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The purpose of the study is to identify the features of ensuring the competitiveness of distance business education and modern trends in the development of the field of educational services and the role of digital technologies and project management in these processes. General scientific and special methods are used: historical-logical grouping (systematization of electronic learning system elements, distance education, approaches of project management etc.); generalization (understanding of modern role and evaluation of distance education and e-learning resources, digitalization processes). It has been proven that such an alternative to traditional formal education is more closely correlated with the demands of the labour market, allows to better and more quickly meet the needs of employers, and for employees to ensure their professional development throughout their life and to apply their competencies in the countries of the European Union. Approaches to project management in distance business education are described. It has been established that project management in business education has a scientific basis based on pedagogical theories and researches, which supports active, collaborative and critical learning, and also promotes the development of skills that are important in today's information society and the labour market., El propósito del estudio es identificar las características que garantizan la competitividad de la educación empresarial a distancia y las tendencias modernas en el desarrollo del campo de los servicios educativos y el papel de las tecnologías digitales y la gestión de proyectos en estos procesos. Se utilizan métodos científicos generales y especiales: agrupación histórico-lógica (sistematización de elementos de sistemas de aprendizaje electrónico, educación a distancia, enfoques de gestión de proyectos, etc.); generalización (comprensión del papel moderno y evaluación de la educación a distancia y los recursos de e-learning, procesos de digitalización). Se ha demostrado que una alternativa de este tipo a la educación formal tradicional está más estrechamente correlacionada con las demandas del mercado laboral, permite satisfacer mejor y más rápidamente las necesidades de los empleadores y que los empleados garanticen su desarrollo profesional a lo largo de su vida y apliquen sus competencias en los países de la Unión Europea. Se describen enfoques para la gestión de proyectos en la educación empresarial a distancia. Se ha establecido que la gestión de proyectos en la educación empresarial tiene una base científica basada en teorías e investigaciones pedagógicas, que apoya el aprendizaje activo, colaborativo y crítico, y también promueve el desarrollo de habilidades importantes en la sociedad de la información y el mercado laboral actual.

Background Neuroblastoma (NB) is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. It is a complex disease that can result in diverse clinical outcomes. In some children, tumors regress spontaneously. Others respond well to existing treatments. But for the high-risk group, which constitutes approximately 40% of all patients, the prognosis remains dire despite collaborative efforts in basic and clinical research. While its exact cellular origin is still under debate, NB is assumed to arise from the neural crest cell lineage including multipotent Schwann cell precursors (SCPs), which differentiate into sympatho-adrenal cell states eventually producing chromaffin cells and sympathoblasts. Methods To investigate clonal development of neuroblastoma cell states, we performed haplotype-specific analysis of human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Samples were also assessed using immunofluorescence stainings and fluorescence in-situ hybridization (FISH). Results Beyond adrenergic tumor cells, we identify subpopulations of aneuploid SCP-like cells, characterized by clonal expansion, whole-chromosome 17 gains, as well as expression programs of proliferation, apoptosis, and a non-immunomodulatory phenotype. Conclusion Aneuploid pre-malignant SCP-like cells represent a novel feature of NB. Genetic evidence and tumor phylogeny suggest that these clones and malignant adrenergic populations originate from aneuploidy-prone cells of migrating neural crest or SCP origin, before lineage commitment to sympatho-adrenal cell states. Our findings expand the phenotypic spectrum of NB cell states. Considering the multipotency of SCPs in development, we suggest that the transformation of fetal SCPs may represent one possible mechanism of tumor initiation in NB with chromosome 17 aberrations as a characteristic element., De tre första författarna delar förstaförfattarskapet

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Background Neuroblastoma (NB) is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. It is a complex disease that can result in diverse clinical outcomes. In some children, tumors regress spontaneously. Others respond well to existing treatments. But for the high-risk group, which constitutes approximately 40% of all patients, the prognosis remains dire despite collaborative efforts in basic and clinical research. While its exact cellular origin is still under debate, NB is assumed to arise from the neural crest cell lineage including multipotent Schwann cell precursors (SCPs), which differentiate into sympatho-adrenal cell states eventually producing chromaffin cells and sympathoblasts. Methods To investigate clonal development of neuroblastoma cell states, we performed haplotype-specific analysis of human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Samples were also assessed using immunofluorescence stainings and fluorescence in-situ hybridization (FISH). Results Beyond adrenergic tumor cells, we identify subpopulations of aneuploid SCP-like cells, characterized by clonal expansion, whole-chromosome 17 gains, as well as expression programs of proliferation, apoptosis, and a non-immunomodulatory phenotype. Conclusion Aneuploid pre-malignant SCP-like cells represent a novel feature of NB. Genetic evidence and tumor phylogeny suggest that these clones and malignant adrenergic populations originate from aneuploidy-prone cells of migrating neural crest or SCP origin, before lineage commitment to sympatho-adrenal cell states. Our findings expand the phenotypic spectrum of NB cell states. Considering the multipotency of SCPs in development, we suggest that the transformation of fetal SCPs may represent one possible mechanism of tumor initiation in NB with chromosome 17 aberrations as a characteristic element., De tre första författarna delar förstaförfattarskapet

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Background Neuroblastoma (NB) is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. It is a complex disease that can result in diverse clinical outcomes. In some children, tumors regress spontaneously. Others respond well to existing treatments. But for the high-risk group, which constitutes approximately 40% of all patients, the prognosis remains dire despite collaborative efforts in basic and clinical research. While its exact cellular origin is still under debate, NB is assumed to arise from the neural crest cell lineage including multipotent Schwann cell precursors (SCPs), which differentiate into sympatho-adrenal cell states eventually producing chromaffin cells and sympathoblasts. Methods To investigate clonal development of neuroblastoma cell states, we performed haplotype-specific analysis of human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Samples were also assessed using immunofluorescence stainings and fluorescence in-situ hybridization (FISH). Results Beyond adrenergic tumor cells, we identify subpopulations of aneuploid SCP-like cells, characterized by clonal expansion, whole-chromosome 17 gains, as well as expression programs of proliferation, apoptosis, and a non-immunomodulatory phenotype. Conclusion Aneuploid pre-malignant SCP-like cells represent a novel feature of NB. Genetic evidence and tumor phylogeny suggest that these clones and malignant adrenergic populations originate from aneuploidy-prone cells of migrating neural crest or SCP origin, before lineage commitment to sympatho-adrenal cell states. Our findings expand the phenotypic spectrum of NB cell states. Considering the multipotency of SCPs in development, we suggest that the transformation of fetal SCPs may represent one possible mechanism of tumor initiation in NB with chromosome 17 aberrations as a characteristic element., De tre första författarna delar förstaförfattarskapet

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Background Neuroblastoma (NB) is a heterogeneous embryonal malignancy and the deadliest tumor of infancy. It is a complex disease that can result in diverse clinical outcomes. In some children, tumors regress spontaneously. Others respond well to existing treatments. But for the high-risk group, which constitutes approximately 40% of all patients, the prognosis remains dire despite collaborative efforts in basic and clinical research. While its exact cellular origin is still under debate, NB is assumed to arise from the neural crest cell lineage including multipotent Schwann cell precursors (SCPs), which differentiate into sympatho-adrenal cell states eventually producing chromaffin cells and sympathoblasts. Methods To investigate clonal development of neuroblastoma cell states, we performed haplotype-specific analysis of human tumor samples using single-cell multi-omics, including joint DNA/RNA sequencing of sorted single cells (DNTR-seq). Samples were also assessed using immunofluorescence stainings and fluorescence in-situ hybridization (FISH). Results Beyond adrenergic tumor cells, we identify subpopulations of aneuploid SCP-like cells, characterized by clonal expansion, whole-chromosome 17 gains, as well as expression programs of proliferation, apoptosis, and a non-immunomodulatory phenotype. Conclusion Aneuploid pre-malignant SCP-like cells represent a novel feature of NB. Genetic evidence and tumor phylogeny suggest that these clones and malignant adrenergic populations originate from aneuploidy-prone cells of migrating neural crest or SCP origin, before lineage commitment to sympatho-adrenal cell states. Our findings expand the phenotypic spectrum of NB cell states. Considering the multipotency of SCPs in development, we suggest that the transformation of fetal SCPs may represent one possible mechanism of tumor initiation in NB with chromosome 17 aberrations as a characteristic element., De tre första författarna delar förstaförfattarskapet

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions., Article; Export Date: 20 March 2024; Cited By: 0; Correspondence Address: P.A. Andersson; Department of Behavioral Sciences and Learning, Linköping University, Linköping, 581 83, Sweden; email: per.a.andersson@liu.se

The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat. Tightness-looseness theory predicts that social norms strengthen following threat. Here the authors test this and find that, after the emergence of the COVID-19 pandemic, hand washing norms increased, but no evidence was observed for a robust change in most other norms.

The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat. Tightness-looseness theory predicts that social norms strengthen following threat. Here the authors test this and find that, after the emergence of the COVID-19 pandemic, hand washing norms increased, but no evidence was observed for a robust change in most other norms., Funding Agencies|Knut and Wallenberg Grant "How do human norms form and change?" [870827]; Swedish Research Council grant "Norms & Risk: Do social norms help dealing with collective threats" [2021-06271]; Ministero dell'Istruzione dell'Universita e della Ricerca, PRIN 2017 [20178TRM3F]; Universidad de Los Andes; Fondo Vicerrectoria de Investigaciones; Ministry of Innovation and Technology of Hungary; National Research, Development and Innovation Fund [NKFIH-OTKA K135963]; Czech Science Foundation [23-061770 S]; Institute of Psychology, Czech Academy of Sciences [RVO: 68081740]; Netherlands Organisation for Scientific Research, VI.Veni; RA Science Committee; European Commission, Horizon 2020 [PID2022-141802NB-I00]; Open University of Israel; UKRI Grant "Secret Power"; HSE University Basic Research Program; European Commission's "European Research Council - STG" Scheme [W911NF-19-1-910281]; MCIN/AEI; ERDF A way of making Europe; US Army Research Office [2016.0167]; Netherlands Organisation for Scientific Research; [511687]; [EP/X02170X/1]; [20TTSH-070]; [019.183SG.001]; [201 G.013]

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions., Funding Agencies|Swedish Foundation for Humanities and Social Sciences (Riksbankens Jubileumsfond) [P17-0030:1]; CAS Youth Innovation Promotion Association; Institute of Psychology, Chinese Academy of Sciences [Y5CX052003, E2CX3315CX]; Czech Science Foundation [23-061770S]; Institute of Psychology, Czech Academy of Sciences [RVO: 68081740]

In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in <10 h. We successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.

The purpose of the study is to identify the features of ensuring the competitiveness of distance business education and modern trends in the development of the field of educational services and the role of digital technologies and project management in these processes. General scientific and special methods are used: historical-logical grouping (systematization of electronic learning system elements, distance education, approaches of project management etc.); generalization (understanding of modern role and evaluation of distance education and e-learning resources, digitalization processes). It has been proven that such an alternative to traditional formal education is more closely correlated with the demands of the labour market, allows to better and more quickly meet the needs of employers, and for employees to ensure their professional development throughout their life and to apply their competencies in the countries of the European Union. Approaches to project management in distance business education are described. It has been established that project management in business education has a scientific basis based on pedagogical theories and researches, which supports active, collaborative and critical learning, and also promotes the development of skills that are important in today's information society and the labour market., El propósito del estudio es identificar las características que garantizan la competitividad de la educación empresarial a distancia y las tendencias modernas en el desarrollo del campo de los servicios educativos y el papel de las tecnologías digitales y la gestión de proyectos en estos procesos. Se utilizan métodos científicos generales y especiales: agrupación histórico-lógica (sistematización de elementos de sistemas de aprendizaje electrónico, educación a distancia, enfoques de gestión de proyectos, etc.); generalización (comprensión del papel moderno y evaluación de la educación a distancia y los recursos de e-learning, procesos de digitalización). Se ha demostrado que una alternativa de este tipo a la educación formal tradicional está más estrechamente correlacionada con las demandas del mercado laboral, permite satisfacer mejor y más rápidamente las necesidades de los empleadores y que los empleados garanticen su desarrollo profesional a lo largo de su vida y apliquen sus competencias en los países de la Unión Europea. Se describen enfoques para la gestión de proyectos en la educación empresarial a distancia. Se ha establecido que la gestión de proyectos en la educación empresarial tiene una base científica basada en teorías e investigaciones pedagógicas, que apoya el aprendizaje activo, colaborativo y crítico, y también promueve el desarrollo de habilidades importantes en la sociedad de la información y el mercado laboral actual.

The purpose of the study is to identify the features of ensuring the competitiveness of distance business education and modern trends in the development of the field of educational services and the role of digital technologies and project management in these processes. General scientific and special methods are used: historical-logical grouping (systematization of electronic learning system elements, distance education, approaches of project management etc.); generalization (understanding of modern role and evaluation of distance education and e-learning resources, digitalization processes). It has been proven that such an alternative to traditional formal education is more closely correlated with the demands of the labour market, allows to better and more quickly meet the needs of employers, and for employees to ensure their professional development throughout their life and to apply their competencies in the countries of the European Union. Approaches to project management in distance business education are described. It has been established that project management in business education has a scientific basis based on pedagogical theories and researches, which supports active, collaborative and critical learning, and also promotes the development of skills that are important in today's information society and the labour market., El propósito del estudio es identificar las características que garantizan la competitividad de la educación empresarial a distancia y las tendencias modernas en el desarrollo del campo de los servicios educativos y el papel de las tecnologías digitales y la gestión de proyectos en estos procesos. Se utilizan métodos científicos generales y especiales: agrupación histórico-lógica (sistematización de elementos de sistemas de aprendizaje electrónico, educación a distancia, enfoques de gestión de proyectos, etc.); generalización (comprensión del papel moderno y evaluación de la educación a distancia y los recursos de e-learning, procesos de digitalización). Se ha demostrado que una alternativa de este tipo a la educación formal tradicional está más estrechamente correlacionada con las demandas del mercado laboral, permite satisfacer mejor y más rápidamente las necesidades de los empleadores y que los empleados garanticen su desarrollo profesional a lo largo de su vida y apliquen sus competencias en los países de la Unión Europea. Se describen enfoques para la gestión de proyectos en la educación empresarial a distancia. Se ha establecido que la gestión de proyectos en la educación empresarial tiene una base científica basada en teorías e investigaciones pedagógicas, que apoya el aprendizaje activo, colaborativo y crítico, y también promueve el desarrollo de habilidades importantes en la sociedad de la información y el mercado laboral actual.

In a previous paper using Gaia DR2 data, we demonstrated that the two closely situated open clusters Collinder 135 and UBC 7 might have formed together about 50 Myr ago. In this work, we performed star-by-star dynamical modelling of the evolution of the open clusters Collinder 135 and UBC 7 from their supposed initial state to their present-day state, reproducing observational distributions of members. Modelling of the Collinder 135 and UBC 7 dynamical evolution was done using the high-order parallel N-body code \phi-GPU with up-to-date stellar evolution. Membership and characteristics of the clusters were acquired based on Gaia DR3 data. The comparison of the present-day radial cumulative star count obtained from the N-body simulations with the current observational data gave us full consistency of the model with observational data, especially in the central 8 pc, where 80% of the stars reside. The proper motion velocity components obtained from the N-body simulations of the stars are also quite consistent with the observed distributions and error bars. These results show that our numerical modelling is able to reproduce the open clusters' current complex 6D observed phase-space distributions with a high level of confidence. Thus, the model demonstrates that the hypothesis of a common origin of Collinder 135 and UBC 7 complies with present-day observational data., Comment: Astronomy & Astrophysics, accepted

When someone violates a social norm, others may think that some sanction would be appropriate. We examine how the experience of emotions like anger and disgust relate to the judged appropriateness of sanctions, in a pre-registered analysis of data from a large-scale study in 56 societies. Across the world, we find that individuals who experience anger and disgust over a norm violation are more likely to endorse confrontation, ostracism and, to a smaller extent, gossip. Moreover, we find that the experience of anger is consistently the strongest predictor of judgments of confrontation, compared to other emotions. Although the link between state-based emotions and judgments may seem universal, its strength varies across countries. Aligned with theoretical predictions, this link is stronger in societies, and among individuals, that place higher value on individual autonomy. Thus, autonomy values may increase the role that emotions play in guiding judgments of social sanctions.

Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.

Schizophrenia is one of the most widespread and complex mental disorders. To characterize the impact of schizophrenia, we performed single-nucleus RNA sequencing (snRNA-seq) of >220,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls. In addition, >115,000 neurons were analyzed topographically by immunohistochemistry. Compositional analysis of snRNA-seq data revealed a reduction in abundance of GABAergic neurons and a concomitant increase in principal neurons, most pronounced for upper cortical layer subtypes, which was substantiated by histological analysis. Many neuronal subtypes showed extensive transcriptomic changes, the most marked in upper-layer GABAergic neurons, including down-regulation in energy metabolism and up-regulation in neurotransmission. Transcription factor network analysis demonstrated a developmental origin of transcriptomic changes. Last, Visium spatial transcriptomics further corroborated upper-layer neuron vulnerability in schizophrenia. Overall, our results point toward general network impairment within upper cortical layers as a core substrate associated with schizophrenia symptomatology.

Single-molecule spatial transcriptomics protocols based on in situ sequencing or multiplexed RNA fluorescent hybridization can reveal detailed tissue organization. However, distinguishing the boundaries of individual cells in such data is challenging and can hamper downstream analysis. Current methods generally approximate cells positions using nuclei stains. We describe a segmentation method, Baysor, that optimizes two-dimensional (2D) or three-dimensional (3D) cell boundaries considering joint likelihood of transcriptional composition and cell morphology. While Baysor can take into account segmentation based on co-stains, it can also perform segmentation based on the detected transcripts alone. To evaluate performance, we extend multiplexed error-robust fluorescence in situ hybridization (MERFISH) to incorporate immunostaining of cell boundaries. Using this and other benchmarks, we show that Baysor segmentation can, in some cases, nearly double the number of cells compared to existing tools while reducing segmentation artifacts. We demonstrate that Baysor performs well on data acquired using five different protocols, making it a useful general tool for analysis of imaging-based spatial transcriptomics.

Carbon fibres used as a honeycomb core material (subject to a proper in-depth analysis of their reinforcement patterns) allows solving the thermo-dimensional stability problem of the units for space systems. Based on the results of numerical simulations with the support of finite element analysis, the paper provides an evaluation of the accuracy of analytical dependencies for the determination of the moduli of elasticity of a carbon fibre honeycomb core in tension/compression and shear. It is shown that a carbon fibre honeycomb reinforcement pattern has a significant impact on the mechanical performance of the carbon fibre honeycomb core. For example, for honeycombs measuring 10 mm in height, the maximum shear modulus values corresponding to the reinforcement pattern of +/- 45 degrees exceed the minimum values for a reinforcement pattern of 0 degrees and 90 degrees by more than 5 times in the XOZ plane and 4 times for the shear modulus in the YOZ plane. The maximum modulus of the elasticity of the honeycomb core in the transverse tension, corresponding to a reinforcement pattern of +/- 75 degrees, exceeds the minimum modulus for the reinforcement pattern of +/- 15 degrees more than 3 times. We observe a decrease in the values of the mechanical performance of the carbon fibre honeycomb core depending on its height. With a honeycomb reinforcement pattern of +/- 45 degrees, the decrease in the shear modulus is 10% in the XOZ plane and 15% in the YOZ plane. The reduction in the modulus of elasticity in the transverse tension for the reinforcement pattern does not exceed 5%. It is shown that in order to ensure high-level moduli of elasticity with respect to tension/compression and shear at the same time, it is necessary to focus on a reinforcement pattern of +/- 64 degrees. The paper covers the development of the experimental prototype technology that produces carbon fibre honeycomb cores and structures for aerospace applications. It is shown by experiments that the use

Carbon fibres used as a honeycomb core material (subject to a proper in-depth analysis of their reinforcement patterns) allows solving the thermo-dimensional stability problem of the units for space systems. Based on the results of numerical simulations with the support of finite element analysis, the paper provides an evaluation of the accuracy of analytical dependencies for the determination of the moduli of elasticity of a carbon fibre honeycomb core in tension/compression and shear. It is shown that a carbon fibre honeycomb reinforcement pattern has a significant impact on the mechanical performance of the carbon fibre honeycomb core. For example, for honeycombs measuring 10 mm in height, the maximum shear modulus values corresponding to the reinforcement pattern of +/- 45 degrees exceed the minimum values for a reinforcement pattern of 0 degrees and 90 degrees by more than 5 times in the XOZ plane and 4 times for the shear modulus in the YOZ plane. The maximum modulus of the elasticity of the honeycomb core in the transverse tension, corresponding to a reinforcement pattern of +/- 75 degrees, exceeds the minimum modulus for the reinforcement pattern of +/- 15 degrees more than 3 times. We observe a decrease in the values of the mechanical performance of the carbon fibre honeycomb core depending on its height. With a honeycomb reinforcement pattern of +/- 45 degrees, the decrease in the shear modulus is 10% in the XOZ plane and 15% in the YOZ plane. The reduction in the modulus of elasticity in the transverse tension for the reinforcement pattern does not exceed 5%. It is shown that in order to ensure high-level moduli of elasticity with respect to tension/compression and shear at the same time, it is necessary to focus on a reinforcement pattern of +/- 64 degrees. The paper covers the development of the experimental prototype technology that produces carbon fibre honeycomb cores and structures for aerospace applications. It is shown by experiments that the use

The purpose of the study is to conceptualize the phenomenon of vergence of technologies and innovations in the context of building a society as a complex system by modernizing the innovation environment. To achieve the goal, general scientific and special-scientific methods of cognition were used, in particular, dialectical, formal-logical, analysis and synthesis, system-structural. The key methodological principles, spatial-topological and ontological, were presented. It is confirmed that the concept of "vergence" is the state of systems at the point of intersection of divergent and convergent processes, as well as their balancing. Vergence as a method of creative thinking was used in this study primarily to solve problems and tasks related to the synchronism of various contradictory processes (reconciles the processes of "scattering", "acceleration" and "gathering", "braking"). The value of this approach was in finding multiple solutions to ambiguous problems. The results of the study confirmed that the vergent interaction of technologies and innovations, the merging of funds and resources that contribute to the modernization of the innovation space, their analysis and synchronism, excluded the position of rest in the social system and, on the contrary, gave rise to a situation of accelerated but controlled dynamism., El propósito del estudio es conceptualizar el fenómeno de convergencia de tecnologías e innovaciones en el contexto de la construcción de una sociedad como un sistema complejo mediante la modernización del entorno de innovación. Para lograr el objetivo, se utilizaron métodos de cognición científicos generales y científicos especiales, en particular: dialéctico, lógico-formal, análisis y síntesis, sistema-estructural. Se confirma que el concepto de "vergencia" es el estado de los sistemas en el punto de intersección de procesos divergentes y convergentes, así como su equilibrio. La vergencia como método de pensamiento creativo se utilizó en este estudio principalmente para resolver problemas y tareas relacionadas con el sincronismo de varios procesos contradictorios (reconcilia los procesos de "dispersión", "aceleración" y "reunión", "frenado"). El valor de este enfoque reside en encontrar múltiples soluciones a problemas ambiguos. Los resultados del estudio confirmaron que la interacción vergente de tecnologías e innovaciones, la fusión de fondos y recursos que contribuyen a la modernización del espacio de innovación, su análisis y sincronismo, excluyeron la posición de reposo en el sistema social y, por el contrario, dio lugar a una situación de dinamismo acelerado pero controlado.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Post-Summit Results, Delegates' Summit, September 11, 2023, The (12+1)th Symposium on Advanced Computation and Information in Natural and Applied Sciences (SACINAS), The 21th International Conference of Numerical Analysis and Applied Mathematics (ICNAAM), September 11-17, 2023, Heraklion, Crete, Greece

In this research, digital technologies that will potentially be useful for teachers in an inclusive educational space were considered. The combined classification of digital technologies of inclusive direction, including software and hardware in three main areas, is offered: for training and repetition; to help with learning; and to expand learning opportunities. The authors developed and theoretically substantiated a model for preparing pre-service teachers to use digital technologies in an inclusive educational space. The effectiveness of the developed model was tested through a pedagogical experiment that involved three tests based on criteria. The effectiveness of the authors’ model was confirmed by the sign test at the significance level of 0.05.

In this research, digital technologies that will potentially be useful for teachers in an inclusive educational space were considered. The combined classification of digital technologies of inclusive direction, including software and hardware in three main areas, is offered: for training and repetition; to help with learning; and to expand learning opportunities. The authors developed and theoretically substantiated a model for preparing pre-service teachers to use digital technologies in an inclusive educational space. The effectiveness of the developed model was tested through a pedagogical experiment that involved three tests based on criteria. The effectiveness of the authors’ model was confirmed by the sign test at the significance level of 0.05.

The purpose of the study is to conceptualize the phenomenon of vergence of technologies and innovations in the context of building a society as a complex system by modernizing the innovation environment. To achieve the goal, general scientific and special-scientific methods of cognition were used, in particular, dialectical, formal-logical, analysis and synthesis, system-structural. The key methodological principles, spatial-topological and ontological, were presented. It is confirmed that the concept of "vergence" is the state of systems at the point of intersection of divergent and convergent processes, as well as their balancing. Vergence as a method of creative thinking was used in this study primarily to solve problems and tasks related to the synchronism of various contradictory processes (reconciles the processes of "scattering", "acceleration" and "gathering", "braking"). The value of this approach was in finding multiple solutions to ambiguous problems. The results of the study confirmed that the vergent interaction of technologies and innovations, the merging of funds and resources that contribute to the modernization of the innovation space, their analysis and synchronism, excluded the position of rest in the social system and, on the contrary, gave rise to a situation of accelerated but controlled dynamism., El propósito del estudio es conceptualizar el fenómeno de convergencia de tecnologías e innovaciones en el contexto de la construcción de una sociedad como un sistema complejo mediante la modernización del entorno de innovación. Para lograr el objetivo, se utilizaron métodos de cognición científicos generales y científicos especiales, en particular: dialéctico, lógico-formal, análisis y síntesis, sistema-estructural. Se confirma que el concepto de "vergencia" es el estado de los sistemas en el punto de intersección de procesos divergentes y convergentes, así como su equilibrio. La vergencia como método de pensamiento creativo se utilizó en este estudio principalmente para resolver problemas y tareas relacionadas con el sincronismo de varios procesos contradictorios (reconcilia los procesos de "dispersión", "aceleración" y "reunión", "frenado"). El valor de este enfoque reside en encontrar múltiples soluciones a problemas ambiguos. Los resultados del estudio confirmaron que la interacción vergente de tecnologías e innovaciones, la fusión de fondos y recursos que contribuyen a la modernización del espacio de innovación, su análisis y sincronismo, excluyeron la posición de reposo en el sistema social y, por el contrario, dio lugar a una situación de dinamismo acelerado pero controlado.

The purpose of the study is to conceptualize the phenomenon of vergence of technologies and innovations in the context of building a society as a complex system by modernizing the innovation environment. To achieve the goal, general scientific and special-scientific methods of cognition were used, in particular, dialectical, formal-logical, analysis and synthesis, system-structural. The key methodological principles, spatial-topological and ontological, were presented. It is confirmed that the concept of "vergence" is the state of systems at the point of intersection of divergent and convergent processes, as well as their balancing. Vergence as a method of creative thinking was used in this study primarily to solve problems and tasks related to the synchronism of various contradictory processes (reconciles the processes of "scattering", "acceleration" and "gathering", "braking"). The value of this approach was in finding multiple solutions to ambiguous problems. The results of the study confirmed that the vergent interaction of technologies and innovations, the merging of funds and resources that contribute to the modernization of the innovation space, their analysis and synchronism, excluded the position of rest in the social system and, on the contrary, gave rise to a situation of accelerated but controlled dynamism., El propósito del estudio es conceptualizar el fenómeno de convergencia de tecnologías e innovaciones en el contexto de la construcción de una sociedad como un sistema complejo mediante la modernización del entorno de innovación. Para lograr el objetivo, se utilizaron métodos de cognición científicos generales y científicos especiales, en particular: dialéctico, lógico-formal, análisis y síntesis, sistema-estructural. Se confirma que el concepto de "vergencia" es el estado de los sistemas en el punto de intersección de procesos divergentes y convergentes, así como su equilibrio. La vergencia como método de pensamiento creativo se utilizó en este estudio principalmente para resolver problemas y tareas relacionadas con el sincronismo de varios procesos contradictorios (reconcilia los procesos de "dispersión", "aceleración" y "reunión", "frenado"). El valor de este enfoque reside en encontrar múltiples soluciones a problemas ambiguos. Los resultados del estudio confirmaron que la interacción vergente de tecnologías e innovaciones, la fusión de fondos y recursos que contribuyen a la modernización del espacio de innovación, su análisis y sincronismo, excluyeron la posición de reposo en el sistema social y, por el contrario, dio lugar a una situación de dinamismo acelerado pero controlado.

Consequently, the issue of foreign aid and its role in the international system is more important than ever before. Debates concerning the place of foreign assistance in international politics continue and draw even more scholars as well as international community members, politicians, and even journalists.

Eliciting Latent Knowledge (ELK) aims to find patterns in a capable neural network's activations that robustly track the true state of the world, especially in hard-to-verify cases where the model's output is untrusted. To further ELK research, we introduce 12 datasets and a corresponding suite of "quirky" language models (LMs) that are finetuned to make systematic errors when answering questions if and only if the keyword "Bob" is present in the prompt. We find that, especially in middle layers, linear probes usually report an LM's knowledge independently of what the LM outputs, enabling us to elicit the correct answer despite the model's untruthful output. The best probing method (logistic regression on contrast pairs) recovers 89% of the gap in AUROC between truthful and untruthful contexts, and 75% for questions harder than those used to train the probe. We also find that a mechanistic anomaly detection approach can flag untruthful behavior with 0.95 AUROC. Our results show promise for eliciting reliable knowledge from capable but untrusted models, and facilitates future research empirically investigating ELK methods., Comment: Preprint

In human-robot interaction policy design, a rule-based method is efficient, explainable, expressive and intuitive. In this paper, we present the Signal-Rule-Slot framework, which refines prior work on rule-based symbol system design and introduces a new, Bayesian notion of interaction rule utility called Causal Pathway Self-information. We offer a rigorous theoretical foundation as well as a rich open-source reference implementation Ravestate, with which we conduct user studies in text-, speech-, and vision-based scenarios. The experiments show robust contextual behaviour of our probabilistically informed rule-based system, paving the way for more effective human-machine interaction.

Schizophrenia is one of the most wide-spread mental brain disorders with complex and largely unknown etiology. To characterize the impact of schizophrenia at a cellular level, we performed single nucleus RNA sequencing of gt;190,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls (7 vs 11, respectively). In addition, to correlate data with cortical anatomy, gt;100,000 neurons were analyzed topographically by immunohistochemistry in an extended cohort of cases with schizophrenia and controls (10 vs 10). Compositional analysis of RNA sequencing data revealed reduction in relative abundance across all families of GABAergic neurons and a concomitant increase in principal neurons, which was most pronounced for supragranular subtypes (layers 2-3). Moreover, supragranular subtypes of GABAergic interneurons showed most dramatic transcriptomic changes. These results were substantiated by histological analysis, which revealed a reduction in the density of calretinin, calbindin and parvalbumin GABAergic interneurons particularly in layer 2. Common effect of schizophrenia on supragranular neuronal networks was underlined by downregulation of protein processing genes and upregulation of neuronal development/plasticity genes across supragranular subtypes of principal neurons and GABAergic interneurons. In situ hybridization and spatial transcriptomics further confirmed supragranular layer neuron vulnerability, revealing complexity of schizophrenia-affected cortical circuits. These point towards general network impairment within supragranular layers being a core substrate associated with schizophrenia symptomatology.Competing Interest StatementThe authors have declared no competing interest.

Schizophrenia is one of the most wide-spread mental brain disorders with complex and largely unknown etiology. To characterize the impact of schizophrenia at a cellular level, we performed single nucleus RNA sequencing of gt;190,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls (7 vs 11, respectively). In addition, to correlate data with cortical anatomy, gt;100,000 neurons were analyzed topographically by immunohistochemistry in an extended cohort of cases with schizophrenia and controls (10 vs 10). Compositional analysis of RNA sequencing data revealed reduction in relative abundance across all families of GABAergic neurons and a concomitant increase in principal neurons, which was most pronounced for supragranular subtypes (layers 2-3). Moreover, supragranular subtypes of GABAergic interneurons showed most dramatic transcriptomic changes. These results were substantiated by histological analysis, which revealed a reduction in the density of calretinin, calbindin and parvalbumin GABAergic interneurons particularly in layer 2. Common effect of schizophrenia on supragranular neuronal networks was underlined by downregulation of protein processing genes and upregulation of neuronal development/plasticity genes across supragranular subtypes of principal neurons and GABAergic interneurons. In situ hybridization and spatial transcriptomics further confirmed supragranular layer neuron vulnerability, revealing complexity of schizophrenia-affected cortical circuits. These point towards general network impairment within supragranular layers being a core substrate associated with schizophrenia symptomatology.Competing Interest StatementThe authors have declared no competing interest.

Останніми роками обговорюється значення збудників інфекційних та паразитарних хвороб у соматичній патології людини. Бластоцисти належать до найпоширеніших кишкових найпростіших, але їхню роль при кишкових паразитозах, а також при деяких соматичних захворюваннях вивчено недостатньо. Важливим є питання щодо патогенного потенціалу Blastocystis spp., оскільки паразита виявляють як у пацієнтів із симптомами, так і у безсимптомних носіїв. Сучасні дослідження виявили наявність зв’язку між бластоцистною інвазією і різними формами дисфункції шлунково‑кишкового тракту, зокрема синдромом подразненого кишечника, а також шкірними виявами, наприклад, уртикарною висипкою. Основ­ним методом, який використовують для клінічної діагностики бластоцистної інвазії, лишається мікроскопія, яка, незважаючи на інтенсивний розвиток імунологічних і молекулярно‑генетичних методів діагностики, часто є не тільки першим, але і достатнім етапом дослідження. В Україні з 2000 р. у звітних формах наводять випадки виявлення Blastocystis spp. при паразитологічних обстеженнях населення, але не реєструють захворюваність на бластоцистоз. У цілому частота виявлення Blastocystis spp. у населення України відповідає поширеності патогену в розвинених країнах — середній багаторічний показник за 2009 — 2018 рр. становив 4,4 на 100 тис. населення. Результати власних досліджень свідчать про більшу частоту виявлення Blastocystis spp. серед дорослого населення України переважно у пацієнтів із захворюваннями шлунково‑кишкового тракту. При обстеженні здорових дорослих осіб бластоцист виявлено у 5,2 %, при обстеженні хворих з хронічними захворюваннями шлунково‑кишкового тракту — 20,5 %, зокрема серед хворих із синдромом подразненого кишечника — 28,6 %. Всі хворі на СПК, в яких були виявлені Blastocystis spр., мали дисбіотичні порушення І або ІІ ступеня., В последние годы обсуждается значение возбудителей инфекционных и паразитарных болезней в соматической патологии человека. Бластоцисты относятся к наиболее распространенным кишечным простейшим, но их роль при кишечных паразитозах, а также при некоторых соматических заболеваниях изучена недостаточно. Важным является вопрос о патогенном потенциале Blastocystis spp., поскольку паразита выявляют как у пациентов с симптомами, так и у бессимптомных носителей. Современные исследования выявили наличие связи между бластоцистной инвазией и различными формами дисфункции желудочно‑кишечного тракта, в частности синдромом раздраженного кишечника, а также кожными проявлениями, например, уртикарной сыпью. Основным методом, который используется для клинической диагностики бластоцистной инвазии, остается микроскопия, которая, несмотря на интенсивное развитие иммунологических и молекулярно‑генетических методов диагностики, часто является не только первым, но и достаточным этапом исследования. В Украине с 2000 г. в отчетных формах приведены случаи выявления Blastocystis spp. при паразитологических обследованиях населения, но не регистрируется заболеваемость бластоцистозом. В целом частота обнаружения Blastocystis spp. у населения Украины соответствует распространенности патогена в развитых странах — средний многолетний показатель за 2009 — 2018 гг. составлял 4,4 на 100 тыс. населения. Результаты собственных исследований свидетельствуют о большей частоте выявления Blastocystis spp. среди взрослого населения Украины, преимущественно у пациентов с заболеваниями желудочно‑кишечного тракта. При обследовании здоровых взрослых лиц бластоцисты обнаружены у 5,2 %, при обследовании больных с хроническими заболеваниями желудочно‑кишечного тракта — 20,5 %, в том числе среди больных с синдромом раздраженного кишечника — 28,6 %. Все больные СПК, в которых были обнаружены Blastocystis ѕрр., имели дисбиотические нарушения І или ІІ степени., In recent years, the role of pathogens of infectious and parasitic diseases in human somatic pathology has been increasingly discussed. Blastocysts belong to the most common intestinal protozoa, but their role in intestinal parasitosis, as well as in some somatic diseases, is still poorly understood. An important question remains about the pathogenic potential of Blastocystis spp. because the parasite is detected in patients with symptoms and in asymptomatic carriers. At the same time, recent researches have shown a link between blastocyst invasion and various forms of gastrointestinal (GI) dysfunction, primarily irritable bowel syndrome (IBS), as well as skin manifestations, such as urticaria. The main method used for the clinical diagnosis of blastocyst invasion remains microscopy, which, despite the intensive development of immunological and molecular genetic methods of diagnosis, is often not only the first, but also a sufficient stage of research. Stating from the year 2000, in Ukraine the reporting forms list the cases of Blastocystis spp. detection during parasitological surveys of the population, but the blastocystosis morbidity has not being registered. In general, the frequency of detection of Blastocystis spp. in the population of Ukraine corresponds to the prevalence of the pathogen in developed countries — the average long‑term indicator for 2009 — 2018 was 4.4 per 100 thousand population. The results of our own research indicate a higher frequency of detection of Blastocystis spp. among the adult population of Ukraine, mainly in patients with gastrointestinal diseases. During the examination of healthy adults, Blastocystis spp. was detected in 5.2 ± 0.8 %, in patients with chronic gastrointestinal tract lesions — 20.5 ± 6.5 %, including the cases among patients diagnosed with IBS — 28.6 ± 9.9 %. All IBS patients with detected Blastocystis spp. demonstrated dysbiotic disorders of the 1 or 2 degrees.

The original version of this Article contained an error in the spelling of the author Andrea Asenjo-Martinez, which was incorrectly given as Andrea Asenjo Martinez. This has now been corrected in both the PDF and HTML versions of the Article.

Spatial transcriptomics is an emerging stack of technologies, which adds spatial dimension to conventional single-cell RNA-sequencing. New protocols, based on in situ sequencing or multiplexed RNA fluorescent in situ hybridization register positions of single molecules in fixed tissue slices. Analysis of such data at the level of individual cells, however, requires accurate identification of cell boundaries. While many existing methods are able to approximate cell center positions using nuclei stains, current protocols do not report robust signal on the cell membranes, making accurate cell segmentation a key barrier for downstream analysis and interpretation of the data. To address this challenge, we developed a tool for Bayesian Segmentation of Spatial Transcriptomics Data (Baysor), which optimizes segmentation considering the likelihood of transcriptional composition, size and shape of the cell. The Bayesian approach can take into account nuclear or cytoplasm staining, however can also perform segmentation based on the detected transcripts alone. We show that Baysor segmentation can in some cases nearly double the number of the identified cells, while reducing contamination. Importantly, we demonstrate that Baysor performs well on data acquired using five different spatially-resolved protocols, making it a useful general tool for analysis of high-resolution spatial data.Competing Interest StatementP.V.K serves on the Scientific Advisory Board to Celsius Therapeutics, Inc. Other authors declare no conflict of interest.

Spatial transcriptomics is an emerging stack of technologies, which adds spatial dimension to conventional single-cell RNA-sequencing. New protocols, based on in situ sequencing or multiplexed RNA fluorescent in situ hybridization register positions of single molecules in fixed tissue slices. Analysis of such data at the level of individual cells, however, requires accurate identification of cell boundaries. While many existing methods are able to approximate cell center positions using nuclei stains, current protocols do not report robust signal on the cell membranes, making accurate cell segmentation a key barrier for downstream analysis and interpretation of the data. To address this challenge, we developed a tool for Bayesian Segmentation of Spatial Transcriptomics Data (Baysor), which optimizes segmentation considering the likelihood of transcriptional composition, size and shape of the cell. The Bayesian approach can take into account nuclear or cytoplasm staining, however can also perform segmentation based on the detected transcripts alone. We show that Baysor segmentation can in some cases nearly double the number of the identified cells, while reducing contamination. Importantly, we demonstrate that Baysor performs well on data acquired using five different spatially-resolved protocols, making it a useful general tool for analysis of high-resolution spatial data.Competing Interest StatementP.V.K serves on the Scientific Advisory Board to Celsius Therapeutics, Inc. Other authors declare no conflict of interest.

Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.

Epilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.

The purpose of the present work is a detailed investigation of the dynamical evolutionof Collinder 135 and UBC 7 star clusters. We present a set of dynamical numerical simulationsusing realistic star clusterN-body modeling technique with the forward integration of thestar-by-star cluster models to the present day, based on best-available 3D coordinates and velocitiesobtained from the latest Gaia EDR3 data release. We have established that Collinder 135 and UBC 7 are probably a binary star cluster and have common origin. We carried out a full star-by-star N-body simulation of the stellar population of both clusters using the new algorithm of Single Stellar Evolution and performed a comparison of the results obtained in the observational data (like cumulative number counts), which showed a fairly good agreement., Comment: 6 pages, 6 figures, 3 tables. Proceedings IAU Symposium, 2021

The use of information and communication technologies in education, including cloud technologies, has recently become an urgent issue. The main reasons for the growing interest in cloud technologies are the need to find alternative forms of learning to traditional ones, as well as the conformity of functional capabilities of cloud technologies to modern needs of optimisation of educational branch. Application of cloud technologies in educational process requires teachers to have appropriate qualification. The aim of this work was to develop a qualification improvement model for foreign language teachers, which could help them acquire the necessary theoretical knowledge, as well as practical skills and abilities to use cloud technologies in professional activities. This paper used methods of analysis of existing models of teacher training, as well as the survey and mathematical methods of processing the results of experimental research. The model of advanced training is created in the work, which helps teachers of Philology to acquire the necessary skills and abilities of productive use of cloud technologies. In addition, it allows you to gain new knowledge in the field of foreign philology, pedagogy and psychology. According to this study, as a result of using such a model, foreign language teachers acquire the necessary skills and abilities to use cloud technologies in the educational process. They allow them to achieve didactic goals in professional activities. As this study showed, foreign language teachers can achieve didactic goals in professional activities using cloud technology through the proposed model. It was found that the developed model is highly efficient. The results of this study can be useful to scientists and educators who are engaged in finding and researching effective learning models that rely on modern technology. Prospects for future research may be to improve existing teacher training models and develop new ones in accordance with the state, O uso de tecnologias de informação e comunicação na educação, incluindo tecnologias em nuvem, tornou-se recentemente uma questão urgente. As principais razões para o crescente interesse pelas tecnologias da nuvem são a necessidade de encontrar formas alternativas de aprendizagem às tradicionais, bem como a conformidade das capacidades funcionais das tecnologias da nuvem às necessidades modernas de otimização do ramo educacional. A aplicação de tecnologias de nuvem no processo educacional exige que os professores tenham qualificação adequada. O objetivo deste trabalho foi desenvolver um modelo de melhoria de qualificação para professores de línguas estrangeiras, que pudesse ajudá-los a adquirir os conhecimentos teóricos necessários, bem como as competências práticas e habilidades para usar as tecnologias da nuvem na atividade profissional. Este artigo utilizou métodos de análise de modelos existentes de formação de professores, bem como o levantamento e métodos matemáticos de processamento de resultados de pesquisas experimentais. O modelo de formação avançada é criado no trabalho, que auxilia os professores de Filologia a adquirir as competências e habilidades necessárias ao uso produtivo das tecnologias da nuvem. Conforme este estudo mostrou, os professores de línguas estrangeiras podem atingir objetivos didáticos nas atividades profissionais utilizando a tecnologia em nuvem por meio do modelo proposto. Verificou-se que o modelo desenvolvido é altamente eficiente. Os resultados deste estudo podem ser úteis para cientistas e educadores que estão empenhados em encontrar e pesquisar modelos de aprendizagem eficazes que dependem de tecnologia moderna. As perspectivas para pesquisas futuras podem ser melhorar os modelos existentes de formação de professores e desenvolver novos de acordo com o estado das tecnologias digitais, El uso de tecnologías de la información y la comunicación en la educación, incluidas las tecnologías en la nube, se ha convertido recientemente en un problema urgente. Las principales razones del creciente interés por las tecnologías en la nube son la necesidad de encontrar formas de aprendizaje alternativas a las tradicionales, así como la conformidad de las capacidades funcionales de las tecnologías en la nube a las necesidades modernas de optimización de la rama educativa. La aplicación de tecnologías en la nube en el proceso educativo requiere que los maestros tengan la calificación adecuada. El objetivo de este trabajo fue desarrollar un modelo de mejora de la cualificación de los profesores de lenguas extranjeras, que pudiera ayudarles a adquirir los conocimientos teóricos necesarios, así como las habilidades y habilidades prácticas para utilizar las tecnologías en la nube en actividades profesionales. En este artículo se utilizaron métodos de análisis de modelos existentes de formación docente, así como métodos de encuesta y matemáticos para procesar los resultados de la investigación experimental. En el trabajo se crea el modelo de formación avanzada, que ayuda a los profesores de Filología a adquirir las competencias y habilidades necesarias de uso productivo de las tecnologías en la nube. Como mostró este estudio, los profesores de lenguas extranjeras pueden lograr objetivos didácticos en actividades profesionales utilizando tecnología en la nube a través del modelo propuesto. Se encontró que el modelo desarrollado es altamente eficiente. Los resultados de este estudio pueden ser útiles para los científicos y educadores que se dedican a encontrar e investigar modelos de aprendizaje eficaces que se basan en la tecnología moderna. Las perspectivas para la investigación futura pueden ser mejorar los modelos de formación docente existentes y desarrollar otros nuevos de acuerdo con el estado de las tecnologías digitales.

The rapid development of international cooperation and interethnic contacts entails the need to improve training in the field of tourism, including training of escort interpreters. It is known that escort interpreters must not only have skills and abilities, but also constantly improve their knowledge of foreign languages. Thus, the problem of optimizing the development of translation competence in escort interpreters is gaining importance. The aim of the study is to substantiate the need to optimize the development of translation competence in escort interpreters to work in international tourism. The article involved the following methods: theoretical review and analysis of domestic and foreign literature on the problem of research, pedagogical observation and generalization of the experience of training escort interpreters in universities. It was found that optimization of translation competence in escort interpreters will be more effective in implementing the author’s model and methodology presented in the professional. The theoretical significance of this article is that the theory and methodology of vocational education identified and established the content of translation competence and a model for optimizing its development. The practical significance lies in the focus on optimizing the translation competence in translation guides. Relevant methods and programmes have been identified, which provide for development and application in practice of professionally oriented language situations in improvement of foreign language skills. The results indicate the effectiveness of established models and methods of optimizing development of translation competence in escort interpreters to work in international tourism based on the improvement of foreign language skills.

Background and Aims Proctitis is the least extensive type of ulcerative colitis, for which rectal therapy is rarely studied and is underused. This study evaluated the efficacy, safety, and patient's preference of a novel formulation of budesonide suppository 4 mg, compared with a commercially available budesonide rectal foam 2 mg, for the treatment of mild to moderate ulcerative proctitis. Methods This was a randomised, double-blind, double-dummy, active-controlled trial. Patients were randomly assigned in a 1:1 ratio to receive either budesonide 4 mg suppository or budesonide 2 mg foam once daily for 8 weeks. The co-primary endpoints were changes from baseline to Week 8 in clinical symptoms, for which clinical remission was defined as having a modified Ulcerative Colitis-Disease Activity Index [UC-DAI] subscore for stool frequency of 0 or 1 and a subscore for rectal bleeding of 0, and mucosal healing, defined as having a modified UC-DAI subscore for mucosal appearance of 0 or 1. Using a more stringent criterion, we additionally analysed deepened mucosal healing, which was defined as a mucosal appearance subscore of 0. Patient's preference, physician's global assessment, and quality of life were also assessed and analysed. Results Overall, 286 and 291 patients were included in the 4 mg suppository and 2 mg foam groups, respectively. Budesonide 4 mg suppository met the prespecified criterion for non-inferiority to the 2 mg foam in both co-primary endpoints of clinical remission and mucosal healing. Secondary endpoints consistently supported the non-inferiority of the suppository. Trends in favour of the suppository were observed in the subgroup of mesalazine non-responders. More patients reported a preference for the suppository over rectal foam. Conclusions In patients with ulcerative proctitis, budesonide 4 mg suppository was non-inferior to budesonide 2 mg foam in efficacy, and both were safe and well tolerated.

Roboy 3.0 is an open-source tendon-driven humanoid robot that mimics the musculoskeletal system of the human body. Roboy 3.0 is being developed as a remote robotic body - or a robotic avatar - for humans to achieve remote physical presence. Artificial muscles and tendons allow it to closely resemble human morphology with 3-DoF neck, shoulders and wrists. Roboy 3.0 3-DoF joints are implemented as ball-and-socket joints. While industry provides a clear solution for 1-DoF joint pose sensing, it is not the case for the ball-and-socket joint type. In this paper we present a custom solution to estimate the pose of a ball-and-socket joint. We embed an array of magnets into the ball and an array of 3D magnetic sensors into the socket. We then, based on the changes in the magnetic field as the joint rotates, are able to estimate the orientation of the joint. We evaluate the performance of two neural network approaches using the LSTM and Bayesian-filter like DVBF. Results show that in order to achieve the same mean square error (MSE) DVBFs require significantly more time training and hyperparameter tuning compared to LSTMs, while DVBF cope with sensor noise better. Both methods are capable of real-time joint pose estimation at 37 Hz with MSE of around 0.03 rad for all three degrees of freedom combined. The LSTM model is deployed and used for joint pose estimation of Roboy 3.0's shoulder and neck joints. The software implementation and PCB designs are open-sourced under https://github.com/Roboy/ball_and_socket_estimator, Comment: Accepted at the International Symposium on Robotics Research (ISRR) 2022

AbstractThe primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

This paper evaluates the status quo of modern society and identifies the neglect of humanism as the root cause of many of today’s global challenges. Note that “smart cities” are not excluded from this indictment. The “Ptolemaic Universe” offers a means to restore our symbiosis with the environment. The ReSeT model is proposed as a tool to analyze the Ptolemaic Universe. Using ReSeT: Homo Sapiens becomes dependent on AI resulting in Homo Digitalis, with further evolution in concert with AI resulting in Homo Digitus. All of these stages are then analyzed in the context of global trusted dependability (GTD). The wellness domain, provides the design specification framework for Homo Digitus’ human-centered and resilient “smart city” ecosystem. This ultimately leads to a better world of increased wellness for Homo Hominus, with better smart cities emphasizing education and science, promoting wisdom and common sense, and rejecting violence. In summary, humanity has generated diverse social structures with erratic outcomes. On the other hand, technology provides a successful foundation for modern society especially in the Pandemic Era. However, technology’s contributions are generally not publicly acknowledged. The paper concludes with several initiatives designed to establish a trusted and resilient society.