182 research outputs found

    Transferable Multi-Agent Reinforcement Learning with Dynamic Participating Agents

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    We study multi-agent reinforcement learning (MARL) with centralized training and decentralized execution. During the training, new agents may join, and existing agents may unexpectedly leave the training. In such situations, a standard deep MARL model must be trained again from scratch, which is very time-consuming. To tackle this problem, we propose a special network architecture with a few-shot learning algorithm that allows the number of agents to vary during centralized training. In particular, when a new agent joins the centralized training, our few-shot learning algorithm trains its policy network and value network using a small number of samples; when an agent leaves the training, the training process of the remaining agents is not affected. Our experiments show that using the proposed network architecture and algorithm, model adaptation when new agents join can be 100+ times faster than the baseline. Our work is applicable to any setting, including cooperative, competitive, and mixed.Comment: 10 pages, 7 figure

    Genetic Variation and Antioxidant Response Gene Expression in the Bronchial Airway Epithelium of Smokers at Risk for Lung Cancer

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    Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. As a first step in applying functional genomic analysis to population studies, we have examined the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment analysis showed that the NRF2-mediated, antioxidant response element (ARE)-regulated genes, were significantly lower in SC, when compared with expression levels in SNC. Importantly, we found that the expression of MAFG (a binding partner of NRF2) was correlated with the expression of ARE genes, suggesting MAFG levels may limit target gene induction. Bioinformatically we identified single nucleotide polymorphisms (SNPs) in putative ARE genes and to test the impact of genetic variation, we genotyped these putative regulatory SNPs and other tag SNPs in selected NRF2 pathway genes. Sequencing MAFG locus, we identified 30 novel SNPs and two were associated with either gene expression or lung cancer status among smokers. This work demonstrates an analysis approach that integrates bioinformatics pathway and transcription factor binding site analysis with genotype, gene expression and disease status to identify SNPs that may be associated with individual differences in gene expression and/or cancer status in smokers. These polymorphisms might ultimately contribute to lung cancer risk via their effect on the airway gene expression response to tobacco-smoke exposure.Intramural Research Program of the National Institute of Environmental Health Sciences; National Institutes of Health (Z01 ES100475, U01ES016035, R01CA124640

    Macroscopic fundamental diagram with volume-delay relationship: model derivation, empirical validation and invariance property

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    This paper presents a macroscopic fundamental diagram model with volume-delay relationship (MFD-VD) for road traffic networks, by exploring two new data sources: license plate cameras (LPCs) and road congestion indices (RCIs). We derive a first-order, nonlinear and implicit ordinary differential equation involving the network accumulation (the volume) and average congestion index (the delay), and use empirical data from a 266 km2^2 urban network to fit an accumulation-based MFD with R2>0.9R^2>0.9. The issue of incomplete traffic volume observed by the LPCs is addressed with a theoretical derivation of the observability-invariant property: The ratio of traffic volume to the critical value (corresponding to the peak of the MFD) is independent of the (unknown) proportion of those detected vehicles. Conditions for such a property to hold is discussed in theory and verified empirically. This offers a practical way to estimate the ratio-to-critical-value, which is an important indicator of network saturation and efficiency, by simply working with a finite set of LPCs. The significance of our work is the introduction of two new data sources widely available to study empirical MFDs, as well as the removal of the assumptions of full observability, known detection rates, and spatially uniform sensors, which are typically required in conventional approaches based on loop detector and floating car data.Comment: 31 pages, 17 figure

    Divergent Evolution of Human p53 Binding Sites: Cell Cycle Versus Apoptosis

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    The p53 tumor suppressor is a sequence-specific pleiotropic transcription factor that coordinates cellular responses to DNA damage and stress, initiating cell-cycle arrest or triggering apoptosis. Although the human p53 binding site sequence (or response element [RE]) is well characterized, some genes have consensus-poor REs that are nevertheless both necessary and sufficient for transactivation by p53. Identification of new functional gene regulatory elements under these conditions is problematic, and evolutionary conservation is often employed. We evaluated the comparative genomics approach for assessing evolutionary conservation of putative binding sites by examining conservation of 83 experimentally validated human p53 REs against mouse, rat, rabbit, and dog genomes and detected pronounced conservation differences among p53 REs and p53-regulated pathways. Bona fide NRF2 (nuclear factor [erythroid-derived 2]-like 2 nuclear factor) and NFκB (nuclear factor of kappa light chain gene enhancer in B cells) binding sites, which direct oxidative stress and innate immunity responses, were used as controls, and both exhibited high interspecific conservation. Surprisingly, the average p53 RE was not significantly more conserved than background genomic sequence, and p53 REs in apoptosis genes as a group showed very little conservation. The common bioinformatics practice of filtering RE predictions by 80% rodent sequence identity would not only give a false positive rate of ∼19%, but miss up to 57% of true p53 REs. Examination of interspecific DNA base substitutions as a function of position in the p53 consensus sequence reveals an unexpected excess of diversity in apoptosis-regulating REs versus cell-cycle controlling REs (rodent comparisons: p < 1.0 e−12). While some p53 REs show relatively high levels of conservation, REs in many genes such as BAX, FAS, PCNA, CASP6, SIVA1, and P53AIP1 show little if any homology to rodent sequences. This difference suggests that among mammalian species, evolutionary conservation differs among p53 REs, with some having ancient ancestry and others of more recent origin. Overall our results reveal divergent evolutionary pressure among the binding targets of p53 and emphasize that comparative genomics methods must be used judiciously and tailored to the evolutionary history of the targeted functional regulatory regions
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