224 research outputs found

    Empowerment for Continuous Agent-Environment Systems

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    This paper develops generalizations of empowerment to continuous states. Empowerment is a recently introduced information-theoretic quantity motivated by hypotheses about the efficiency of the sensorimotor loop in biological organisms, but also from considerations stemming from curiosity-driven learning. Empowemerment measures, for agent-environment systems with stochastic transitions, how much influence an agent has on its environment, but only that influence that can be sensed by the agent sensors. It is an information-theoretic generalization of joint controllability (influence on environment) and observability (measurement by sensors) of the environment by the agent, both controllability and observability being usually defined in control theory as the dimensionality of the control/observation spaces. Earlier work has shown that empowerment has various interesting and relevant properties, e.g., it allows us to identify salient states using only the dynamics, and it can act as intrinsic reward without requiring an external reward. However, in this previous work empowerment was limited to the case of small-scale and discrete domains and furthermore state transition probabilities were assumed to be known. The goal of this paper is to extend empowerment to the significantly more important and relevant case of continuous vector-valued state spaces and initially unknown state transition probabilities. The continuous state space is addressed by Monte-Carlo approximation; the unknown transitions are addressed by model learning and prediction for which we apply Gaussian processes regression with iterated forecasting. In a number of well-known continuous control tasks we examine the dynamics induced by empowerment and include an application to exploration and online model learning

    Stanniocalcin 1 effects on the renal gluconeogenesis pathway in rat and fish

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    The mammalian kidney contributes significantly to glucose homeostasis through gluconeogenesis. Considering that stanniocalcin 1 (STC1) regulates ATP production, is synthesized and acts in different cell types of the nephron, the present study hypothesized that STC1 may be implicated in the regulation of gluconeogenesis in the vertebrate kidney. Human STC1 strongly reduced gluconeogenesis from C-14-glutamine in rat renal medulla (MD) slices but not in renal cortex (CX), nor from C-14-lactic acid. Total PEPCK activity was markedly reduced by hSTC1 in MD but not in CX. Pck2 (mitochondrial PEPCK isoform) was down-regulated by hSTC1 in MD but not in CX. In fish (Dicentrarchus labrax) kidney slices, both STC1-A and -B isoforms decreased gluconeogenesis from C-14-acid lactic, while STC1-A increased gluconeogenesis from C-14-glutamine. Overall, our results demonstrate a role for STC1 in the control of glucose synthesis via renal gluconeogenesis in mammals and suggest that it may have a similar role in teleost fishes. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Brazil; Foundation for Science and Technology of Portugal [PTDC/MAR/121279/2010]; bilateral programme CAPES (Brazil)/GRICES (Portugal) CAPES/GRICES [215/08]info:eu-repo/semantics/publishedVersio

    Metal enrichment processes

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    There are many processes that can transport gas from the galaxies to their environment and enrich the environment in this way with metals. These metal enrichment processes have a large influence on the evolution of both the galaxies and their environment. Various processes can contribute to the gas transfer: ram-pressure stripping, galactic winds, AGN outflows, galaxy-galaxy interactions and others. We review their observational evidence, corresponding simulations, their efficiencies, and their time scales as far as they are known to date. It seems that all processes can contribute to the enrichment. There is not a single process that always dominates the enrichment, because the efficiencies of the processes vary strongly with galaxy and environmental properties.Comment: 18 pages, 8 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 17; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

    Modeling of the condyle elements within a biomechanical knee model

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    The development of a computational multibody knee model able to capture some of the fundamental properties of the human knee articulation is presented. This desideratum is reached by including the kinetics of the real knee articulation. The research question is whether an accurate modeling of the condyle contact in the knee will lead to reproduction of the complex combination of flexion/extension, abduction/adduction and tibial rotation ob-served in the real knee? The model is composed by two anatomic segments, the tibia and the femur, whose characteristics are functions of the geometric and anatomic properties of the real bones. The biomechanical model characterization is developed under the framework of multibody systems methodologies using Cartesian coordinates. The type of approach used in the proposed knee model is the joint surface contact conditions between ellipsoids, represent-ing the two femoral condyles, and points, representing the tibial plateau and the menisci. These elements are closely fitted to the actual knee geometry. This task is undertaken by con-sidering a parameter optimization process to replicate experimental data published in the lit-erature, namely that by Lafortune and his co-workers in 1992. Then, kinematic data in the form of flexion/extension patterns are imposed on the model corresponding to the stance phase of the human gait. From the results obtained, by performing several computational simulations, it can be observed that the knee model approximates the average secondary mo-tion patterns observed in the literature. Because the literature reports considerable inter-individual differences in the secondary motion patterns, the knee model presented here is also used to check whether it is possible to reproduce the observed differences with reasonable variations of bone shape parameters. This task is accomplished by a parameter study, in which the main variables that define the geometry of condyles are taken into account. It was observed that the data reveal a difference in secondary kinematics of the knee in flexion ver-sus extension. The likely explanation for this fact is the elastic component of the secondary motions created by the combination of joint forces and soft tissue deformations. The proposed knee model is, therefore, used to investigate whether this observed behavior can be explained by reasonable elastic deformations of the points representing the menisci in the model.Fundação para a Ciência e a Tecnologia (FCT) - PROPAFE – Design and Development of a Patello-Femoral Prosthesis (PTDC/EME-PME/67687/2006), DACHOR - Multibody Dynamics and Control of Hybrid Active Orthoses MIT-Pt/BSHHMS/0042/2008, BIOJOINTS - Development of advanced biological joint models for human locomotion biomechanics (PTDC/EME-PME/099764/2008)

    Palaeoenvironmental control on distribution of crinoids in the Bathonian (Middle Jurassic) of England and France

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    Bulk sampling of a number of different marine and marginal marine lithofacies in the British Bathonian has allowed us to assess the palaeoenvironmental distribution of crinoids for the first time. Although remains are largely fragmentary, many species have been identified by comparison with articulated specimens from elsewhere, whilst the large and unbiased sample sizes allowed assessment of relative proportions of different taxa. Results indicate that distribution of crinoids well corresponds to particular facies. Ossicles of Chariocrinus and Balanocrinus dominate in deeper-water and lower-energy facies,with the former extending further into shallower-water facies than the latter. Isocrinus dominates in shallower water carbonate facies, accompanied by rarer comatulids, and was also present in the more marine parts of lagoons. Pentacrinites remains are abundant in very high-energy oolite shoal lithofacies. The presence of millericrinids within one, partly allochthonous lithofacies suggests the presence of an otherwise unknown hard substrate from which they have been transported. These results are compared to crinoid assemblages from other Mesozoic localities, and it is evident that the same morphological ad-aptations are present within crinoids from similar lithofacies throughout the Jurassic and Early Cretaceous

    Animal models for COVID-19

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    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (first detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the findings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19

    Nanoparticles for Applications in Cellular Imaging

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    In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, and gold nanoparticles) and their impact on the ability to image biological components in fixed cells. The review also discusses factors influencing nanoparticle imaging and uptake in live cells in vitro. Due to their unique size-dependent properties nanoparticles offer numerous advantages over traditional dyes and proteins. For example, the photostability, narrow emission peak, and ability to rationally modify both the size and surface chemistry of Quantum Dots allow for simultaneous analyses of multiple targets within the same cell. On the other hand, the surface characteristics of nanometer sized TiO2allow efficient conjugation to nucleic acids which enables their retention in specific subcellular compartments. We discuss cellular uptake mechanisms for the internalization of nanoparticles and studies showing the influence of nanoparticle size and charge and the cell type targeted on nanoparticle uptake. The predominant nanoparticle uptake mechanisms include clathrin-dependent mechanisms, macropinocytosis, and phagocytosis

    Meta-analysis of type 2 Diabetes in African Americans Consortium

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    Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe
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