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Prioritizing cervical cancer candidate genes using chaos game and fractal-based time series approach. 利用混沌博弈和基于分形的时间序列方法确定宫颈癌候选基因的优先顺序
IF 1.3 4区 生物学 Q3 BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-05-28 DOI: 10.1007/s12064-024-00418-3
T Mallikarjuna, N B Thummadi, Vaibhav Vindal, P Manimaran

Cervical cancer is one of the most severe threats to women worldwide and holds fourth rank in lethality. It is estimated that 604, 127 cervical cancer cases have been reported in 2020 globally. With advancements in high throughput technologies and bioinformatics, several cervical candidate genes have been proposed for better therapeutic strategies. In this paper, we intend to prioritize the candidate genes that are involved in cervical cancer progression through a fractal time series-based cross-correlations approach. we apply the chaos game representation theory combining a two-dimensional multifractal detrended cross-correlations approach among the known and candidate genes involved in cervical cancer progression to prioritize the candidate genes. We obtained 16 candidate genes that showed cross-correlation with known cancer genes. Functional enrichment analysis of the candidate genes shows that they involve GO terms: biological processes, cell-cell junction assembly, cell-cell junction organization, regulation of cell shape, cortical actin cytoskeleton organization, and actomyosin structure organization. KEGG pathway analysis revealed genes' role in Rap1 signaling pathway, ErbB signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, Acute myeloid leukemia, chronic myeloid leukemia, Breast cancer, Thyroid cancer, Bladder cancer, and Gastric cancer. Further, we performed survival analysis and prioritized six genes CDH2, PAIP1, BRAF, EPB41L3, OSMR, and RUNX1 as potential candidate genes for cervical cancer that has a crucial role in tumor progression. We found that our study through this integrative approach an efficient tool and paved a new way to prioritize the candidate genes and these genes could be evaluated experimentally for potential validation. We suggest this may be useful in analyzing the nucleotide sequences and protein sequences for clustering, classification, class affiliation, etc.

宫颈癌是全球妇女面临的最严重威胁之一,致死率排名第四。据估计,2020 年全球将报告 604 127 例宫颈癌病例。随着高通量技术和生物信息学的发展,人们提出了一些宫颈癌候选基因,以寻求更好的治疗策略。在本文中,我们打算通过基于分形时间序列的交叉相关方法,对参与宫颈癌进展的候选基因进行优先排序。我们应用混沌博弈表示理论,结合二维多分形去趋势交叉相关方法,对参与宫颈癌进展的已知基因和候选基因进行优先排序。我们获得了 16 个与已知癌基因存在交叉相关性的候选基因。候选基因的功能富集分析表明,它们涉及的GO术语包括:生物过程、细胞-细胞连接组装、细胞-细胞连接组织、细胞形状调控、皮质肌动蛋白细胞骨架组织和肌动蛋白结构组织。KEGG 通路分析显示,基因在 Rap1 信号通路、ErbB 信号通路、MAPK 信号通路、PI3K-Akt 信号通路、mTOR 信号通路、急性髓性白血病、慢性髓性白血病、乳腺癌、甲状腺癌、膀胱癌和胃癌中发挥作用。此外,我们还进行了生存分析,并优先选择了 CDH2、PAIP1、BRAF、EPB41L3、OSMR 和 RUNX1 这六个基因作为宫颈癌的潜在候选基因,这些基因在肿瘤进展中起着至关重要的作用。我们发现,通过这种综合方法,我们的研究成为了一种有效的工具,并为确定候选基因的优先顺序铺平了一条新路。我们认为这可能有助于分析核苷酸序列和蛋白质序列,以进行聚类、分类、隶属类等。
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引用次数: 0
2-Site versus 3-site models of ATP hydrolysis by F1-ATPase: definitive mathematical proof using combinatorics and conservation equations. F1-ATP 酶水解 ATP 的 2 位点模型与 3 位点模型:使用组合学和守恒方程的明确数学证明。
IF 1.3 4区 生物学 Q3 BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-30 DOI: 10.1007/s12064-024-00421-8
Sunil Nath

The F1-ATPase enzyme is the smallest-known molecular motor that rotates in 120° steps, driven by the hydrolysis of ATP. It is a multi-subunit enzyme that contains three catalytic sites. A central question is how the elementary chemical reactions that occur in the three sites are coupled to mechanical rotation. Various models and coupling schemes have been formulated in an attempt to answer this question. They can be classified as 2-site (bi-site) models, exemplified by Boyer's binding change mechanism first proposed 50 years ago, and 3-site (tri-site) models such as Nath's torsional mechanism, first postulated 25 years ago and embellished 1 year back. Experimental data collated using diverse approaches have conclusively shown that steady-state ATP hydrolysis by F1-ATPase occurs in tri-site mode. Hence older models have been continually modified to make them conform to the new facts. Here, we have developed a pure mathematical approach based on combinatorics and conservation laws to test if proposed models are 2-site or 3-site. Based on this novel combinatorial approach, we have proved that older and modified models are effectively bi‒site models in that catalysis and rotation in F1-ATPase occurs in these models with only two catalytic sites occupied by bound nucleotide. Hence these models contradict consensus experimental data. The recent 2023 model of ATP hydrolysis by F1-ATPase has been proved to be a true tri-site model based on our novel mathematical approach. Such pure mathematical proofs constitute an important step forward for ATP mechanism. However, in what must be considered an aspect with great scientific potential, the power of such mathematical proofs has not been fully exploited to solve molecular biological problems, in our opinion. We believe that the creative application of pure mathematical proofs (for another example see Nath in Theory Biosci 141:249-260, 2022) can help resolve with finality various longstanding molecular-level issues that arise as a matter of course in the analysis of fundamental biological problems. Such issues have proved extraordinarily difficult to resolve by standard experimental, theoretical, or computational approaches.

F1-ATPase 酶是已知的最小分子马达,在 ATP 的水解作用驱动下以 120° 的步长旋转。它是一种多亚基酶,包含三个催化位点。一个核心问题是,这三个位点发生的基本化学反应如何与机械旋转耦合。为了回答这个问题,人们提出了各种模型和耦合方案。它们可分为两个位点(双位点)模型和三个位点(三位点)模型,前者如 Boyer 于 50 年前首次提出的结合变化机制,后者如 Nath 于 25 年前首次提出并在 1 年前完善的扭转机制。使用不同方法整理的实验数据已确凿表明,F1-ATP 酶的稳态 ATP 水解发生在三位模式中。因此,人们不断修改旧模型,使其符合新的事实。在此,我们开发了一种基于组合学和守恒定律的纯数学方法,以检验所提出的模型是 2 位还是 3 位。基于这种新颖的组合方法,我们证明了旧模型和修改后的模型实际上是双位点模型,因为在这些模型中,F1-ATPase 的催化和旋转只发生在两个被结合核苷酸占据的催化位点上。因此,这些模型与一致的实验数据相矛盾。根据我们新颖的数学方法,最近关于 F1-ATP 酶水解 ATP 的 2023 模型已被证明是一个真正的三位点模型。这种纯数学证明是 ATP 机理的重要一步。然而,在我们看来,这种纯数学证明在解决分子生物学问题方面还没有充分发挥其巨大的科学潜力。我们相信,创造性地应用纯数学证明(另一个例子见 Nath 在 Theory Biosci 141:249-260, 2022 中的文章)有助于最终解决在分析基本生物问题时理所当然会出现的各种长期存在的分子级问题。事实证明,标准的实验、理论或计算方法很难解决这些问题。
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引用次数: 0
Postmortem communication. 死后交流。
IF 1.3 4区 生物学 Q3 BIOLOGY Pub Date : 2024-09-01 Epub Date: 2024-08-03 DOI: 10.1007/s12064-024-00423-6
Michael Bordonaro

The phenomenon of near death and dying experiences has been both of popular interest and of scientific speculation. However, the reality of mental perception at the point of death is currently a subjective experience and has not been formally evaluated. While postmortem gene expression, even in humans, has been evaluated, restoration of postmortem brain activity has heretofore only been attempted in animal models, at the molecular and cellular levels. Meanwhile, progress has been made to translate brain activity of living humans into speech and images. This paper proposes two inter-related thought experiments. First, assuming progress and refinement of the technology of translating human brain activity into interpretable speech and images, can an objective analysis of death experiences be obtained by utilizing these technologies on dying humans? Second, can human brain function be revived postmortem and, if so, can the relevant technologies be utilized for communication with (recently) deceased individuals? In this paper, these questions are considered and possible implications explored.

濒死和临终体验现象一直受到大众的关注和科学界的猜测。然而,死亡时的精神感知是否真实目前只是一种主观体验,尚未得到正式评估。虽然已经对死后基因表达进行了评估,甚至对人类的死后基因表达也进行了评估,但迄今为止,只有在动物模型中尝试在分子和细胞水平上恢复死后大脑活动。与此同时,将活人的大脑活动转化为语言和图像的工作也取得了进展。本文提出了两个相互关联的思想实验。首先,假设将人类大脑活动转化为可解读的语言和图像的技术取得了进展并不断完善,那么利用这些技术对垂死的人类进行分析,能否获得对死亡经历的客观分析?其次,人脑功能是否可以在死后恢复,如果可以,是否可以利用相关技术与(最近)去世的人进行交流?本文将考虑这些问题,并探讨可能的影响。
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引用次数: 0
Dynamics of neural fields with exponential temporal kernel. 具有指数时间核的神经场动力学。
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-06-01 Epub Date: 2024-03-09 DOI: 10.1007/s12064-024-00414-7
Elham Shamsara, Marius E Yamakou, Fatihcan M Atay, Jürgen Jost

We consider the standard neural field equation with an exponential temporal kernel. We analyze the time-independent (static) and time-dependent (dynamic) bifurcations of the equilibrium solution and the emerging spatiotemporal wave patterns. We show that an exponential temporal kernel does not allow static bifurcations such as saddle-node, pitchfork, and in particular, static Turing bifurcations. However, the exponential temporal kernel possesses the important property that it takes into account the finite memory of past activities of neurons, which Green's function does not. Through a dynamic bifurcation analysis, we give explicit bifurcation conditions. Hopf bifurcations lead to temporally non-constant, but spatially constant solutions, but Turing-Hopf bifurcations generate spatially and temporally non-constant solutions, in particular, traveling waves. Bifurcation parameters are the coefficient of the exponential temporal kernel, the transmission speed of neural signals, the time delay rate of synapses, and the ratio of excitatory to inhibitory synaptic weights.

我们考虑了具有指数时间核的标准神经场方程。我们分析了平衡解与时间无关的(静态)和与时间有关的(动态)分岔以及新出现的时空波形。我们发现,指数时间内核不允许出现静态分岔,如鞍节点、叉形分岔,特别是静态图灵分岔。然而,指数时间核具有一个重要特性,即它考虑到了神经元对过去活动的有限记忆,而格林函数则没有考虑到这一点。通过动态分岔分析,我们给出了明确的分岔条件。霍普夫分岔会产生时间非恒定但空间恒定的解,而图灵-霍普夫分岔则会产生空间和时间非恒定的解,尤其是行波。分岔参数包括指数时间核的系数、神经信号的传输速度、突触的时延率以及兴奋性与抑制性突触权重之比。
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引用次数: 0
The bubble theory: exploring the transition from first replicators to cells and viruses in a landscape-based scenario. 气泡理论:在基于景观的情景中探索从最初的复制者到细胞和病毒的过渡。
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1007/s12064-024-00417-4
Radoslaw W Piast

This study proposes a landscape-based scenario for the origin of viruses and cells, focusing on the adaptability of preexisting replicons from the RNP (ribonucleoprotein) world. The scenario postulates that life emerged in a subterranean "warm little pond" where organic matter accumulated, resulting in a prebiotic soup rich in nucleotides, amino acids, and lipids, which served as nutrients for the first self-replicating entities. Over time, the RNA world, followed by the RNP world, came into existence. Replicators/replicons, along with the nutritious soup from the pond, were washed out into the river and diluted. Lipid bubbles, enclosing organic matter, provided the last suitable environment for replicons to replicate. Two survival strategies emerged under these conditions: cell-like structures that obtained nutrients by merging with new bubbles, and virus-like entities that developed various techniques to transmit themselves to fresh bubbles. The presented hypothesis provides the possibility for the common origin of cells and viruses on rocky worlds hosting liquid water, like Earth.

这项研究为病毒和细胞的起源提出了一种基于地貌的假设,重点是 RNP(核糖核蛋白)世界中预先存在的复制子的适应性。这种假设认为,生命出现在一个地下 "温暖的小池塘 "中,那里积累了大量有机物质,形成了富含核苷酸、氨基酸和脂质的前生物汤,这些物质成为第一批自我复制实体的养分。随着时间的推移,RNA 世界诞生了,随后是 RNP 世界。复制体/复制子与池塘中的营养汤一起被冲入河中,并被稀释。包裹着有机物的脂质气泡为复制子提供了最后的适宜复制环境。在这种情况下,出现了两种生存策略:一种是类似细胞的结构,它们通过与新的气泡融合来获取营养;另一种是类似病毒的实体,它们开发出各种技术,将自身传播到新的气泡中。提出的假设为细胞和病毒共同起源于像地球这样拥有液态水的岩石世界提供了可能。
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引用次数: 0
Behavioral selection in structured populations. 结构化种群中的行为选择。
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-06-01 Epub Date: 2024-03-05 DOI: 10.1007/s12064-024-00413-8
Matthias Borgstede

The multilevel model of behavioral selection (MLBS) by Borgstede and Eggert (Behav Process 186:104370. 10.1016/j.beproc.2021.104370 , 2021) provides a formal framework that integrates reinforcement learning with natural selection using an extended Price equation. However, the MLBS is so far only formulated for homogeneous populations, thereby excluding all sources of variation between individuals. This limitation is of primary theoretical concern because any application of the MLBS to real data requires to account for variation between individuals. In this paper, I extend the MLBS to account for inter-individual variation by dividing the population into homogeneous sub-populations and including class-specific reproductive values as weighting factors for an individual's evolutionary fitness. The resulting formalism closes the gap between the theoretical underpinnings of behavioral selection and the application of the theory to empirical data, which naturally includes inter-individual variation. Furthermore, the extended MLBS is used to establish an explicit connection between the dynamics of learning and the maximization of individual fitness. These results expand the scope of the MLBS as a general theoretical framework for the quantitative analysis of learning and evolution.

Borgstede 和 Eggert 的行为选择多层次模型(MLBS)(Behav Process 186:104370. 10.1016/j.beproc.2021.104370 , 2021)提供了一个正式框架,利用扩展的普赖斯方程将强化学习与自然选择结合起来。然而,MLBS 到目前为止只针对同质种群,因此排除了个体间的所有变异来源。这一局限性是理论界关注的首要问题,因为任何将 MLBS 应用于真实数据的方法都需要考虑个体之间的变异。在本文中,我通过将种群划分为同质子种群,并将特定类群的生殖值作为个体进化适应性的加权因子,从而扩展了 MLBS 以考虑个体间的变异。由此产生的形式主义缩小了行为选择的理论基础与将理论应用于经验数据之间的差距,而经验数据自然包括个体间的差异。此外,扩展的 MLBS 还用于建立学习动态与个体适应性最大化之间的明确联系。这些研究成果拓展了 MLBS 作为定量分析学习和进化的一般理论框架的范围。
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引用次数: 0
Rethinking some roots of ecosystem approach in aquatic ecology: between the food cycle and lake metabolism 重新思考水生生态学中生态系统方法的某些根源:食物循环与湖泊新陈代谢之间的关系
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-04-26 DOI: 10.1007/s12064-024-00416-5
Alexandra L. Rizhinashvili

The present study provides new insight into the key aspects of the early formative period of the ecosystem concept in aquatic ecology. Raymond Lindeman’s trophodynamics is known to be a starting point for the development of the modern concept of ecosystem. The trophodynamic approach in ecology was proposed by Lindeman in his widely cited paper of 1942. Lindeman’s views are analyzed in comparison with the contemporary production studies in aquatic ecology. It is shown that a similar theoretical system has been proposed in the USSR at the end of the 1930s by Georgiy G. Vinberg. He introduced the concept of biotic balance based on the wide appraisal of the dark and light bottles method. The study shows that both Lindeman’s trophodynamics and Vinberg’s concept of biotic balance relied on an energy-based approach in considering the wholeness of a water body. The two scientists, however, differed in several important aspects concerning the interpretation of the role of living organisms. The holistic interpretation of ecosystem by Lindeman and Vinberg can be seen as part of the dilemma between physicalism and organicism. At the same time, the main emphasis in the concepts of both Vinberg and Lindemann was on the primary production component, a feature that was common to the first holistic systems in production hydrobiology (e.g., E. Naumann’s regional limnology). It is clear that modern problems of aquatic ecology should be addressed from the perspective of the organismocentric understanding of the ecosystem, but undoubtedly at the new level of development of this view.

本研究对水生生态学生态系统概念早期形成的关键方面提供了新的见解。众所周知,雷蒙德-林德曼的营养动力学是现代生态系统概念发展的起点。林德曼在 1942 年发表的论文中提出了生态学中的营养动力学方法,并被广泛引用。我们将林德曼的观点与当代水生生态学的生产研究进行了比较分析。研究表明,苏联在 20 世纪 30 年代末由 Georgiy G. Vinberg 提出了类似的理论体系。他在广泛评估暗瓶和光瓶法的基础上提出了生物平衡的概念。研究表明,林德曼的营养动力学和文伯格的生物平衡概念都是基于能量的方法来考虑水体的整体性。不过,两位科学家在解释生物体作用的几个重要方面存在差异。林德曼和文伯格对生态系统的整体解释可视为物理主义和有机主义之间两难选择的一部分。同时,文伯格和林德曼的概念主要强调初级生产部分,这也是生产水生物学中第一个整体系统(如 E. Naumann 的区域湖沼学)的共同特点。显然,现代水生生态学问题应从生态系统的生物中心认识的角度来解决,但无疑是在这一观点发展的新水平上解决。
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引用次数: 0
Mathematical analysis of a modified Volterra-Leslie chemostat Model 修正的 Volterra-Leslie 化合模型的数学分析
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-04-09 DOI: 10.1007/s12064-024-00415-6
Mohammed Amine Hamra

In this paper, we investigate the asymptotic behavior of a modified chemostat model. We first demonstrate the existence of equilibria. Then, we present a mathematical analysis for the model, the invariance, the positivity, the persistence of the solutions, and the asymptotic global stability of the interior equilibrium. Some numerical simulations are carried out to illustrate the main results.

在本文中,我们研究了修正的恒温模型的渐进行为。我们首先证明了均衡的存在。然后,我们对模型、解的不变性、实在性、持久性以及内部平衡的渐近全局稳定性进行了数学分析。为了说明主要结果,我们进行了一些数值模拟。
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引用次数: 0
Normalizing need not be the norm: count-based math for analyzing single-cell data. 规范化不一定是常态:用于分析单单元格数据的基于计数的数学。
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-02-01 Epub Date: 2023-11-10 DOI: 10.1007/s12064-023-00408-x
Samuel H Church, Jasmine L Mah, Günter Wagner, Casey W Dunn

Counting transcripts of mRNA are a key method of observation in modern biology. With advances in counting transcripts in single cells (single-cell RNA sequencing or scRNA-seq), these data are routinely used to identify cells by their transcriptional profile, and to identify genes with differential cellular expression. Because the total number of transcripts counted per cell can vary for technical reasons, the first step of many commonly used scRNA-seq workflows is to normalize by sequencing depth, transforming counts into proportional abundances. The primary objective of this step is to reshape the data such that cells with similar biological proportions of transcripts end up with similar transformed measurements. But there is growing concern that normalization and other transformations result in unintended distortions that hinder both analyses and the interpretation of results. This has led to an intense focus on optimizing methods for normalization and transformation of scRNA-seq data. Here, we take an alternative approach, by avoiding normalization and transformation altogether. We abandon the use of distances to compare cells, and instead use a restricted algebra, motivated by measurement theory and abstract algebra, that preserves the count nature of the data. We demonstrate that this restricted algebra is sufficient to draw meaningful and practical comparisons of gene expression through the use of the dot product and other elementary operations. This approach sidesteps many of the problems with common transformations, and has the added benefit of being simpler and more intuitive. We implement our approach in the package countland, available in python and R.

计数信使核糖核酸的转录物是现代生物学中观察的一种关键方法。随着单细胞转录物计数(单细胞RNA测序或scRNA-seq)的进展,这些数据通常用于通过转录谱鉴定细胞,并鉴定具有差异细胞表达的基因。由于技术原因,每个细胞计数的转录物总数可能会有所不同,许多常用的scRNA-seq工作流程的第一步是通过测序深度进行标准化,将计数转化为比例丰度。这一步骤的主要目的是重塑数据,使具有相似转录物生物学比例的细胞最终获得相似的转化测量值。但人们越来越担心,规范化和其他转变会导致意想不到的扭曲,阻碍分析和解释结果。这导致人们高度关注scRNA-seq数据的标准化和转换的优化方法。在这里,我们采取另一种方法,完全避免规范化和转换。我们放弃了使用距离来比较单元格,而是使用受测量理论和抽象代数驱动的受限代数,以保留数据的计数性质。我们证明了这个限制代数足以通过使用点积和其他初等运算对基因表达进行有意义和实用的比较。这种方法避开了常见转换的许多问题,并具有更简单、更直观的额外好处。我们在包countland中实现了我们的方法,该包在python和R中可用。
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引用次数: 0
Optimal dispersal and diffusion-enhanced robustness in two-patch metapopulations: origin's saddle-source nature matters. 双补丁元种群中的最佳扩散和扩散增强的稳健性:起源的鞍源性质很重要。
IF 1.1 4区 生物学 Q3 BIOLOGY Pub Date : 2024-02-01 Epub Date: 2024-02-21 DOI: 10.1007/s12064-023-00411-2
Marc Jorba-Cuscó, Ruth I Oliva-Zúniga, Josep Sardanyés, Daniel Pérez-Palau

A two-patch logistic metapopulation model is investigated both analytically and numerically focusing on the impact of dispersal on population dynamics. First, the dependence of the global dynamics on the stability type of the full extinction equilibrium point is tackled. Then, the behaviour of the total population with respect to the dispersal is studied analytically. Our findings demonstrate that diffusion plays a crucial role in the preservation of both subpopulations and the full metapopulation under the presence of stochastic perturbations. At low diffusion, the origin is a repulsor, causing the orbits to flow nearly parallel to the axes, risking stochastic extinctions. Higher diffusion turns the repeller into a saddle point. Orbits then quickly converge to the saddle's unstable manifold, reducing extinction chances. This change in the vector field enhances metapopulation robustness. On the other hand, the well-known fact that asymmetric conditions on the patches is beneficial for the total population is further investigated. This phenomenon has been studied in previous works for large enough or small enough values of the dispersal. In this work, we complete the theory for all values of the dispersal. In particular, we derive analytically a formula for the optimal value of the dispersal that maximizes the total population.

本研究通过分析和数值方法研究了一个双斑块逻辑元种群模型,重点研究了扩散对种群动态的影响。首先,研究了全局动态对完全灭绝平衡点稳定性类型的依赖性。然后,分析研究了扩散对总种群的影响。我们的研究结果表明,在存在随机扰动的情况下,扩散对亚种群和整个元种群的保存起着至关重要的作用。在低扩散条件下,原点是一个排斥因子,导致轨道几乎平行于轴线,面临随机灭绝的风险。较高的扩散会将排斥器变成一个鞍点。轨道会迅速向鞍的不稳定流形汇聚,从而降低灭绝的几率。矢量场的这种变化增强了元种群的稳健性。另一方面,我们进一步研究了众所周知的事实,即斑块上的不对称条件对整个种群有利。以往的研究已经针对足够大或足够小的分散值对这一现象进行了研究。在这项工作中,我们完成了所有分散值的理论研究。特别是,我们通过分析推导出了使总种群数量最大化的最佳分散值公式。
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引用次数: 0
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