Bulletin of Mathematical Biology最新文献_第4页

Unveiling the Negative Synergistic Effect of Wall Shear Stress and Insulin on Endothelial NO Dynamics by Mathematical Modeling. 通过数学模型揭示壁剪应力和胰岛素对内皮NO动力学的负协同作用。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-19 DOI: 10.1007/s11538-025-01424-2

Yu-Yuan Zhang, Yong-Jiang Li, Xu-Qu Hu, Chun-Dong Xue, Shen Li, Zheng-Nan Gao, Kai-Rong Qin

{"title":"Unveiling the Negative Synergistic Effect of Wall Shear Stress and Insulin on Endothelial NO Dynamics by Mathematical Modeling.","authors":"Yu-Yuan Zhang, Yong-Jiang Li, Xu-Qu Hu, Chun-Dong Xue, Shen Li, Zheng-Nan Gao, Kai-Rong Qin","doi":"10.1007/s11538-025-01424-2","DOIUrl":"10.1007/s11538-025-01424-2","url":null,"abstract":"Diabetic vascular complications (DVCs) are diabetes-induced vascular dysfunction and pathologies, leading to the major causes of morbidity and mortality in millions of diabetic patients worldwide. DVCs are provoked by endothelial dysfunction which is closely coordinated with two important hallmarks: one is the insufficient insulin secretion or insulin resistance, and another is the decrease in intracellular nitric oxide (NO) influenced by dynamic wall shear stress (WSS). Although the intracellular NO dynamics in endothelial cells (ECs) is crucial for endothelial function, the regulation of NO production by dynamic WSS and insulin is still poorly understood. In this study, we have proposed a mathematical model of intracellular NO production in ECs under the stimulation of dynamic WSS combined with insulin. The model integrates simultaneously the biochemical signaling pathways of insulin and the mechanotransduction pathways induced by dynamic WSS. The accuracy and reliability of the model to quantitatively describe NO production in ECs were compared and validated with reported experimental data. According to the validated model, inhibition of protein kinase B (AKT) phosphorylation and Ca2+ influx by dynamic oscillatory WSS disrupts the dual nature of endothelial nitric oxide synthase (eNOS) enzyme activation. This disruption leads to the decrease in NO production and the bimodal disappearance of NO waveforms. Moreover, the results reveal that dynamic WSS combined with insulin promote endothelial NO production through negative synergistic effects, which is resulted from the temporal differences in mechanical and biochemical signaling. In brief, the proposed model elucidates the mechanism of NO generation activated by dynamic WSS combined with insulin, providing a potential target and theoretical framework for future treatment of DVCs.","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 4","pages":"46"},"PeriodicalIF":2.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Combining Mechanisms of Growth Arrest in Solid Tumours: A Mathematical Investigation. 修正：实体肿瘤生长阻滞的综合机制：一项数学研究。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-12 DOI: 10.1007/s11538-024-01382-1

Chloé Colson, Helen M Byrne, Philip K Maini

引用次数: 0

A Simple Framework for Agent-Based Modeling with Extracellular Matrix. 基于细胞外基质的代理建模的简单框架

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-12 DOI: 10.1007/s11538-024-01408-8

John Metzcar, Ben S Duggan, Brandon Fischer, Matthew Murphy, Randy Heiland, Paul Macklin

{"title":"A Simple Framework for Agent-Based Modeling with Extracellular Matrix.","authors":"John Metzcar, Ben S Duggan, Brandon Fischer, Matthew Murphy, Randy Heiland, Paul Macklin","doi":"10.1007/s11538-024-01408-8","DOIUrl":"10.1007/s11538-024-01408-8","url":null,"abstract":"Extracellular matrix (ECM) is a key component of the cellular microenvironment and critical in multiple disease and developmental processes. Representing ECM and cell-ECM interactions is a challenging multiscale problem as they span molecular-level details to tissue-level dynamics. While several computational frameworks exist for ECM modeling, they often focus on very detailed modeling of individual ECM fibers or represent only a single aspect of the ECM. Using the PhysiCell agent-based modeling platform, we developed a framework of intermediate detail with the ability to capture bidirectional cell-ECM interactions. We represent a small region of ECM, an ECM element, with three variables describing its local microstructure: anisotropy, density, and overall fiber orientation. To spatially model the ECM, we use an array of ECM elements. Cells remodel local ECM microstructure and in turn, local microstructure impacts cellular motility. We demonstrate the utility of this framework and reusability of its core cell-ECM interaction model through examples in cellular invasion, wound healing, basement membrane degradation, and leader-follower collective migration. Despite the relative simplicity of the framework, it is able to capture a broad range of cell-ECM interactions of interest to the modeling community. Furthermore, variables representing the ECM microstructure are accessible through simple programming interfaces. This allows them to impact cell behaviors, such as proliferation and death, without requiring custom code for each interaction, particularly through PhysiCell's modeling grammar, enabling rapid modeling of a diverse range of cell-matrix biology. We make this framework available as a free and open source software package at https://github.com/PhysiCell-Models/collective-invasion .","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 3","pages":"43"},"PeriodicalIF":2.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Simplifying and Characterizing DAGs and Phylogenetic Networks via Least Common Ancestor Constraints. 通过最小共同祖先约束简化和表征dag和系统发育网络。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-12 DOI: 10.1007/s11538-025-01419-z

Anna Lindeberg, Marc Hellmuth

{"title":"Simplifying and Characterizing DAGs and Phylogenetic Networks via Least Common Ancestor Constraints.","authors":"Anna Lindeberg, Marc Hellmuth","doi":"10.1007/s11538-025-01419-z","DOIUrl":"10.1007/s11538-025-01419-z","url":null,"abstract":"Rooted phylogenetic networks, or more generally, directed acyclic graphs (DAGs), are widely used to model species or gene relationships that traditional rooted trees cannot fully capture, especially in the presence of reticulate processes or horizontal gene transfers. Such networks or DAGs are typically inferred from observable data (e.g., genomic sequences of extant species), providing only an estimate of the true evolutionary history. However, these inferred DAGs are often complex and difficult to interpret. In particular, many contain vertices that do not serve as least common ancestors (LCAs) for any subset of the underlying genes or species, thus may lack direct support from the observable data. In contrast, LCA vertices are witnessed by historical traces justifying their existence and thus represent ancestral states substantiated by the data. To reduce unnecessary complexity and eliminate unsupported vertices, we aim to simplify a DAG to retain only LCA vertices while preserving essential evolutionary information. In this paper, we characterize <math><mtext>LCA</mtext></math> -relevant and <math><mtext>lca</mtext></math> -relevant DAGs, defined as those in which every vertex serves as an LCA (or unique LCA) for some subset of taxa. We introduce methods to identify LCAs in DAGs and efficiently transform any DAG into an <math><mtext>LCA</mtext></math> -relevant or <math><mtext>lca</mtext></math> -relevant one while preserving key structural properties of the original DAG or network. This transformation is achieved using a simple operator \" <math><mo>⊖</mo></math> \" that mimics vertex suppression.","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 3","pages":"44"},"PeriodicalIF":2.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11821803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Non-linear Interaction Between Oxygen and Lactate on Solid Tumor Growth Under Cyclic Hypoxia. 循环缺氧条件下氧与乳酸非线性交互作用对实体瘤生长的影响。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-11 DOI: 10.1007/s11538-025-01420-6

Gopinath Sadhu, D C Dalal

{"title":"Effects of Non-linear Interaction Between Oxygen and Lactate on Solid Tumor Growth Under Cyclic Hypoxia.","authors":"Gopinath Sadhu, D C Dalal","doi":"10.1007/s11538-025-01420-6","DOIUrl":"10.1007/s11538-025-01420-6","url":null,"abstract":"Oxygen is a crucial element for cellular respiration. Based on oxygen concentration, tumor regions can be categorized as normoxic, hypoxic, and necrotic. Hypoxic tumor cells switch their metabolism from aerobic glycolysis to anaerobic glycolysis. As a result, lactate is produced in hypoxic regions and is used as an alternative metabolic fuel by normoxic tumor cells. The consumption of lactate and oxygen by tumor cells does not follow a linear pattern. Scientific studies suggest that oxygen consumption and lactate production are non-linear phenomena. In this study, we propose a two-dimensional mathematical model to investigate lactate dynamics in avascular tumors with various initial shapes, such as circular, elliptical, and petal, and to explore its growth patterns in the context of non-linear interactions between oxygen and lactate. In certain human tumors, particularly in kidney, skin, and liver, multiple tumors may emerge within a tissue domain simultaneously. We also examine how the growth patterns of multiple tumors evolve within a shared domain. Cyclic hypoxia, commonly observed in solid tumors, results from oxygen fluctuations over time at the tumor site. Additionally, we analyze lactate dynamics and tumor growth patterns in environments with cyclic hypoxia. In order to simulate the proposed model, we use finite element based COMSOL Multiphysics 6.0 interface. The simulated results show excellent agreement with experimental data. Our findings reveal that the initial tumor shape significantly influences the lactate distribution and the tumor's internal structure. Furthermore, the simulations indicate that multiple tumors eventually merge into a single tumor. We also observe that cyclic hypoxia with short periodicity increases tumor volume.","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 3","pages":"41"},"PeriodicalIF":2.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mathematical Model of CAR T-Cell Therapy for a B-Cell Lymphoma Lymph Node. CAR - t细胞治疗b细胞淋巴瘤淋巴结的数学模型。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-07 DOI: 10.1007/s11538-025-01417-1

Soukaina Sabir, Odelaisy León-Triana, Sergio Serrano, Roberto Barrio, Victor M Pérez-García

引用次数: 0

Employing Observability Rank Conditions for Taking into Account Experimental Information a priori. 利用可观察性秩条件考虑先验实验信息。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-06 DOI: 10.1007/s11538-025-01415-3

Alejandro F Villaverde

{"title":"Employing Observability Rank Conditions for Taking into Account Experimental Information a priori.","authors":"Alejandro F Villaverde","doi":"10.1007/s11538-025-01415-3","DOIUrl":"10.1007/s11538-025-01415-3","url":null,"abstract":"The concept of identifiability describes the possibility of inferring the parameters of a dynamic model by observing its output. It is common and useful to distinguish between structural and practical identifiability. The former property is fully determined by the model equations, while the latter is also influenced by the characteristics of the available experimental data. Structural identifiability can be determined by means of symbolic computations, which may be performed before collecting experimental data, and are hence sometimes called a priori analyses. Practical identifiability is typically assessed numerically, with methods that require simulations-and often also optimization-and are applied a posteriori. An approach to study structural local identifiability is to consider it as a particular case of observability, which is the possibility of inferring the internal state of a system from its output. Thus, both properties can be analysed jointly, by building a generalized observability matrix and computing its rank. The aim of this paper is to investigate to which extent such observability-based methods can also inform about practical aspects related with the experimental setup, which are usually not approached in this way. To this end, we explore a number of possible extensions of the rank tests, and discuss the purposes for which they can be informative as well as others for which they cannot.","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 3","pages":"39"},"PeriodicalIF":2.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differentiating Contact with Symptomatic and Asymptomatic Infectious Individuals in a SEIR Epidemic Model. SEIR流行病模型中区分有症状和无症状感染个体的接触

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-02-04 DOI: 10.1007/s11538-025-01416-2

Victoria Chebotaeva, Anish Srinivasan, Paula A Vasquez

引用次数: 0

Evolution of Human Pair Bonds as a Consequence of Male-Biased Mating Sex Ratios? 人类伴侣关系的进化是男性偏好的交配性别比例的结果？

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-01-30 DOI: 10.1007/s11538-025-01414-4

Matthew C Nitschke, Viney Kumar, Katrina E Milliner, Kristen Hawkes, Peter S Kim

{"title":"Evolution of Human Pair Bonds as a Consequence of Male-Biased Mating Sex Ratios?","authors":"Matthew C Nitschke, Viney Kumar, Katrina E Milliner, Kristen Hawkes, Peter S Kim","doi":"10.1007/s11538-025-01414-4","DOIUrl":"10.1007/s11538-025-01414-4","url":null,"abstract":"Compared to our closest primate relatives, human life history involves greater longevity, which includes a distinctive postmenopausal life stage. Given mammalian reproductive physiology in which females build a finite stock of cells that can become oocytes early in life, which then continuously deplete mostly through cell death while males produce new sperm throughout adulthood, the postmenopausal stage makes the sex ratio in the fertile pool, called the adult sex ratio (ASR), male biased. Additionally, this affects a more fine-grained ratio, the operational sex ratio (OSR), defined as the ratio of males to females currently able to conceive. Here, we construct an ODE model in which males compete for paternities using either a multiple-mating or mate-guarding strategy. Our focus is on investigating the differences of strategy choice between populations with varying life histories, which include a distinct post-fertile stage for adult females. By simulating the system, we determine the dominant strategy and its dependence on various parameter combinations. Our results show that an increase in OSR and ASR correlates well with a change in the dominant strategy from multiple mating to guarding.","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 3","pages":"37"},"PeriodicalIF":2.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adaptive Immunity Determines the Cancer Treatment Outcome of Oncolytic Virus and Anti-PD-1. 适应性免疫决定溶瘤病毒和抗pd -1治疗癌症的效果。

IF 2 4区数学

Bulletin of Mathematical Biology Pub Date : 2025-01-29 DOI: 10.1007/s11538-025-01413-5

Kang-Ling Liao, Kenton D Watt

{"title":"Adaptive Immunity Determines the Cancer Treatment Outcome of Oncolytic Virus and Anti-PD-1.","authors":"Kang-Ling Liao, Kenton D Watt","doi":"10.1007/s11538-025-01413-5","DOIUrl":"10.1007/s11538-025-01413-5","url":null,"abstract":"The immune checkpoint inhibitor, anti-programmed death protein-1 (anti-PD-1), enhances adaptive immunity to kill tumor cells, and the oncolytic virus (OV) triggers innate immunity to clear the infected tumor cells. We create a mathematical model to investigate how the interaction between adaptive and innate immunities under OV and anti-PD-1 affects tumor reduction. For different immunity strength, we create the corresponding virtual baseline patients and cohort patients to decipher the major factors determining the treatment outcome. Global sensitivity analysis indicates that adaptive immunity has more control on the treatment outcome than innate immunity, and whether anti-PD-1 cancels out the OV treatment efficacy depends on the OV dosage and the balance between clearance of infected tumor cells and OV by T cells. The optimal OV infection rate and dosage suggest that OV treatment is more sensitive to adaptive immunity than innate immunity. Our model prediction also indicates that tumor reduction is more sensitive to anti-PD-1 efficacy as adaptive immunity becomes stronger, and anti-PD-1 trends to cancel out the OV treatment efficacy as innate immunity becomes stronger. Based on these results, the recommended treatment protocol for patients with different immunity strength can be determined.","PeriodicalId":9372,"journal":{"name":"Bulletin of Mathematical Biology","volume":"87 3","pages":"36"},"PeriodicalIF":2.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0