643 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

    Consideration of the bioavailability of metal/metalloid species in freshwaters: experiences regarding the implementation of biotic ligand model-based approaches in risk assessment frameworks

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    After the scientific development of Biotic Ligand Models (BLMs) in recent decades these models are now considered suitable for implementation in regulatory risk assessment of metals in freshwater bodies. The approach has been developed over several years and has been described in many peer-reviewed publications. The original complex BLMs have been applied in prospective risk assessment reports for metals and metal compounds and are also recommended as suitable concepts for the evaluation of monitoring data in the context of the European Water Framework Directive. Currently, several user-friendly BLM-based bioavailability software tools are available for assessing the aquatic toxicity of a limited number of metals (mainly copper, nickel, and zinc). These tools need only a basic set of water parameters as input (e.g., pH, hardness, dissolved organic matter and dissolved metal concentration). Such tools seem appropriate to foster the implementation in routine water quality assessments. This work aims to review the existing bioavailability-based regulatory approaches and the application of available BLM-based bioavailability tools for this purpose. Advantages and possible drawbacks of these tools (e.g., feasibility, boundaries of validity) are discussed, and recommendations for further implementation are given

    Supporting Parental Decisions About Genomic Sequencing for Newborn Screening: The NC NEXUS Decision Aid

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    Advances in genomic sequencing technology have raised fundamental challenges to the traditional ways genomic information is communicated. These challenges will become increasingly complex and will affect a much larger population in the future if genomics is incorporated into standard newborn screening practice. Clinicians, public health officials, and other stakeholders will need to agree on the types of information that they should seek and communicate to parents. Currently, few evidence-based and validated tools are available to support parental informed decision-making. These tools will be necessary as genomics is integrated into clinical practice and public health systems. In this article we describe how the North Carolina Newborn Exome Sequencing for Universal Screening study is addressing the need to support parents in making informed decisions about the use of genomic testing in newborn screening. We outline the context for newborn screening and justify the need for parental decision support. We also describe the process of decision aid development and the data sources, processes, and best practices being used in development. By the end of the study, we will have an evidenced-based process and validated tools to support parental informed decision-making about the use of genomic sequencing in newborn screening. Data from the study will help answer important questions about which genomic information ought to be sought and communicated when testing newborns

    Synthesis, characterization, and biological evaluation of N-methyl derivatives of norbelladine

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    Abstract Norbelladine derivatives have garnered attention in recent years due to their diverse biological activities and pivotal role in the biosynthetic pathway of Amaryllidaceae alkaloids. This study reports the synthesis and biological evaluation of four O,N-methylated derivatives of norbelladine. These derivatives were synthesized through a three-step process: forming imine intermediates from benzaldehydes with tyramine, hydrogenating them to secondary amines, and N-methylating these amines. The products were purified and characterized by 1H and 13C NMR spectroscopy. Their biological activities were assessed by evaluating their ability to inhibit Alzheimer’s disease-related enzymes acetylcholinesterase and butyrylcholinesterase. Additionally, the cytotoxic activity of the novel derivatives was tested against cancer cell lines derived from hepatocarcinoma (Huh7), adenocarcinoma (HCT-8), and acute myeloid leukemia (THP-1) cells, and their antiviral properties against a human coronavirus (HCoV-OC43), a flavivirus (dengue virus), and a lentivirus (pseudotyped HIV-1). Docking analysis was performed to understand the impact of the N-methylation on their pharmacological relevance. The results indicate that while N-methylation does not significantly affect antiviral activity, it enhances butyrylcholinesterase inhibition for N-methylnorbelladine and 4′-O,N-dimethylnorbelladine. Overall, this work enhances our understanding of norbelladine derivatives, provides new tools for Alzheimer’s disease research, and lays the groundwork for future pharmaceutical developments

    Intestinal Resident Yeast Candida glabrata Requires Cyb2p-Mediated Lactate Assimilation to Adapt in Mouse Intestine

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    The intestinal resident Candida glabrata opportunistically infects humans. However few genetic factors for adaptation in the intestine are identified in this fungus. Here we describe the C. glabrata CYB2 gene encoding lactate dehydrogenase as an adaptation factor for survival in the intestine. CYB2 was identified as a virulence factor by a silkworm infection study. To determine the function of CYB2, we analysed in vitro phenotypes of the mutant Δcyb2. The Δcyb2 mutant grew well in glucose medium under aerobic and anaerobic conditions, was not supersensitive to nitric oxide which has fungicidal-effect in phagocytes, and had normal levels of general virulence factors protease, lipase and adherence activities. A previous report suggested that Cyb2p is responsible for lactate assimilation. Additionally, it was speculated that lactate assimilation was required for Candida virulence because Candida must synthesize glucose via gluconeogenesis under glucose-limited conditions such as in the host. Indeed, the Δcyb2 mutant could not grow on lactate medium in which lactate is the sole carbon source in the absence of glucose, indicating that Cyb2p plays a role in lactate assimilation. We hypothesized that Cyb2p-mediated lactate assimilation is necessary for proliferation in the intestinal tract, as the intestine is rich in lactate produced by bacteria flora, but not glucose. The Δcyb2 mutant showed 100-fold decreased adaptation and few cells of Saccharomyces cerevisiae can adapt in mouse ceca. Interestingly, C. glabrata could assimilate lactate under hypoxic conditions, dependent on CYB2, but not yeast S. cerevisiae. Because accessible oxygen is limited in the intestine, the ability for lactate assimilation in hypoxic conditions may provide an advantage for a pathogenic yeast. From those results, we conclude that Cyb2p-mediated lactate assimilation is an intestinal adaptation factor of C. glabrata
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