53 research outputs found

    Scale-free memory model for multiagent reinforcement learning. Mean field approximation and rock-paper-scissors dynamics

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    A continuous time model for multiagent systems governed by reinforcement learning with scale-free memory is developed. The agents are assumed to act independently of one another in optimizing their choice of possible actions via trial-and-error search. To gain awareness about the action value the agents accumulate in their memory the rewards obtained from taking a specific action at each moment of time. The contribution of the rewards in the past to the agent current perception of action value is described by an integral operator with a power-law kernel. Finally a fractional differential equation governing the system dynamics is obtained. The agents are considered to interact with one another implicitly via the reward of one agent depending on the choice of the other agents. The pairwise interaction model is adopted to describe this effect. As a specific example of systems with non-transitive interactions, a two agent and three agent systems of the rock-paper-scissors type are analyzed in detail, including the stability analysis and numerical simulation. Scale-free memory is demonstrated to cause complex dynamics of the systems at hand. In particular, it is shown that there can be simultaneously two modes of the system instability undergoing subcritical and supercritical bifurcation, with the latter one exhibiting anomalous oscillations with the amplitude and period growing with time. Besides, the instability onset via this supercritical mode may be regarded as "altruism self-organization". For the three agent system the instability dynamics is found to be rather irregular and can be composed of alternate fragments of oscillations different in their properties.Comment: 17 pages, 7 figur

    Analyses of biomarker traits in diverse UK biobank participants identify associations missed by European-centric analysis strategies

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    Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, as well as variants rare in European populations, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in African (n = 9354), East Asian (n = 2559), and South Asian (n = 9823) ancestry UK Biobank (UKBB) participants. We adjusted for all known GWAS catalog variants for each trait, as well as novel signals identified in a recent European ancestry-focused analysis of UKBB participants. We identify 7 novel signals in African ancestry and 2 novel signals in South Asian ancestry participants (p < 1.61E−10). Many of these signals are highly plausible, including a cis pQTL for the gene encoding gamma-glutamyl transferase and PIEZO1 and G6PD variants with impacts on HbA1c through likely erythrocytic mechanisms. This work illustrates the importance of using the genetic data we already have in diverse populations, with novel discoveries possible in even modest sample sizes

    The genetic architecture of the human cerebral cortex

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    INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

    Physiologic correlates to running performance in pre-pubertal distance runners

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    In adults, four major variables have been shown to be associated with success in distance running performance: submaximal oxygen consumption (running economy), peak oxygen consumption (Peak VO2), ventilatory threshold (VT) and fractional utilisation (FU). The primary aim of this study was to describe the relationship between the 3000 m race times of run-trained prepubertal boys to these four variables. Thirteen male run-trained pre-pubertal boys (age 11.7 +/- 1.1 yrs, mean +/- SD), volunteered to take part in a 3000 m time trial and laboratory assessment, consisting of treadmill running at four submaximal speeds (8, 9.6, 11.2 and 12.8 km.h-1) as well as a peak VO2 test. The group demonstrated a heterogeneous array of peak VO2 data. A high level of association (p &#60; 0.05) was found between mass-relative peak VO2 and 3000 m time trial results (r = -0.83). In addition ventilatory threshold expressed as %peak VO2, VO2 at VT and estimated velocity at VT was also highly related to 3000 m time trial (r = -0.78, -0.77 and -0.77) respectively. Fractional utilisation (%peak VO2) was significantly (p &#60; 0.05) associated with race time at the final two submaximal running speeds only (11.2 and 12.8 km.h-1) (r = 0.61 and 0.67, respectively). Respiratory Exchange Ratio (RER) was also found to be significantly (p &#60; 0.05) associated with 3000 m race time at 11.2 and 12.8 km.h-1. Overall peak VO2 appeared to be the single most important factor associated with success at 3000 m

    Submaximal running economy in run-trained pre-pubertal boys

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    There is an increasing tendency for young children to participate in training and competitive running. The impact long-term training has upon stimulating functional physiological adaptation has yet to be fully understood. In this study cardio-respiratory and kinematic differences were assessed at submaximal and maximal exercise intensities in run-trained and non-run-trained boys. Thirty three pre-pubertal boys volunteered to take part in the study. The subjects were in two groups: 15 run-trained subjects [age 11.7 +/- 1.06 yrs, mean +/- SD] and 18 non-run-trained (control) subjects [age 11.3 +/- 0.90 yrs]. Two separate (4 x 3 min) submaximal protocols were used for the trained and non-run-trained groups, with two of the speeds overlapping for comparison purposes. In addition, all boys also performed a maximal oxygen consumption test. Mean VO2max value for the run trained group was 60.5 +/- 3.3 ml/kg/min and for the control group 51.1 +/- 4.3 ml/kg/min, (p &#60; 0.001). No significant differences were found for submaximal running economy at either comparison speed. In addition, no significant (p &#62; 0.05) differences were noted between the groups for any of the kinematic variables at the two comparison speeds. However, selected physiological differences did exist at the submaximal running speeds. The source of the differences that did exist between the two groups may be the result of training, genetic pre-selection or developmental differences between the groups

    Clinical manifestations of the ‘athlete's heart’ in prepubertal male runners

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    Cardiac findings in adult endurance athletes are well characterized, but data regarding the "athlete's heart" in children are limited. This study evaluated cardiovascular features of 10 male prepubertal distance runners ages 11-13 years compared to 18 physically active but untrained boys. Mean VO2max values on treadmill testing for the two groups were 61.2 (3.2) and 51.1 (4.3) ml.kg-1.min-1, respectively. No significant differences in the frequency of carotid bruits, cervical venous hums, heart murmurs, or third and fourth heart sounds were observed between the groups. Mean resting heart rate was 71 (9) bpm for the runners and 73 (8) for the controls (p &#62; 0.05). No significant differences were seen in EKG intervals, axes, or precordial voltages between runners and controls, and echocardiographic chamber sizes, wall thicknesses, and mass indexed to body surface area were also similar (p &#62; 0.05). This study failed to identify clinical features of the "athlete's heart" in competitive child endurance runners compared to non-trained subjects
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