Replication Kinetics Research Articles

Unveiling New Druggable Pockets in Influenza Non-Structural Protein 1: NS1-Host Interactions as Antiviral Targets for Flu.

Influenza viruses are responsible for significant morbidity and mortality worldwide in winter seasonal outbreaks and in flu pandemics. Influenza viruses have a high rate of evolution, requiring annual vaccine updates and severely diminishing the effectiveness of the available antivirals. Identifying novel viral targets and developing new effective antivirals is an urgent need. One of the most promising new targets for influenza antiviral therapy is non-structural protein 1 (NS1), a highly conserved protein exclusively expressed in virus-infected cells that mediates essential functions in virus replication and pathogenesis. Interaction of NS1 with the host proteins PI3K and TRIM25 is paramount for NS1's role in infection and pathogenesis by promoting viral replication through the inhibition of apoptosis and suppressing interferon production, respectively. We, therefore, conducted an analysis of the druggability of this viral protein by performing molecular dynamics simulations on full-length NS1 coupled with ligand pocket detection. We identified several druggable pockets that are partially conserved throughout most of the simulation time. Moreover, we found out that some of these druggable pockets co-localize with the most stable binding regions of the protein-protein interaction (PPI) sites of NS1 with PI3K and TRIM25, which suggests that these NS1 druggable pockets are promising new targets for antiviral development.

Mouse-Adapted SARS-CoV-2 MA10 Strain Displays Differential Pulmonary Tropism and Accelerated Viral Replication, Neurodissemination, and Pulmonary Host Responses in K18-hACE2 Mice.

Several models were developed to study the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the in vivo efficacy of vaccines and therapeutics. Since wild-type mice are naturally resistant to infection by ancestral SARS-CoV-2 strains, several transgenic mouse models expressing human angiotensin-converting enzyme 2 (hACE2) were developed. An alternative approach has been to develop mouse-adapted SARS-CoV-2 strains. Here, we compared the clinical progression, viral replication kinetics and dissemination, pulmonary tropism, and host innate immune response dynamics between the mouse-adapted MA10 strain and its parental strain (USA-WA1/2020) following intranasal inoculation of K18-hACE2 mice, a widely used model. Compared to its parental counterpart, the MA10 strain induced earlier clinical decline with significantly higher viral replication and earlier neurodissemination. Importantly, the MA10 strain also showed a wider tropism, with infection of bronchiolar epithelia. While both SARS-CoV-2 strains induced comparable pulmonary cytokine/chemokine responses, many proinflammatory and monocyte-recruitment chemokines, such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IP-10/CXCL10, and MCP-1/CCL2, showed an earlier peak in MA10-infected mice. Furthermore, both strains induced a similar downregulation of murine Ace2, with only a transient downregulation of Tmprss2 and no alterations in hACE2 expression. Overall, these data demonstrate that in K18-hACE2 mice, the MA10 strain has a pulmonary tropism that more closely resembles SARS-CoV-2 tropism in humans (airways and pneumocytes) than its parental strain. Its rapid replication and neurodissemination and early host pulmonary responses can have a significant impact on the clinical outcomes of infection and are, therefore, critical features to consider for study designs using these strains and mouse model. IMPORTANCE The COVID-19 pandemic, caused by SARS-CoV-2, is still significantly impacting health care systems around the globe. Refined animal models are needed to study SARS-CoV-2 pathogenicity as well as efficacy of vaccines and therapeutics. In line with this, thorough evaluation of animal models and virus strains/variants are paramount for standardization and meaningful comparisons. Here, we demonstrated differences in replication dynamics between the Wuhan-like USA-WA1/2020 strain and the derivative mouse-adapted MA10 strain in K18-hACE2 mice. The MA10 strain showed accelerated viral replication and neurodissemination, differential pulmonary tropism, and earlier pulmonary innate immune responses. The observed differences allow us to better refine experimental designs when considering the use of the MA10 strain in the widely utilized K18-hACE2 murine model.

DNA replication: Mechanisms and therapeutic interventions for diseases.

Accurate and integral cellular DNA replication is modulated by multiple replication-associated proteins, which is fundamental to preserve genome stability. Furthermore, replication proteins cooperate with multiple DNA damage factors to deal with replication stress through mechanisms beyond their role in replication. Cancer cells with chronic replication stress exhibit aberrant DNA replication and DNA damage response, providing an exploitable therapeutic target in tumors. Numerous evidence has indicated that posttranslational modifications (PTMs) of replication proteins present distinct functions in DNA replication and respond to replication stress. In addition, abundant replication proteins are involved in tumorigenesis and development, which act as diagnostic and prognostic biomarkers in some tumors, implying these proteins act as therapeutic targets in clinical. Replication-target cancer therapy emerges as the times require. In this context, we outline the current investigation of the DNA replication mechanism, and simultaneously enumerate the aberrant expression of replication proteins as hallmark for various diseases, revealing their therapeutic potential for target therapy. Meanwhile, we also discuss current observations that the novel PTM of replication proteins in response to replication stress, which seems to be a promising strategy to eliminate diseases.

Dysbiosis of the stool DNA and RNA virome in Crohn's disease.

Pathogenesis of Crohn's disease (CD) relates to gut microbiome dysbiosis. However, less is known about the viral microbiome, consisting of bacteriophages and eukaryotic viruses, in CD. Here, we profiled the stool virome, viral functions, and viral-bacterial correlations that involved in CD pathogenesis. Metagenomics and metaviromics with novel viral identification and data analysis workflow were performed on stool of non-CD household controls, CD flare and remission patients. Both bacteriome and DNA/RNA virome alterations were characterized and correlated with disease status. There was a decreased diversity and extreme heterogeneity in both DNA and RNA virome in CD. We observed CD-specific dysbiosis in virome, particularly the prominent DNA eukaryotic Torque teno virus (TTV), disease-associated Faecalibacterium phage and Escherichia phage, and RNA tomato diet-related virus in CD, while some diverse prokaryotic viruses were more abundant in healthy subjects. Compared with the remission, inflammation-associated eukaryotic TTV and prokaryotic staphylococcus phages were predominated in the flare, and displayed a link with complications and multiple therapeutic approaches. Multiple viral functions, particularly functions of viral DNA replication, integration and modification as well as the eukaryotic TTV-related capsid protein, were markedly enriched in CD. Furthermore, the virus-bacteria interactions became more specialized in CD, and the combination of bacteriome and virome composition provided better classification between CD and health. Our study presents a global view of the comprehensive viral component change in the CD patients' gut microbiome, and highlights the great potential of virome biomarkers in pathogenesis and accurate diagnostics of CD risk and disease status. This article is protected by copyright. All rights reserved.

Evolutionary game decision-making method for network attack and defense based on regret minimization algorithm

In view of the differences and limitations of the cognitive abilities of both sides of network security attack and defense, the current network defense decision-making methods using game theory are mostly based on the assumption that the participants of attack and defense are completely rational, which is difficult to apply to the actual network attack and defense scenarios, resulting in poor practicality of defense decision-making. In order to better fit with the scenario of imperfect rational attack and defense games, we apply evolutionary game theory to describe the evolution process of attack and defense games under imperfect rationality, and extend the static analysis in the traditional game into a dynamic evolution process. Regret minimization (RM) algorithm is used to optimize the strategy learning mechanism to ensure the randomness and convergence of the strategy learning. Therefore, an evolutionary game decision model of network attack and defense based on RM algorithm is constructed. The optimal defense decision method is given by solving the evolutionary stable equilibrium, and the evolutionary trajectory of the optimal strategy of both sides is described. The results of numerical experiments verify the science and effectiveness of the model and method, and analyze and summarize the evolution rules of different attack and defense strategies under different states. Meanwhile, compared with the network defense decision method based on traditional replication dynamics, the convergence rate of the optimal defense strategy is improved by 12.8%, which proves the superiority of the proposed method in learning rate.

Darwinian evolution as Brownian motion on the simplex: A geometric perspective on stochastic replicator dynamics

We prove that stochastic replicator dynamics can be interpreted as intrinsic Brownian motion on the simplex equipped with the Aitchison geometry. As an immediate consequence, we derive three approximation results in the spirit of Wong–Zakai approximation, Donsker’s invariance principle and a JKO-scheme. Using the Fokker–Planck equation and Wasserstein-contraction estimates, we also study the long time behavior of the stochastic replicator equation, as an example of a nongradient drift diffusion on the Aitchison simplex.

Adeno-Associated Virus Monoinfection Induces a DNA Damage Response and DNA Repair That Contributes to Viral DNA Replication.

Adeno-associated virus (AAV) belongs to the Dependoparvovirus genus of the Parvoviridae family. AAV replication relies on a helper virus, such as adenovirus (Ad). Co-infection of AAV and Ad induces a DNA damage response (DDR), although its function in AAV DNA replication remains unknown. In this study, monoinfection of AAV2 in HEK293T cells expressing a minimal set of Ad helper genes was used to investigate the role of the DDR solely induced by AAV. We found that AAV2 DNA replication, but not single stranded (ss)DNA genome accumulation and Rep expression only, induced a robust DDR in HEK293T cells. The induced DDR featured the phosphorylation of replication protein A32 (RPA32), histone variant H2AX (H2A histone family member X), and all 3 phosphatidylinositol 3-kinase-related kinases (PIKKs). We also found that the kinase ataxia telangiectasia and Rad3-related protein (ATR) plays a major role in AAV2 DNA replication and that Y family DNA repair DNA polymerases η (Pol η) and Pol κ contribute to AAV2 DNA replication both in vitro and in HEK293T cells. Knockout of Pol η and Pol κ in HEK293T cells significantly decreased wild-type AAV2 replication and recombinant AAV2 production. Thus, our study has proven that AAV2 DNA replication induces a DDR, which in turn initiates a DNA repairing process that partially contributes to the viral genome amplification in HEK293T cells. IMPORTANCE Recombinant AAV (rAAV) has emerged as one of the preferred delivery vectors for clinical gene therapy. rAAV production in HEK293 cells by transfection of a rAAV transgene plasmid, an AAV Rep and Cap expression packaging plasmid, and an Ad helper plasmid remains the popular method. Here, we demonstrated that the high fidelity Y family DNA repair DNA polymerase, Pol η, and Pol κ, plays a significant role in AAV DNA replication and rAAV production in HEK293T cells. Understanding the AAV DNA replication mechanism in HEK293T cells could provide clues to increase rAAV vector yield produced from the transfection method. We also provide evidence that the ATR-mediated DNA repair process through Pol η and Pol κ is one of the mechanisms to amplify AAV genome, which could explain AAV replication and rAAV ssDNA genome conversion in mitotic quiescent cells.

Genome-wide measurement of DNA replication fork directionality and quantification of DNA replication initiation and termination with Okazaki fragment sequencing.

Studying the dynamics of genome replication in mammalian cells has been historically challenging. To reveal the location of replication initiation and termination in the human genome, we developed Okazaki fragment sequencing (OK-seq), a quantitative approach based on the isolation and strand-specific sequencing of Okazaki fragments, the lagging strand replication intermediates. OK-seq quantitates the proportion of leftward- and rightward-oriented forks at every genomic locus and reveals the location and efficiency of replication initiation and termination events. Here we provide the detailed experimental procedures for performing OK-seq in unperturbed cultured human cells and budding yeast and the bioinformatics pipelines for data processing and computation of replication fork directionality. Furthermore, we present the analytical approach based on a hidden Markov model, which allows automated detection of ascending, descending and flat replication fork directionality segments revealing the zones of replication initiation, termination and unidirectional fork movement across the entire genome. These tools are essential for the accurate interpretation of human and yeast replication programs. The experiments and the data processing can be accomplished within six days. Besides revealing the genome replication program in fine detail, OK-seq has been instrumental in numerous studies unravelling mechanisms of genome stability, epigenome maintenance and genome evolution.

Systemic-Risk and Evolutionary Stable Strategies in a Financial Network

We consider a financial network represented at any time instance by a random liability graph which evolves over time. The agents connect through credit instruments borrowed from each other or through direct lending, and these create the liability edges. These random edges are modified (locally) by the agents over time, as they learn from their experiences and (possibly imperfect) observations. The settlement of the liabilities of various agents at the end of the contract period (at any time instance) can be expressed as solutions of random fixed point equations. Our first step is to derive the solutions of these equations (asymptotically and one for each time instance), using a recent result on random fixed point equations. The agents, at any time instance, adapt one of the two available strategies, risky or less risky investments, with an aim to maximize their returns. We aim to study the emerging strategies of such replicator dynamics that drives the financial network. We theoretically reduce the analysis of the complex system to that of an appropriate ordinary differential equation (ODE). Using the attractors of the resulting ODE we show that the replicator dynamics converges to one of the two pure evolutionary stable strategies (all risky or all less risky agents); one can have mixed limit only when the observations are imperfect. We verify our theoretical findings using exhaustive Monte Carlo simulations. The dynamics avoid the emergence of the systemic-risk regime (where majority default). However, if all the agents blindly adapt risky strategy it can lead to systemic risk regime.

Quantification of in vitro replication kinetics of Alagoas vesiculovirus isolates by digital droplet RT-PCR.

Vesicular stomatitis caused by Alagoas vesiculovirus (VSAV) has generated disease outbreaks in Brazil, mainly in the northeast region. Phylogenetic studies divide the isolates into three distinct genotypes (A, B, and C). However, there is no description of how this genetic divergence reflects on the phenotype of VSAV isolates such as in vitro replication fitness. Therefore, the objective of this work was to evaluate the ability of three distinct genotypes of Brazilian isolates of VSAV to grow in different cell-culture lines (BHK-21, Vero, and NCI-H1299). Quantification of viral RNA was performed using RT-PCR digital droplet from supernatant of cell culture collected every 4 h for a period of 24 h of viral growth in three different cell lines (BHK-21, Vero, and NCI-H1299). It was observed that the genotype C isolate has the lowest replication efficiency among the three analyzed viruses, without major changes in the copies of viral RNA over the entire time of the study.

Chetomin, a SARS-CoV-2 3C-like Protease (3CLpro) Inhibitor: In Silico Screening, Enzyme Docking, Molecular Dynamics and Pharmacokinetics Analysis.

The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 6 million deaths. The 3C-like protease (3CLpro) enzyme of the SARS-CoV-2 virus is an attractive druggable target for exploring therapeutic drug candidates to combat COVID-19 due to its key function in viral replication. Marine natural products (MNPs) have attracted considerable attention as alternative sources of antiviral drug candidates. In looking for potential 3CLpro inhibitors, the MNP database (>14,000 molecules) was virtually screened against 3CLpro with the assistance of molecular docking computations. The performance of AutoDock and OEDocking software in anticipating the ligand-3CLpro binding mode was first validated according to the available experimental data. Based on the docking scores, the most potent MNPs were further subjected to molecular dynamics (MD) simulations, and the binding affinities of those molecules were computed using the MM-GBSA approach. According to MM-GBSA//200 ns MD simulations, chetomin (UMHMNP1403367) exhibited a higher binding affinity against 3CLpro than XF7, with ΔGbinding values of -55.5 and -43.7 kcal/mol, respectively. The steadiness and tightness of chetomin with 3CLpro were evaluated, revealing the high stabilization of chetomin (UMHMNP1403367) inside the binding pocket of 3CLpro throughout 200 ns MD simulations. The physicochemical and pharmacokinetic features of chetomin were also predicted, and the oral bioavailability of chetomin was demonstrated. Furthermore, the potentiality of chetomin analogues -namely, chetomin A-D- as 3CLpro inhibitors was investigated. These results warrant further in vivo and in vitro assays of chetomin (UMHMNP1403367) as a promising anti-COVID-19 drug candidate.

The Staphylococcus aureus protein IsdA increases SARS CoV-2 replication by modulating JAK-STAT signaling

The Severe Acute Respiratory Syndrome Coronavirus 2 (CoV-2) pandemic has affected millions globally. A significant complication of CoV-2 infection is secondary bacterial co-infection, as seen in approximately 25% of severe cases. The most common organism isolated during co-infection is Staphylococcus aureus. Here, we describe the development of an invitro co-infection model where both viral and bacterial replication kinetics may be examined. We demonstrate CoV-2 infection does not alter bacterial interactions with host epithelial cells. In contrast, S.aureus enhances CoV-2 replication by 10- to 15-fold. We identify this pro-viral activity is due to the S.aureus iron-regulated surface determinant A (IsdA) protein and demonstrate IsdA modifies host transcription. We find that IsdA alters Janus Kinase- Signal Transducer and Activator of Transcription (JAK-STAT) signaling, by affecting JAK2-STAT3 levels, ultimately leading to increased viral replication. These findings provide key insight into the molecular interactions between host cells, CoV-2 and S.aureus during co-infection.

On the adoption of nonpharmaceutical interventions during the pandemic: An evolutionary game model.

The adoption of behavioral nonpharmaceutical interventions (NPIs) among the public is essential for tackling the COVID-19 pandemic, yet presents challenges due to the complexity of human behaviors. A large body of literature has utilized classic game theory to investigate the population's decisions regarding the adoption of interventions, where the static solution concept such as the Nash equilibrium is studied. However, individual adoption behavior is not static, instead it is a dynamic process that involves the strategic interactions with other counterparts over time. The study of quantitatively analyzing the dynamics on precautionary behavior during an outbreak is rather scarce. This article fills the research gap by developing an evolutionary game-theoretic framework to model the dynamics of population behavior on the adoption of NPI. We construct the two-group asymmetric game, where behavioral change for each group is characterized by replicator equations. Sensitivity analyses are performed to examine the long-term stability of equilibrium points with respect to perturbation of model parameters. We found that the limiting behavior of intervention adoption in the population consists of only pure strategies in a game setting, indicating that the evolutionary outcome is that everyone either takes up the preventive measure or not. We also applied the framework to examine the mask-wearing behavior, and validated with actual data. Overall, this article provides insights into population dynamics on the adoption of intervention strategy during the outbreak, which can be beneficial for policy makers to better understand the evolutionary trajectory of populationbehavior.

RIG-I and MDA5 are modulated by bone morphogenetic protein (BMP6) and are essential for restricting Zika virus infection in human Sertoli cells.

Sexual transmission of Zika virus (ZIKV) is associated with virus persistence in the testes and shedding in the seminal fluid for months after recovery. We previously demonstrated that ZIKV can establish long-term replication without causing cytotoxicity in human Sertoli cells (SC), responsible for maintaining the immune privileged compartment of seminiferous tubules. Functional gene expression analyses also predicted activation of multiple virus sensing pathways including TLR3, RIG-I, and MDA5. Here, we elucidated which of the RNA virus sensing receptors play a decisive role in restricting ZIKV replication. We show that both poly I:C and IFN-β treatment induced a robust antiviral state and reduced ZIKV replication significantly, suggesting that virus sensing and antiviral signaling are functional in SC. Silencing of TLR3, 7, and 9 did not affect virus replication kinetics; however, both RIG-I and MDA5 played a synergistic role in inducing an anti-ZIKV response. Further, the impact of SC-specific immunosuppressive pathways that collectively regulate SC function, specifically the TGF-β superfamily members, TGF-β, Activin A, and BMP6, on ZIKV replication was investigated. While ZIKV did not modulate the expression of TGF-β and Activin A, BMP6 signaling was suppressed at later stages of infection. Notably, treatment with BMP6 increased IFN-β, p-IRF3, and p-STAT1 levels, and expression of key interferon-stimulated genes including MDA5, suggesting that BMP6 enhances antiviral response in SC. Collectively, this study further delineates the key role of the RIG-I-like receptors in sensing ZIKV in SC, and reveals a novel role of BMP6 in modulating innate immune and antiviral response in the testes.

Post-Translation Modifications and Mutations of Human Linker Histone Subtypes: Their Manifestation in Disease.

Linker histones (LH) are a critical component of chromatin in addition to the canonical histones (H2A, H2B, H3, and H4). In humans, 11 subtypes (7 somatic and 4 germinal) of linker histones have been identified, and their diverse cellular functions in chromatin structure, DNA replication, DNA repair, transcription, and apoptosis have been explored, especially for the somatic subtypes. Delineating the unique role of human linker histone (hLH) and their subtypes is highly tedious given their high homology and overlapping expression patterns. However, recent advancements in mass spectrometry combined with HPLC have helped in identifying the post-translational modifications (PTMs) found on the different LH subtypes. However, while a number of PTMs have been identified and their potential nuclear and non-nuclear functions explored in cellular processes, there are very few studies delineating the direct relevance of these PTMs in diseases. In addition, recent whole-genome sequencing of clinical samples from cancer patients and individuals afflicted with Rahman syndrome have identified high-frequency mutations and therefore broadened the perspective of the linker histone mutations in diseases. In this review, we compile the identified PTMs of hLH subtypes, current knowledge of the relevance of hLH PTMs in human diseases, and the correlation of PTMs coinciding with mutations mapped in diseases.

Interdependent progression of bidirectional sister replisomes in E. coli.

Bidirectional DNA replication complexes initiated from the same origin remain colocalized in a factory configuration for part or all their lifetimes. However, there is little evidence that sister replisomes are functionally interdependent, and the consequence of factory replication is unknown. Here, we investigated the functional relationship between sister replisomes in Escherichia coli, which naturally exhibits both factory and solitary configurations in the same replication cycle. Using an inducible transcription factor roadblocking system, we found that blocking one replisome caused a significant decrease in overall progression and velocity of the sister replisome. Remarkably, progression was impaired only if the block occurred while sister replisomes were still in a factory configuration - blocking one fork had no significant effect on the other replisome when sister replisomes were physically separate. Disruption of factory replication also led to increased fork stalling and requirement of fork restart mechanisms. These results suggest that physical association between sister replisomes is important for establishing an efficient and uninterrupted replication program. We discuss the implications of our findings on mechanisms of replication factory structure and function, and cellular strategies of replicating problematic DNA such as highly transcribed segments.

PSMB1 Inhibits the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Recruiting NBR1 To Degrade Nonstructural Protein 12 by Autophagy.

The nonstructural proteins (Nsps) of porcine reproductive and respiratory syndrome virus (PRRSV) play essential roles in virus replication-a multistep process that requires the participation of host factors. It is of great significance for the development of antiviral drugs to characterize the host proteins that interact with PRRSV Nsps and their functions in PRRSV replication. Here, we determined that proteasome subunit β type 1 (PSMB1) interacted with viral Nsp12 to inhibit PRRSV replication in target and permissive cells. PSMB1 could be downregulated by PRRSV infection through interaction with the transcription factor EBF1. Proteasome and autophagy inhibitor assays showed that PSMB1 was regulated by the autophagic pathway to degrade Nsp12. Cotransfection of PSMB1 and Nsp12 increased the level of intracellular autophagy; both molecules were colocated in lysosomes. We also found that the selective autophagy cargo receptor protein NBR1 and E3 ubiquitin ligase STUB1 interacted with PSMB1 and Nsp12, respectively, in the autophagic degradation of Nsp12. Furthermore, the degradation of Nsp12 by PSMB1 was mainly dependent on the ubiquitination of Nsp12 at lysine site 130. Our results indicate for the first time that PSMB1 is an anti-PRRSV host protein that inhibits the replication of PRRSV by degradation of Nsp12 through the selective autophagy pathway. IMPORTANCE PRRS is a major threat to the global pig industry and urgently requires an effective and sustainable control strategy. PRRSV Nsps have important roles in viral RNA synthesis, proteinase activity, induction of replication-associated membrane rearrangements, replicative endoribonuclease activity, determination of virulence, and regulation of host immune response. Research associated with PRRSV Nsps can provide vital guidance to modify the PRRSV genome through reverse genetics in the development of vaccines and diagnostics. The function of Nsp12, which generally plays essential roles in virus replication, remains unclear. We demonstrated that PSMB1 interacted with and degraded Nsp12 through an autophagic pathway to inhibit PRRSV replication. Our data confirmed a novel antiviral function of PSMB1 and allowed us to elaborate on the roles of Nsp12 in PRRSV pathogenesis. These findings suggest a valid and highly conserved candidate target for the development of novel therapies and more effective vaccines and demonstrate the complex cross talk between selective autophagy and PRRSV infection.

Prediction of groundwater pollution diffusion path based on multi-source data fusion

In order to improve the prediction accuracy of groundwater pollution diffusion path, this paper combines multivariate data fusion technology to predict and analyze the groundwater pollution diffusion path. Under the special two-strategy swarm game model of water pollution particle swarm, this paper introduces replication dynamics with bounded continuous time-delay. Moreover, considering the dynamic behavior in both cases of constant kernel function and exponential kernel function, the hawk-dove game model is a special case of the model we are discussing. In addition, this paper proposes a method combining leaching surface and flux concentration, and applies numerical simulation method to simulate and analyze transient leakage monitoring of similar point and line source pollution in planar two-dimensional heterogeneous aquifers. The experimental study verifies that the multivariate data fusion proposed in this paper can play an important role in the prediction of groundwater pollution diffusion path.

Resource Concentration and Clustering in Replicator Dynamics with Stochastic Reset Events

As a model for economic and ecological systems, replicator dynamics represent a basic form of agent competition for finite resources. Here, we investigate the effects of stochastic resetting in this kind of processes. Random reset events abruptly lead individual resources to a small value from which dynamics must start anew. Numerical results show that resource distribution over the population of competing agents develops highly nonuniform profiles, exhibiting clustering and fluctuations with anomalous dependence on the population size. This non-standard statistical behavior jeopardizes an analytical treatment based on mean-field assumptions. We propose alternative simplified analytical approaches which provide a stylized description of entropy evolution for the clustered distribution of resources and explain the unusually slow decrease of fluctuations.

Population games with replicator dynamics under event-triggered payoff provider and a demand response application

We consider a large population of decision makers that choose their evolutionary strategies based on simple pairwise imitation rules. We describe such a dynamic process by the replicator dynamics. Differently from the available literature, where the payoffs signals are assumed to be updated continuously, we consider a more realistic scenario where they are updated occasionally. Our main technical contribution is to devise two event-triggered communication schemes with asymptotic convergence guarantees to a Nash equilibrium. Finally, we show how our proposed approach is applicable as an efficient distributed demand response mechanism.