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Free, publicly-accessible full text available December 1, 2025
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Abstract Glioblastoma (GBM) is an aggressive primary brain cancer that currently has minimally effective treatments. Like other cancers, immunosuppression by the PD-L1-PD-1 immune checkpoint complex is a prominent axis by which glioma cells evade the immune system. Myeloid-derived suppressor cells (MDSCs), which are recruited to the glioma microenviroment, also contribute to the immunosuppressed GBM microenvironment by suppressing T cell functions. In this paper, we propose a GBM-specific tumor-immune ordinary differential equations model of glioma cells, T cells, and MDSCs to provide theoretical insights into the interactions between these cells. Equilibrium and stability analysis indicates that there are unique tumorous and tumor-free equilibria which are locally stable under certain conditions. Further, the tumor-free equilibrium is globally stable when T cell activation and the tumor kill rate by T cells overcome tumor growth, T cell inhibition by PD-L1-PD-1 and MDSCs, and the T cell death rate. Bifurcation analysis suggests that a treatment plan that includes surgical resection and therapeutics targeting immune suppression caused by the PD-L1-PD1 complex and MDSCs results in the system tending to the tumor-free equilibrium. Using a set of preclinical experimental data, we implement the approximate Bayesian computation (ABC) rejection method to construct probability density distributions that estimate model parameters. These distributions inform an appropriate search curve for global sensitivity analysis using the extended fourier amplitude sensitivity test. Sensitivity results combined with the ABC method suggest that parameter interaction is occurring between the drivers of tumor burden, which are the tumor growth rate and carrying capacity as well as the tumor kill rate by T cells, and the two modeled forms of immunosuppression, PD-L1-PD-1 immune checkpoint and MDSC suppression of T cells. Thus, treatment with an immune checkpoint inhibitor in combination with a therapeutic targeting the inhibitory mechanisms of MDSCs should be explored.more » « less
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The May–Leonard model was introduced to examine the behavior of three competing populations where rich dynamics, such as limit cycles and nonperiodic cyclic solutions, arise. In this work, we perturb the system by adding the capability of global mutations, allowing one species to evolve to the other two in a linear manner. We find that for small mutation rates, the perturbed system not only retains some of the dynamics seen in the classical model, such as the three-species equal-population equilibrium bifurcating to a limit cycle, but also exhibits new behavior. For instance, we capture curves of fold bifurcations where pairs of equilibria emerge and then coalesce. As a result, we uncover parameter regimes with new types of stable fixed points that are distinct from the single- and dual-population equilibria characteristic of the original model. On the contrary, the linearly perturbed system fails to maintain heteroclinic connections that exist in the original system. In short, a linear perturbation proves to be significant enough to substantially influence the dynamics, even with small mutation rates.more » « less
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Navigating a career as a mathematician in academia, industry, or a national lab was challenging for many families with children before the COVID-19 pandemic. Then, the pandemic hit and the situation was exacerbated. Parents and parents-to-be were tested and challenged in ways unanticipated, with time for parental duties clashing with time for research, teaching, and service, leaving those wishing to be parents contemplating the feasibility of this balancing act of parenthood and work-life in a COVID-19 era and beyond. Many members in our mathematics community experienced these challenges first hand and persevered. Lessons were learned and different methodologies employed as many reimagined what work-life and home-life balance looked like. These lessons and methodologies can be useful in our future endeavors as parent-educators and researchers, and if shared can benefit others who are in parenthood or on the path to parenthood, as they seek to create a better harmony between work and home life. Thus, this article explores and showcases some of the discussions that ensued during a 2022 Joint Mathematics Meeting (JMM) Professional Development Workshop Mathematicians Navigating Parenthood organized by the authors. The article collects key discussion points and lessons learned, putting together useful solutions and resources, as well as unresolved questions. We report on strategies to help parents and parents-to-be succeed as well as present proposals on what departments could implement based on their individual policies to provide a welcoming environment to colleagues with, or expecting, children.more » « less
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null (Ed.)Male and female moths communicate in complex ways to search for and to select a mate. In a process termed calling, females emit small quantities of pheromones, generating plumes that spread in the environment. Males detect the plume through their antennae and navigate toward the female. The reproductive process is marked by female choice and male–male competition, since multiple males aim to reach the female but only the first can mate with her. This provides an opportunity for female selection on male traits such as chemosensitivity to pheromone molecules and mobility. We develop a mathematical framework to investigate the overall mating likelihood, the mean first arrival time, and the quality of the first male to reach the female for four experimentally observed female calling strategies unfolding over a typical one-week mating period. We present both analytical solutions of a simplified model as well as results from agent-based numerical simulations. Our findings suggest that, by adjusting call times and the amount of released pheromone, females can optimize the mating process. In particular, shorter calling times and lower pheromone titers at onset of the mating period that gradually increase over time allow females to aim for higher-quality males while still ensuring that mating occurs by the end of the mating period.more » « less
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