234 research outputs found

    Integrating Brain and Biomechanical Models—A New Paradigm for Understanding Neuro-muscular Control

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    To date, realistic models of how the central nervous system governs behavior have been restricted in scope to the brain, brainstem or spinal column, as if these existed as disembodied organs. Further, the model is often exercised in relation to an in vivo physiological experiment with input comprising an impulse, a periodic signal or constant activation, and output as a pattern of neural activity in one or more neural populations. Any link to behavior is inferred only indirectly via these activity patterns. We argue that to discover the principles of operation of neural systems, it is necessary to express their behavior in terms of physical movements of a realistic motor system, and to supply inputs that mimic sensory experience. To do this with confidence, we must connect our brain models to neuro-muscular models and provide relevant visual and proprioceptive feedback signals, thereby closing the loop of the simulation. This paper describes an effort to develop just such an integrated brain and biomechanical system using a number of pre-existing models. It describes a model of the saccadic oculomotor system incorporating a neuromuscular model of the eye and its six extraocular muscles. The position of the eye determines how illumination of a retinotopic input population projects information about the location of a saccade target into the system. A pre-existing saccadic burst generator model was incorporated into the system, which generated motoneuron activity patterns suitable for driving the biomechanical eye. The model was demonstrated to make accurate saccades to a target luminance under a set of environmental constraints. Challenges encountered in the development of this model showed the importance of this integrated modeling approach. Thus, we exposed shortcomings in individual model components which were only apparent when these were supplied with the more plausible inputs available in a closed loop design. Consequently we were able to suggest missing functionality which the system would require to reproduce more realistic behavior. The construction of such closed-loop animal models constitutes a new paradigm of computational neurobehavior and promises a more thoroughgoing approach to our understanding of the brain’s function as a controller for movement and behavior

    Neurophysiological consequences of synapse loss in progressive supranuclear palsy

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    Synaptic loss occurs early in many neurodegenerative diseases and contributes to cognitive impairment even in the absence of gross atrophy. Currently, for human disease there are few formal models to explain how cortical networks underlying cognition are affected by synaptic loss. We advocate that biophysical models of neurophysiology offer both a bridge from clinical to preclinical models of pathology, and quantitative assays for experimental medicine. Such biophysical models can also disclose hidden neuronal dynamics generating neurophysiological observations like electro- and magneto-encephalography. Here, we augment a biophysically informed mesoscale model of human cortical function by inclusion of synaptic density estimates as captured by [11C]UCB-J positron emission tomography, and provide insights into how regional synapse loss affects neurophysiology. We use the primary tauopathy of progressive supranuclear palsy (Richardson's syndrome) as an exemplar condition, with high clinicopathological correlations. Progressive supranuclear palsy causes a marked change in cortical neurophysiology in the presence of mild cortical atrophy and is associated with a decline in cognitive functions associated with the frontal lobe. Using parametric empirical Bayesian inversion of a conductance-based canonical microcircuit model of magnetoencephalography data, we show that the inclusion of regional synaptic density-as a subject-specific prior on laminar specific neuronal populations-markedly increases model evidence. Specifically, model comparison suggests that a reduction in synaptic density in inferior frontal cortex affects superficial and granular layer glutamatergic excitation. This predicted individual differences in behaviour, demonstrating the link between synaptic loss, neurophysiology, and cognitive deficits. The method we demonstrate is not restricted to progressive supranuclear palsy or the effects of synaptic loss: such pathology-enriched dynamic causal models can be used to assess the mechanisms of other neurological disorders, with diverse non-invasive measures of pathology, and is suitable to test the effects of experimental pharmacology

    riboviz 2:A flexible and robust ribosome profiling data analysis and visualization workflow

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    MOTIVATION: Ribosome profiling, or Ribo-seq, is the state-of-the-art method for quantifying protein synthesis in living cells. Computational analysis of Ribo-seq data remains challenging due to the complexity of the procedure, as well as variations introduced for specific organisms or specialized analyses. RESULTS: We present riboviz 2, an updated riboviz package, for the comprehensive transcript-centric analysis and visualization of Ribo-seq data. riboviz 2 includes an analysis workflow built on the Nextflow workflow management system for end-to-end processing of Ribo-seq data. riboviz 2 has been extensively tested on diverse species and library preparation strategies, including multiplexed samples. riboviz 2 is flexible and uses open, documented file formats, allowing users to integrate new analyses with the pipeline. AVAILABILITY AND IMPLEMENTATION: riboviz 2 is freely available at github.com/riboviz/riboviz

    A new rhynchocephalian from the late jurassic of Germany with a dentition that is unique amongst tetrapods.

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    Rhynchocephalians, the sister group of squamates (lizards and snakes), are only represented by the single genus Sphenodon today. This taxon is often considered to represent a very conservative lineage. However, rhynchocephalians were common during the late Triassic to latest Jurassic periods, but rapidly declined afterwards, which is generally attributed to their supposedly adaptive inferiority to squamates and/or Mesozoic mammals, which radiated at that time. New finds of Mesozoic rhynchocephalians can thus provide important new information on the evolutionary history of the group. A new fossil relative of Sphenodon from the latest Jurassic of southern Germany, Oenosaurus muehlheimensis gen. et sp. nov., presents a dentition that is unique amongst tetrapods. The dentition of this taxon consists of massive, continuously growing tooth plates, probably indicating a crushing dentition, thus representing a previously unknown trophic adaptation in rhynchocephalians. The evolution of the extraordinary dentition of Oenosaurus from the already highly specialized Zahnanlage generally present in derived rhynchocephalians demonstrates an unexpected evolutionary plasticity of these animals. Together with other lines of evidence, this seriously casts doubts on the assumption that rhynchocephalians are a conservative and adaptively inferior lineage. Furthermore, the new taxon underlines the high morphological and ecological diversity of rhynchocephalians in the latest Jurassic of Europe, just before the decline of this lineage on this continent. Thus, selection pressure by radiating squamates or Mesozoic mammals alone might not be sufficient to explain the demise of the clade in the Late Mesozoic, and climate change in the course of the fragmentation of the supercontinent of Pangaea might have played a major role

    Secret Codes: The Hidden Curriculum of Semantic Web Technologies

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    There is a long tradition in education of examination of the hidden curriculum, those elements which are implicit or tacit to the formal goals of education. This article draws upon that tradition to open up for investigation the hidden curriculum and assumptions about students and knowledge that are embedded in the coding undertaken to facilitate learning through information technologies, and emerging ‘semantic technologies’ in particular. Drawing upon an empirical study of case-based pedagogy in higher education, we examine the ways in which code becomes an actor in both enabling and constraining knowledge, reasoning, representation and students. The article argues that how this occurs, and to what effect, is largely left unexamined and becomes part of the hidden curriculum of electronically mediated learning that can be more explicitly examined by positioning technologies in general, and code in particular, as actors rather than tools. This points to a significant research agenda in technology enhanced learning

    The principle of situated practice in literacy learning: students’ perspectives

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    O artigo resulta de uma investigação realizada no âmbito de uma iniciativa governamental destinada a melhorar os níveis de literacia nas séries iniciais do ensino fundamental em Portugal. A investigadora estudou as representações dos alunos sobre essa experiência por meio da realização de entrevistas em grupo. Este artigo analisa os dados referentes às representações dos alunos sobre uma das dimensões pedagógicas centrais da aprendizagem da literacia, nomeadamente a constituída pela prática situada. A análise qualitativa revela representações muito positivas sobre a prática que situou a aprendizagem, tendo os alunos expressado opiniões e sentimentos extremamente favoráveis sobre a prática de aprendizagem de literacia que experimentaram. A análise dos dados desvelou ainda que o contexto que situou a aprendizagem foi ativo, lúdico, colaborativo e mediado pelas TIC. Esses resultados fundamentam, do ponto de vista único dos próprios aprendentes, uma redefinição do entendimento atual do princípio da prática situada da literacia nas séries iniciais do ensino fundamental, no sentido do reconhecimento da centralidade da ludicidade nessa aprendizagem.This article derives from research developed in the context of the implementation of a governmental initiative aimed to enhance literacy learning in primary education in Portugal. The researcher studied students’ representations about their learning experience through group interviews. This article focuses on data concerning students’ representations about one of the central pedagogical dimensions of literacy learning, namely situated practice. Qualitative analysis revealed students’ very positive representations about the practice which situated their learning, as they expressed extremely favourable opinions and feelings. Data analysis further unveiled that the context of learning was active, playful, collaborative, and mediated by ICT. Such results provide foundations for a theoretical redefinition of current conceptions of situated practice by evidencing the centrality of playfulness as learning practice in the education of the first grades of primary education. This is an original contribution made from the perspectives of learners themselves(undefined)info:eu-repo/semantics/publishedVersio

    The spread of marine anoxia on the northern Tethys margin during the Paleocene-Eocene Thermal Maximum

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    Records of the paleoenvironmental changes that occurred during the Paleocene-Eocene Thermal Maximum (PETM) are preserved in sedimentary rocks along the margins of the former Tethys Ocean and Peri-Tethys. This paper presents new geochemical data that constrain paleoproductivity, sediment delivery, and seawater redox conditions, from three sites that were located in the Peri-Tethys region. Trace and major element, iron speciation, and biomarker data indicate that water column anoxia was established during episodes when inputs of land-derived higher plant organic carbon and highly weathered detrital clays and silts became relatively higher. Anoxic conditions are likely to have been initially caused by two primary processes: (i) oxygen consumption by high rates of marine productivity, initially stimulated by the rapid delivery of terrestrially derived organic matter and nutrients, and (ii) phosphorus regeneration from seafloor sediments. The role of the latter process requires further investigation before its influence on the spread of deoxygenated seawater during the PETM can be properly discerned. Other oxygen-forcing processes, such as temperature/salinity-driven water column stratification and/or methane oxidation, are considered to have been relatively less important in the study region. Organic carbon enrichments occur only during the initial stages of the PETM as defined by the negative carbon isotope excursions at each site. The lack of observed terminal stage organic carbon enrichment does not support a link between PETM climate recovery and the sequestration of excess atmospheric CO2 as organic carbon in this region; such a feedback may, however, have been important in the early stages of the PETM

    Meaning between, in, and around words, gestures and postures: multimodal meaning making in children's classroom communication

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    The view of language from a social semiotic perspective is clear. Language is one of many semiotic resources we employ in our communicative practices. That is to say that while language is at times dominant, it always operates within a multimodal frame and furthermore, at times modes other than language are dominant. The proposed 2014 National Curriculum for the UK, on the other hand, values pupils' face-to-face classroom interaction in terms of standard spoken English (i.e. in terms of the mode of language alone). This paper offers examples demonstrating how embodied modes such as gesture, posture, facial expression, gaze and haptics work in conjunction with speech in children's collaborative construction of knowledge. In other words, what may have been previously conceived as gaps and silences - often interpreted as an absence of language - are in fact instantiations of the work of semiotic modes other than language. In order to consider this closely, this paper offers evidence from a multimodal micro-analysis of pupil-to-pupil, face-to-face interaction in one science lesson in a Year Five UK Primary classroom. It demonstrates how children's meaning-making is achieved through apt use of all available semiotic resources
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