone, magmatic and detrital zircon cores suggest that the Cima Lunga unit, previously interpreted as a tectonic mélange with Mesozoic fragments, was a pre‐Variscan metasedimentary sequence intruded by Permian granitic sills, now orthogneisses. This unit was strongly sheared along the top of the Simano nappe during overthrusting of a rock pile here‐termed Maggia‐Adula nappe. This large‐scale nappe emplacement imprinted the regional lineation and peak temperatures until 31–33 Ma. Péclet (1–10) and Brinkman (0.002–1.8) numbers, estimated for the overthrusting, suggest an advection‐dominated heat transfer caused by rock exhumation, with some diffusion (conduction) during nappe emplacement. Diffusion contributed to Barrovian isograds discordant to the thrust. Shear heating was important if stress times shearing rate >∼5·10−6 W·m−3 within the nappe. The thermal evolution after overthrusting was spatially heterogeneous until ca. 22 Ma.

Introducción: la insuficiencia venosa es una afectación en la cual las venas son incapaces de enviar sangre desde las extremidades inferiores al corazón. La gravedad de esta enfermedad radica en sus complicaciones, el grado más leve produce escozor, dolor, pesadez, cansancio y quemazón en la planta de los pies; al complicarse puede presentar edema, calambres en pantorrillas, prurito intenso y coloración oscura de la piel. Objetivo: describir el nivel de conocimiento y cumplimiento del personal de enfermería de área quirúrgica respecto al autocuidado relacionado a la insuficiencia venosa de miembros inferiores. Material y métodos: se trata de un estudio descriptivo, trasversal, prolectivo y observacional; el universo es de 24 profesionales en enfermería y la muestra estuvo conformada por 22 colaboradores adscritos al área quirúrgica de un hospital público de segundo nivel de atención; se utilizaron dos instrumentos: 1) conocimiento y 2) cuestionario para evaluar el autocuidado. Se analizaron los datos mediante estadística descriptiva y prueba exacta de Fisher. Resultados: el 100 % de los participantes en el estudio no cumple con el autocuidado, el criterio para determinar el cumplimiento fue que, al observar las acciones preventivas conocidas como autocuidado, se obtuviera una calificación de 6 ítems completos, lo cual no sucede. Conclusión: existe un factor de riesgo para la insuficiencia venosa en miembros inferiores, donde la antigüedad laboral es la variable que evidencia diferencias significativas con respecto al conocimiento y cumplimiento.

This article presents a clinical review of a patient with an extremely rare assotiation of opticoneuromyelitis and skin melanoma. The paper noted the typical clinical and neuroimaging signs of opticoneuromyelitis and the rare manifestations of myelitic syndrome such as segmental muscle hypertonicity and hand hyperkinesis. The question remains open as to whether these two processes in a patient are linked by a single pathogenesis in the form of a paraneoplastic neurological syndrome or whether two independent diseases are represent there. Two observations of a combination of melanoma and opticoneuromyelitis as a manifestation of the paraneoplastic syndrome have been analysed in the literature. The article highlights the difficulties in the treatment of this patient, as the immunomodulatory therapy used for both diseases has a different vectorial focus. Immunosuppression is recommended for the treatment of opticoneuromyelitis, while immune activation is recommended for melanoma.

El estudio propone una clasificación de estrategias de gestión del conocimiento para impulsar la innovación educativa en Instituciones de Educación Superior. Para lograrlo se realizó un análisis documental. Los resultados aluden a la consolidación creativa e innovadora de la educación a través de la gestión escolar, por lo que ésta, deberá apoyarse en aspectos como pensamiento complejo, procesos de innovación, tecnologías de la información y la comunicación y estrategias o métodos de gestión del conocimiento que aseguren que el saber interno y externo sea compartido para que pueda ser transmitido y asimilado. La clasificación de estrategias se basa en los niveles organizacional y pedagógico-didáctico de la gestión escolar, y ocho procesos del conocimiento divididos en exploración y explotación. Finalmente, se sugieren futuros análisis de prácticas y estrategias implementadas en IES, y con los resultados, se planteen estrategias organizacionales.

El estudio propone una clasificación de estrategias de gestión del conocimiento para impulsar la innovación educativa en Instituciones de Educación Superior. Para lograrlo se realizó un análisis documental. Los resultados aluden a la consolidación creativa e innovadora de la educación a través de la gestión escolar, por lo que ésta, deberá apoyarse en aspectos como pensamiento complejo, procesos de innovación, tecnologías de la información y la comunicación y estrategias o métodos de gestión del conocimiento que aseguren que el saber interno y externo sea compartido para que pueda ser transmitido y asimilado. La clasificación de estrategias se basa en los niveles organizacional y pedagógico-didáctico de la gestión escolar, y ocho procesos del conocimiento divididos en exploración y explotación. Finalmente, se sugieren futuros análisis de prácticas y estrategias implementadas en IES, y con los resultados, se planteen estrategias organizacionales.

Abstract Chromatin loops represent one of the major levels of hierarchical folding of the genome. Although the situation is evolving, current methods have various difficulties with the accurate mapping of loops even in mammalian Hi-C data, and most of them fail to identify chromatin loops in animal species with substantially different genome architecture. This paper presents the loop and significant contact annotation (LASCA) pipeline, which uses Weibull distribution-based modeling to effectively identify loops and enhancer–promoter interactions in Hi-C data from evolutionarily distant species: from yeast and worms to mammals. Available at: https://github.com/ArtemLuzhin/LASCA_pipeline .

Genomes are partitioned into topologically associating domains (TADs). Here the authors present single-nucleus Hi-C maps in Drosophila at 10 kb resolution, demonstrating the presence of chromatin compartments in individual nuclei, and partitioning of the genome into non-hierarchical TADs at the scale of 100 kb, which resembles population TAD profiles.

Abstract Chromatin communities stabilized by protein machinery play essential role in gene regulation and refine global polymeric folding of the chromatin fiber. However, treatment of these communities in the framework of the classical network theory (stochastic block model, SBM) does not take into account intrinsic linear connectivity of the chromatin loci. Here we propose the polymer block model, paving the way for community detection in polymer networks. On the basis of this new model we modify the non-backtracking flow operator and suggest the first protocol for annotation of compartmental domains in sparse single cell Hi-C matrices. In particular, we prove that our approach corresponds to the maximum entropy principle. The benchmark analyses demonstrates that the spectrum of the polymer non-backtracking operator resolves the true compartmental structure up to the theoretical detectability threshold, while all commonly used operators fail above it. We test various operators on real data and conclude that the sizes of the non-backtracking single cell domains are most close to the sizes of compartments from the population data. Moreover, the found domains clearly segregate in the gene density and correlate with the population compartmental mask, corroborating biological significance of our annotation of the chromatin compartmental domains in single cells Hi-C matrices.

Rare earth elements (REEs) and yttrium in seawater originate from atmospheric fallout, continental weathering, and transport from rivers, as well as hydrothermal activity. Previous studies have reported the use of REE and Y measurements in biogenic carbonates as a means to reconstruct these surface processes in ancient times. As coastal seawater REE and Y concentrations partially reflect those of nearby rivers, it may be possible to obtain a regional fingerprint of these concentrations from bivalve shells for seafood traceability and environmental monitoring studies. Here, we present a dataset of 297 measurements of REE and Y abundances by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) from two species (Crassostrea gigas and Ostrea edulis). We measured a total of 49 oyster specimens from six locations in France (Atlantic Ocean and Mediterranean Sea). Our study reports that there is no significant difference in concentrations from shell parts corresponding to winter and summer periods for both species. Moreover, interspecific vital effects are reported from specimens from both species and from the same locality. REE and Y profiles as well as t-distributed stochastic neighbour embedding processing (t-SNE; a discriminant statistical method) indicate that REE and Y measurements from C. gigas shells can be discriminated from one locality to another, but this is not the case for O. edulis, which presents very similar concentrations in all studied localities. Therefore, provenance studies using bivalve shells based on REEs and Y have to first be tested for the species. Other methods have to be investigated to be able to find the provenance of some species, such as O. edulis.

Universities face a permanent process of transformation, so they need to manage internal educational knowledge to accelerate innovation, regardless of their educational modality. However, there are few contributions that address the evaluation of the level of maturity in what they do. Therefore, the questionnaire maturity of knowledge management to innovate in universities was designed and validated. For this purpose, a review of existing instruments was carried out, the questionnaire was designed using a Likert-type structure, which was later analyzed by seven experts, its content was validated by 15 expert judgements with a qualitative-quantitative approach, and it was applied to a pilot group of 15 professors for analysis of comprehension of both items and instructions. The instrument was formed by five dimensions and 48 items. The experts specified improvements and determined the relevance of the dimensions and items; the analysis of Judges evaluation revealed the content validity of items in terms of relevance and writing (V of Aiken> 0.90); the pilot group deemed with a good grade the understanding of instructions, the items and instrument satisfaction with a relevant initial reliability value (Cronbach’s alpha: 0.941). It is recommended to apply it to a representative sample for analysis of construct validity, and reliability.

Abstract The transition from a linear economy to a circular economy is a significant component of economic, environmental and social sustainability. Underground metro infrastructures such as tunnels can play a vital role in a circular economy, resulting in greater sustainability and less contribution to climate change. This paper presents numerical models of small-scale brick-lined railway tunnels to identify the critical locations, and then proposes corresponding circular approaches and solutions for the design, maintenance, life extension and end-of-service-life (EoSL) stages of underground infrastructures. The proposed numerical model is firstly verified with respect to the relevant experimental model based on tests under various loading conditions. The results demonstrate that detailed failure processes can be realistically captured by the numerical model, while the macroscopic behaviour compares well with experimental observations. Numerical modelling and subsequent prediction stand out as a practical approach and a powerful performance-based tool for analysing the reuse/recycling potential of metro tunnels and then carrying out easy repair and design for adaptability, disassembly and recoverability of underground infrastructures for a circular economy.

Gut microbiome in critically ill patients shows profound dysbiosis. The most vulnerable is the subgroup of chronically critically ill (CCI) patients – those suffering from long-term dependence on support systems in intensive care units. It is important to investigate their microbiome as a potential reservoir of opportunistic taxa causing co-infections and a morbidity factor. We explored dynamics of microbiome composition in the CCI patients by combining “shotgun” metagenomics with chromosome conformation capture (Hi-C). Stool samples were collected at 2 time points from 2 patients with severe brain injury with different outcomes within a 1–2-week interval. The metagenome-assembled genomes (MAGs) were reconstructed based on the Hi-C data using a novel hicSPAdes method (along with the bin3c method for comparison), as well as independently of the Hi-C using MetaBAT2. The resistomes of the samples were derived using a novel assembly graph-based approach. Links of bacteria to antibiotic resistance genes, plasmids and viruses were analyzed using Hi-C-based networks. The gut community structure was enriched in opportunistic microorganisms. The binning using hicSPAdes was superior to the conventional WGS-based binning as well as to the bin3c in terms of the number, completeness and contamination of the reconstructed MAGs. Using Klebsiella pneumoniae as an example, we showed how chromosome conformation capture can aid comparative genomic analysis of clinically important pathogens. Diverse associations of resistome with antimicrobial therapy from the level of assembly graphs to gene content were discovered. Analysis of Hi-C networks suggested multiple “host-plasmid” and “host-phage” links. Hi-C metagenomics is a promising technique for investigating clinical microbiome samples. It provides a community composition profile with increased details on bacterial gene content and mobile genetic elements compared to conventional metagenomics. The ability of Hi-C binning to encompass the MAG’s plasmid content facilitates metagenomic evaluation of virulence and drug resistance dynamics in clinically relevant opportunistic pathogens. These findings will help to identify the targets for developing cost-effective and rapid tests for assessing microbiome-related health risks.

El estudio propone una clasificación de estrategias de gestión del conocimiento para impulsar la innovación educativa en Instituciones de Educación Superior. Para lograrlo se realizó un análisis documental. Los resultados aluden a la consolidación creativa e innovadora de la educación a través de la gestión escolar, por lo que ésta, deberá apoyarse en aspectos como pensamiento complejo, procesos de innovación, tecnologías de la información y la comunicación y estrategias o métodos de gestión del conocimiento que aseguren que el saber interno y externo sea compartido para que pueda ser transmitido y asimilado. La clasificación de estrategias se basa en los niveles organizacional y pedagógico-didáctico de la gestión escolar, y ocho procesos del conocimiento divididos en exploración y explotación. Finalmente, se sugieren futuros análisis de prácticas y estrategias implementadas en IES, y con los resultados, se planteen estrategias organizacionales. English abstract This research proposes a classification of Knowledge Management Strategies in order to enhance educational innovation in Higher Education Institutions. To achieve this a documentary analysis was used. The results allude to the creative and innovative consolidation of education through school management, so this should be supported by aspects such as complex thinking, innovation processes, information and communication technologies and strategies or methods of management of the knowledge that ensures that internal and external knowledge is shared so that it can be transmitted and assimilated. The classification of strategies is based on the organizational and pedagogical-didactic levels of school management, and eight knowledge processes divided into exploration and exploitation. Finally, future analysis of practices and strategies implemented are suggested, and from it, the design of a goal-strategy.

Background. Leasing land is a widespread phenomenon in the life of a reform village in any region of European Russia in the second half of the 19th – early 20th centuries. By the level of development of rental relations, one can judge the state of the landowner and peasant economy of a particular province, the degree of development of capitalist relations in it. This determines the relevance of the work. The purpose of the work is to characterize rental relations in one of the large landowner farms of the Penza province of the second half of the 19th – early 20th centuries in the context of the development of the entire region. Materials and methods. Based on the study of a wide range of sources, including archival data of the State Archive of the Penza Region, as well as published documents of state central statistical agencies and primary materials collected by contemporaries, an attempt was made to solve the tasks of the study. In the process of work, comparative historical, statistical methods were used. Results. An analysis of the sources showed that the landowner’s farm in question was one of the large estates of the Chembar district in the Penza province, most of whose land was leased for short and long-term rent, which was the norm for the province under study. The tenants were the local peasantry. On part of the leased territories, the owners, at their own expense, equipped rental farms. Conclusions. Leasing land was an indispensable attribute of the landowner Stolypin in the village of Tarkhany throughout the period under consideration. Over time, rental relations have undergone a noticeable evolution, constantly becoming more complicated, improving and bringing more income to owners. The Tarkhany estate itself is an example of the successful integration of the landowner economy into the development of new agrarian capitalist relations.

El estudio propone una clasificación de estrategias de gestión del conocimiento para impulsar la innovación educativa en Instituciones de Educación Superior. Para lograrlo se realizó un análisis documental. Los resultados aluden a la consolidación creativa e innovadora de la educación a través de la gestión escolar, por lo que ésta, deberá apoyarse en aspectos como pensamiento complejo, procesos de innovación, tecnologías de la información y la comunicación y estrategias o métodos de gestión del conocimiento que aseguren que el saber interno y externo sea compartido para que pueda ser transmitido y asimilado. La clasificación de estrategias se basa en los niveles organizacional y pedagógico-didáctico de la gestión escolar, y ocho procesos del conocimiento divididos en exploración y explotación. Finalmente, se sugieren futuros análisis de prácticas y estrategias implementadas en IES, y con los resultados, se planteen estrategias organizacionales. English abstract This research proposes a classification of Knowledge Management Strategies in order to enhance educational innovation in Higher Education Institutions. To achieve this a documentary analysis was used. The results allude to the creative and innovative consolidation of education through school management, so this should be supported by aspects such as complex thinking, innovation processes, information and communication technologies and strategies or methods of management of the knowledge that ensures that internal and external knowledge is shared so that it can be transmitted and assimilated. The classification of strategies is based on the organizational and pedagogical-didactic levels of school management, and eight knowledge processes divided into exploration and exploitation. Finally, future analysis of practices and strategies implemented are suggested, and from it, the design of a goal-strategy.

Construction of chromosomes 3D models based on single cell Hi-C data constitute an important challenge. We present a reconstruction approach, DPDchrom, that incorporates basic knowledge whether the reconstructed conformation should be coil-like or globular and spring relaxation at contact sites. In contrast to previously published protocols, DPDchrom can naturally form globular conformation due to the presence of explicit solvent. Benchmarking of this and several other methods on artificial polymer models reveals similar reconstruction accuracy at high contact density and DPDchrom advantage at low contact density. To compare 3D structures insensitively to spatial orientation and scale, we propose the Modified Jaccard Index. We analyzed two sources of the contact dropout: contact radius change and random contact sampling. We found that the reconstruction accuracy exponentially depends on the number of contacts per genomic bin allowing to estimate the reconstruction accuracy in advance. We applied DPDchrom to model chromosome configurations based on single-cell Hi-C data of mouse oocytes and found that these configurations differ significantly from a random one, that is consistent with other studies. Author summary Reconstruction of 3D configuration of chromosomes based on single cell Hi-C data (contact matrix) constitutes an important way to understand the specific features of genome packaging in individual cells. For this purpose, we develop method DPDchrom based on dissipative particle dynamics. Two sources of the contact dropout, contact radius change and random contact sampling, have different impact to the reconstruction accuracy suggesting unequal value of contacts. We found the exponential dependence of the reconstruction accuracy on the number of contacts per genomic bin. We reconstructed entire nucleus of mouse using single cell Hi-C data and found significant dissimilarity of conformations reconstructed using experimental and shuffled data. These findings open perspectives to study 3D arrangement of cis-regulatory elements orchestrating transcription program.

Construction of chromosomes 3D models based on single cell Hi-C data constitute an important challenge. We present a reconstruction approach, DPDchrom, that incorporates basic knowledge whether the reconstructed conformation should be coil-like or globular and spring relaxation at contact sites. In contrast to previously published protocols, DPDchrom can naturally form globular conformation due to the presence of explicit solvent. Benchmarking of this and several other methods on artificial polymer models reveals similar reconstruction accuracy at high contact density and DPDchrom advantage at low contact density. To compare 3D structures insensitively to spatial orientation and scale, we propose the Modified Jaccard Index. We analyzed two sources of the contact dropout: contact radius change and random contact sampling. We found that the reconstruction accuracy exponentially depends on the number of contacts per genomic bin allowing to estimate the reconstruction accuracy in advance. We applied DPDchrom to model chromosome configurations based on single-cell Hi-C data of mouse oocytes and found that these configurations differ significantly from a random one, that is consistent with other studies.

The article is devoted to the memory of Professor Oleg V. Beydik. His career and professional development described.

Objective To explore decision support systems (DSS) used in spine-pelvic surgery, analyze its functional possibilities and approaches that allow the surgeon to make a correct decision. Material and methods Functional possibilities with modern DSSs used in surgery of spine-pelvic complex were reviewed with unified criteria using websites of DSS manufacturers and publications in scientific journals. Results MediCAD, TraumaCAD, Surgimap, Sectra AB and OrthoView are most common DSSs used for spine and hip surgery planning. The above systems can be applied in orthopedic surgery of several independent anatomical regions (e.g., spine, pelvis, femur, tibia, foot). But none of the systems can be applied to spine-pelvic complex. DSS facilitates only geometrical planning with geometric measurements, simulation of physiologically normal location of anatomical elements as well as selection and semi-automatic implant positioning. Conclusion Both geometrical planning and biomechanical simulation are required to achieve positive long-term follow-up of surgical treatment. Biomechanical simulation allows assessment of an extent and pattern of injury caused by malalignment of spine-pelvic complex and surgical intervention planning with the help of reconstruction options offered. The use of DSS should involve geometric planning, biomechanical simulation of the expected surgical outcome and prediction of a long-term follow-up. Introduction of DSS into clinical practice will facilitate the quality of medical care and rehabilitation with concurrent optimization of the national expenditure on health care.

The role of the nuclear lamina (NL) in chromatin architecture is still poorly understood. Here, the authors provide evidence that disruption of the NL in Drosophila cells leads to overall chromatin compaction and repositioning from the nuclear envelope, whereas lamina-associated regions become less compacted and transcription within them is increased.

Enamel is the hardest substance in the human body and contains the highest percentage of minerals (96%), with water and organic material composing the rest. The objective: to improve the quality of carious dental cavities filling in patients by determining the regularities of enamel prisms direction and quality of “enamel-filling”connection in topographically different parts of permanent human canines crown. Materials and methods. 40 permamnnet canines with intact enamel, removed because of trauma or orthodontic indications; 89 caries patients. Results. Angulation and direction of enamel prisms in different parts, surfaces and layers of a human permanent canines has been revealed. Conclusions. Features of different parts of enamel prisms inclination in toporgathically different parts of a human permanent canines has been shown. It has been revealed that the efficiency of a filling and enamel coalescence depends on the prevailing direction of enamel prisms in different parts of canine crown. Taking into account the peculiarities of enamel prisms location in the tooth crown at carious cavity preparation, increases the effectiveness of secondary caries prevention.

We present the results of U-Pb zircon dating conducted using laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS), isotopic tracing analyses of Hf in zircon and Sr-Nd in whole-rock and whole-rock major oxides, and trace element abundances of 12 plutonic and volcanic rocks present on the Antarctic Peninsula. The dataset is presented in combination with the results of previous studies conducted in both Patagonia and the Antarctic Peninsula. These results were filtered for concordant 206Pb–238U zircon ages and topology of the 40Ar/39Ar age spectra. These results may be useful for researchers studying the geological evolution of southern Gondwana, West Antarctica or Patagonia. The interpretation of this dataset is found in the co-submitted paper by Bastias, et al. (2021a) titled ‘A revised interpretation of the Chon Aike magmatic province: active margin origin and implications for the opening of the Weddell Sea’.

The cell nucleus is frequently considered a cage in which the genome is placed to protect it from various external factors. Inside the nucleus, many functional compartments have been identified that are directly or indirectly involved in implementing genomic DNA’s genetic functions. For many years, it was assumed that these compartments are assembled on a proteinaceous scaffold (nuclear matrix), which provides a structural milieu for nuclear compartmentalization and genome folding while simultaneously offering some rigidity to the cell nucleus. The results of research in recent years have made it possible to consider the cell nucleus from a different angle. From the “box” in which the genome is placed, the nucleus has become a kind of mobile exoskeleton, which is formed around the packaged genome, under the influence of transcription and other processes directly related to the genome activity. In this review, we summarize the main arguments in favor of this point of view by analyzing the mechanisms that mediate cell nucleus assembly and support its resistance to mechanical stresses.

En América Latina más de 100 millones de personas no tienen acceso a una energía limpia, asequible y constante. En Colombia, esto sucede en las denominadas Zonas No- Interconectadas - ZNI con una población de más de 2 millones de personas, que viven en regiones con abundantes y diversos recursos energéticos renovables. En este artículo se presenta una metodología para el diseño de microrredes en zonas aisladas, partiendo de la evaluación de recursos energéticos renovables locales. Una microrred es un sistema que usa varias fuentes y utiliza tecnologías de conversión de energías renovables en electricidad para proveer de electricidad zonas asiladas. Estas “microrredes” inteligentes consisten en un sistema energético que integra la generación, transmisión, distribución y uso final de la energía, de manera eficiente y amigable con el medio ambiente, y con un mínimo impacto socio-cultural, permitiendo el intercambio de información entre todos los componentes del sistema para un óptimo control. Por ello, es de suma importancia desarrollar un acertado análisis y evaluación de recursos energéticos, con el objetivo de optimizar al máximo el diseño de microrredes

New effective dynamic models for motion of polymeric film have been proposed in the paper. These models in contrast to known ones take in to account deformation processes which occur at a unit for polymer-film materials production. It has been shown that the deformation process of a polуmer film in intersectional area determined by its tension depends on ratio of linear section velocities and tension and deformation values in these sections. An analysis of the proposed dynamic models of polymer film motion has shown that a decrease in its deformations in every zone of the unit can be achieved both by changing ratio of input and output velocities and introducing a compensator for perturbing influences due to deformations of the film at the entrance to the zone. Possible channels for automatic control of the unit for polymer-film material production have been identified with the aim of improving quality of products. While using the proposed dynamic models it has been demonstrated that it is necessary to apply systems for automatic measuring of section rotation speed and film tension in the unit for polymer-film material production in order to ensure effective control over an extrusion process. The proposed dynamic model can be efficiently used to create an adaptive system which is applied to control a multi-motor drive of the unit for of polymer-film material production.

Background. Nowadays it is being reported an increased number of cases of generalization of odontogenic infections which are caused by dental caries, periodontal diseases and other oral diseases. The beginning and progression of diseases depend on individual genetic profile of patient, but data about the role of genetic factors in purulent-inflammatory diseases of maxillofacial area pathogenesis are limited now. The aim of this study was to assess the possible association between IL-1β, IL-8, IL-10 and VEGF polymorphisms and risk of odontogenic maxillofacial infections. Materials and methods 80 patients with odontogenic maxillofacial infection (with and without diabetes mellitus) and 20 donors were examined. All patients’ with odontogenic maxillofacial infection groups were operated and received antibiotic and detoxification therapy. Polymorphism in IL-1B +3954C/T (rs1143634), IL-8 -251T/A (rs4073), IL-10 -1082G/A (rs1800896) and VEGF -634 G/C (rs 2010963) were assessed by polymerase chain reaction. Odds ratio (OR) with 95% confidence interval (CI), Chi-square test were used for statistical analyses. Results. No association observed between VEGF -634 G/C polymorphism and risk of odontogenic maxillofacial infections in patient without diabetes mellitus using all the genetic models. In patients with diabetes mellitus observed association between VEGF -634 G/C polymorphism and odontogenic maxillofacial infections in the codominant (OR=0,429, 95%СІ 0,185-0,994, р=0,046), heterozygous (OR=0,167, 95%СІ 0,048-0,574, р=0,004)and recessive (OR=0,194, 95%СІ 0,061-0,619, р=0,005) models. Polimorphism IL-1B +3954C/T increased the risk of odontogenic maxillofacial infections in patient without diabetes mellitus in the codominant (OR=0,059, 95%СІ 0,023-0,151, р

Abstract In mammals, genomic DNA that is roughly 2 m long is folded to fit the size of the cell nucleus that has a diameter of about 10 μm. The folding of genomic DNA is mediated via assembly of DNA-protein complex, chromatin. In addition to the reduction of genomic DNA linear dimensions, the assembly of chromatin allows to discriminate and to mark active (transcribed) and repressed (non-transcribed) genes. Consequently, epigenetic regulation of gene expression occurs at the level of DNA packaging in chromatin. Taking into account the increasing attention of scientific community toward epigenetic systems of gene regulation, it is very important to understand how DNA folding in chromatin is related to gene activity. For many years the hierarchical model of DNA folding was the most popular. It was assumed that nucleosome fiber (10-nm fiber) is folded into 30-nm fiber and further on into chromatin loops attached to a nuclear/chromosome scaffold. Recent studies have demonstrated that there is much less regularity in chromatin folding within the cell nucleus. The very existence of 30-nm chromatin fibers in living cells was questioned. On the other hand, it was found that chromosomes are partitioned into self-interacting spatial domains that restrict the area of enhancers action. Thus, TADs can be considered as structural-functional domains of the chromosomes. Here we discuss the modern view of DNA packaging within the cell nucleus in relation to the regulation of gene expression. Special attention is paid to the possible mechanisms of the chromatin fiber self-assembly into TADs. We discuss the model postulating that partitioning of the chromosome into TADs is determined by the distribution of active and inactive chromatin segments along the chromosome. This article was specially invited by the editors and represents work by leading researchers.

Abstract Background In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results in dramatic upregulation of alpha-globin genes making their expression comparable to the rRNA transcriptional output. Little is known about the influence of the erythroid-specific alpha-globin gene transcription outburst on adjacent, widely expressed genes and large-scale chromatin organization. Here, we have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured lymphoid cells and cultured erythroid cells before and after induction of terminal erythroid differentiation. Results We found that, similarly to mammalian genome, the chicken genomes is organized in TADs and compartments. Full activation of the alpha-globin gene transcription in differentiated erythroid cells is correlated with upregulation of several adjacent housekeeping genes and the emergence of abundant intergenic transcription. An extended chromosome region encompassing the alpha-globin cluster becomes significantly decompacted in differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the upstream major regulatory element (MRE) becomes highly enriched with chromatin interactions as compared to lymphoid and proliferating erythroid cells. The alpha-globin gene domain and the neighboring loci reside within the A-like chromatin compartment in both lymphoid and erythroid cells and become further segregated from the upstream gene desert upon terminal erythroid differentiation. Conclusions Our findings demonstrate that the effects of tissue-specific transcription activation are not restricted to the host genomic locus but affect the overall chromatin structure and transcriptional output of the encompassing topologically associating domain.

Exon skipping is a promising strategy for Duchenne muscular dystrophy (DMD) disease-modifying therapy. To make this approach safe, ensuring that excluding one or more exons will restore the reading frame and that the resulting protein will retain critical functions of the full-length dystrophin protein is necessary. However, in vivo testing of the consequences of skipping exons that encode the N-terminal actin-binding domain (ABD) has been confounded by the absence of a relevant animal model. We created a mouse model of the disease recapitulating a novel human mutation, a large de novo deletion of exons 8-34 of the DMD gene, found in a Russian DMD patient. This mutation was achieved by deleting exons 8-34 of the X-linked mouse Dmd gene using CRISPR/Cas9 genome editing, which led to a reading frame shift and the absence of functional dystrophin production. Male mice carrying this deletion display several important signs of muscular dystrophy, including a gradual age-dependent decrease in muscle strength, increased creatine kinase, muscle fibrosis and central nucleation. The degrees of these changes are comparable to those observed in mdx mice, a standard laboratory model of DMD. This new model of DMD will be useful for validating therapies based on skipping exons that encode the N-terminal ABD and for improving our understanding of the role of the N-terminal domain and central rod domain in the biological function of dystrophin. Simultaneous skipping of exons 6 and 7 should restore the gene reading frame and lead to the production of a protein that might retain functionality despite the partial deletion of the ABD.

Enamel is the hardest substance in the human body and contains the highest percentage of minerals (96%), with water and organic material composing the rest. The objective: to improve the quality of carious dental cavities filling in patients by determining the regularities of enamel prisms direction and quality of “enamel-filling”connection in topographically different parts of permanent human canines crown. Materials and methods. 40 permamnnet canines with intact enamel, removed because of trauma or orthodontic indications; 89 caries patients. Results. Angulation and direction of enamel prisms in different parts, surfaces and layers of a human permanent canines has been revealed. Conclusions. Features of different parts of enamel prisms inclination in toporgathically different parts of a human permanent canines has been shown. It has been revealed that the efficiency of a filling and enamel coalescence depends on the prevailing direction of enamel prisms in different parts of canine crown. Taking into account the peculiarities of enamel prisms location in the tooth crown at carious cavity preparation, increases the effectiveness of secondary caries prevention.

Haptic sound symbolism has been found in adults, between ideophones and various textures, between words and shape, and between written words and texture. However, associations between the sound of nonwords and features other than shape and in early stages of development have been less explored. The present study investigates the haptic manifestation of sound symbolism in an early developmental stage. We examined associations between nonwords and the rough-smooth tactile dimension in 3.5-to-4.5-year-old children. Two experiments were conducted: a pointing selection task and a naming task. Sound symbolic associations were found in the naming task, but not in the pointing task. On the other hand an unexpected bias towards smoothness was found in the pointing task. We explain these results by suggesting that the articulation of nonwords may facilitate or intensify sound symbolism, and that hedonic biases are manifested in the pointing task.

The relevance of the article consists in the most frequent use of computer-aided information systems in all human sectors, including building management. These measures implementation may entail more efficient resource use and make citizens lives easier and better. The study seeks to develop a model for computer-aided project managing residential complexes and business centers based on digital technologies. For this reason, the following tasks were completed: we studied the theoretical issues of computer- aided real estate management; defined the product requirements from the perspective management company; analyzed the usefulness of introducing a product for a management company; evaluated the economic efficiency. We have identified solutions that help save and optimize the use of resources. Under this study we identified the solutions enforcing careful and optimized use of resources.