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Strong Emergence in Biological Systems: Is It Open to Mathematical Reasoning? 生物系统中的强涌现:是否对数学推理开放?
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-08-31 DOI: 10.1007/s10441-021-09423-1
Zhifeng Hao, Jiayou Liu, Biao Wu, Min Yu, Lars H. Wegner

Complex, multigenic biological traits are shaped by the emergent interaction of proteins being the main functional units at the molecular scale. Based on a phenomenological approach, algorithms for quantifying two different aspects of emergence were introduced (Wegner and Hao in Progr Biophys Mol Biol 161:54–61, 2021) describing: (i) pairwise reciprocal interactions of proteins mutually modifying their contribution to a complex trait (denoted as weak emergence), and (ii) formation of a new, complex trait by a set of n ‘constitutive’ proteins at concentrations exceeding individual threshold values (strong emergence). The latter algorithm is modified here to take account of protein redundancy with respect to a complex trait (‘full redundancy’). Irreducibility is considered a necessary and sufficient criterion for strong biological emergence; if one constitutive protein is missing, or its concentration drops below the threshold the trait is lost. A definition based on ‘unpredictability’ is dismissed, because this criterion is irrelevant for the evolution of a complex trait, and apparent unpredictability may rather reflect our basic deficits in understanding unless we can provide an unequivocal proof for it. The phenomenological approach advocated here allows to identify hidden rules according to which strongly emergent traits may be organized. This is of high value for understanding the evolution of complex traits which seems to require the saltational advent of all constitutive proteins ‘in one turn’ to arrive at a functional trait providing for an improved fitness of the organism. Rather than being a purely random process, it may be guided by fundamental structural principles.

复杂的多基因生物学特征是由作为分子尺度上主要功能单元的蛋白质的突然相互作用形成的。基于现象学方法,引入了量化羽化的两个不同方面的算法(Wegner和Hao在Progr Biophys Mol Biol 161:54–612021中),描述了:(i)蛋白质的成对相互作用,相互改变它们对复杂性状的贡献(表示为弱羽化),由一组n“组成型”蛋白质组成的复杂性状,其浓度超过个体阈值(强烈涌现)。后一种算法在这里被修改,以考虑关于复杂特征的蛋白质冗余(“完全冗余”)。不可还原性被认为是强有力的生物出现的必要和充分的标准;如果一种组成蛋白缺失,或者其浓度下降到阈值以下,则该性状就会丧失。基于“不可预测性”的定义被驳回,因为这一标准与复杂特征的进化无关,而明显的不可预测可能反映了我们在理解方面的基本缺陷,除非我们能提供明确的证据。这里提倡的现象学方法允许识别隐藏的规则,根据这些规则可以组织强烈涌现的特征。这对于理解复杂性状的进化具有很高的价值,复杂性状似乎需要所有组成蛋白“一次”突变出现,才能形成一种功能性状,从而改善生物体的适应性。它不是一个纯粹的随机过程,而是受基本结构原理的指导。
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引用次数: 3
Optimal Control Strategies and Sensitivity Analysis of an HIV/AIDS-Resistant Model with Behavior Change 具有行为变化的HIV/ aids抵抗模型的最优控制策略及灵敏度分析
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-07-30 DOI: 10.1007/s10441-021-09421-3
Musa Rabiu, Robert Willie, Nabendra Parumasur

Despite several research on HIV/AIDS, it is still incumbent to investigate more effective control measures to mitigate its infection level. Therefore, we introduce an HIV/AIDS-resistant model with behavior change and study its basic properties. In order to determine the most sensitive parameters that are responsible for disease transmission with respect to the basic reproduction number and those responsible for disease prevalence with respect to the endemic equilibrium, the sensitivity analysis was established and it was confirmed that the influx rate of people into the infected population and total abstinence from all risk practices and endemic areas are some of the most sensitive parameters for disease spread and disease eradication, respectively. Furthermore, by considering controls (u_1) denoting the government’s intervention in promoting and encouraging behavior change, (u_2) representing intake of balanced nutritional supplementation, and (u_3) connoting antiretroviral therapy (ART), an optimal control problem was developed and analyzed. Before the establishment of the necessary conditions of the optimal control using Pontryagin’s Maximum Principle, we proved the existence of the optimal control triplet ((u_1(t),u_2(t),u_3(t)in Phi ,) where (Phi) is the control set at time t,) which has been neglected by many researchers in recent years. Using the Runge–Kutta scheme, the optimal control problem was solved to understand the best combination of control strategies. Using the demographic and epidemiological data for South Africa on HIV/AIDS, a numerical simulation was carried out and results are presented on 3D surface plots. The obtained results suggested that the combination of all the considered control measures is the best method to ensure disease eradication.

尽管对艾滋病毒/艾滋病进行了几项研究,但仍有责任调查更有效的控制措施,以降低其感染水平。因此,我们引入了一个具有行为变化的HIV/AIDS抗性模型,并研究了其基本性质。为了确定关于基本繁殖数的负责疾病传播的最敏感参数和关于地方病均衡的负责疾病流行的参数,建立了敏感性分析,并证实感染人群的流入率和完全戒除所有风险做法和流行地区分别是疾病传播和根除的一些最敏感的参数。此外,通过考虑代表政府干预促进和鼓励行为改变的对照组(u1)、代表均衡营养补充的摄入的对照组和代表抗逆转录病毒疗法的对照组,提出并分析了一个最优控制问题。在利用Pontryagin最大值原理建立最优控制的必要条件之前,我们证明了最优控制三元组((u1(t),u2(t。使用Runge–Kutta方案,解决了最优控制问题,以了解控制策略的最佳组合。利用南非关于艾滋病毒/艾滋病的人口统计和流行病学数据,进行了数值模拟,结果显示在三维曲面图上。所获得的结果表明,将所有考虑的控制措施相结合是确保根除疾病的最佳方法。
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引用次数: 6
Organic Codes: A Unifying Concept for Life 有机密码:生命的统一概念
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-07-30 DOI: 10.1007/s10441-021-09422-2
Savio Torres de Farias, Francisco Prosdocimi, Gustavo Caponi

Although the knowledge about biological systems has advanced exponentially in recent decades, it is surprising to realize that the very definition of Life keeps presenting theoretical challenges. Even if several lines of reasoning seek to identify the essence of life phenomenon, most of these thoughts contain fundamental problem in their basic conceptual structure. Most concepts fail to identify either necessary or sufficient features to define life. Here, we analyzed the main conceptual frameworks regarding theoretical aspects that have been supporting the most accepted concepts of life, such as (i) the physical, (ii) the cellular and (iii) the molecular approaches. Based on an ontological analysis, we propose that Life should not be positioned under the ontological category of Matter. Yet, life should be better understood under the top-level ontology of “Process”. Exercising an epistemological approach, we propose that the essential characteristic that pervades each and every living being is the presence of organic codes. Therefore, we explore theories in biosemiotics and code biology in order to propose a clear concept of life as a macrocode composed by multiple inter-related coding layers. This way, as life is a sort of metaphysical process of encoding, the living beings became the molecular materialization of that process. From the proposed concept, we show that the evolutionary process is a fundamental characteristic for life’s maintenance but it is not necessary to define life, as many organisms are clearly alive but they do not participate in the evolutionary process (such as infertile hybrids). The current proposition opens a fertile field of debate in astrobiology, epistemology, biosemiotics, code biology and robotics.

尽管近几十年来,有关生物系统的知识呈指数级增长,但令人惊讶的是,生命的定义本身就不断提出理论挑战。即使有几条推理路线试图识别生命现象的本质,但这些思想大多在其基本概念结构中包含着根本问题。大多数概念都无法确定定义生命的必要或充分特征。在这里,我们分析了关于理论方面的主要概念框架,这些理论方面一直支持最被接受的生命概念,如(i)物理方法、(ii)细胞方法和(iii)分子方法。在本体论分析的基础上,我们提出生命不应被置于物质的本体论范畴之下。然而,生活应该在“过程”的顶层本体论下得到更好的理解。运用认识论方法,我们提出,每个生命体的本质特征都是有机代码的存在。因此,我们探索了生物计量学和编码生物学的理论,以便提出一个明确的概念,即生命是由多个相互关联的编码层组成的宏代码。这样,由于生命是一种形而上学的编码过程,生命就成为了这个过程的分子物化。根据提出的概念,我们表明进化过程是维持生命的基本特征,但没有必要定义生命,因为许多生物体显然是活着的,但它们不参与进化过程(例如不育的杂交种)。目前的命题为天体生物学、认识论、生物计量学、代码生物学和机器人学开辟了一个肥沃的辩论领域。
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引用次数: 1
Factors in Protobiomonomer Selection for the Origin of the Standard Genetic Code 标准遗传密码起源的原生物单体选择因素
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-07-20 DOI: 10.1007/s10441-021-09420-4
Alexander I. Saralov

Natural selection of specific protobiomonomers during abiogenic development of the prototype genetic code is hindered by the diversity of structural, spatial, and rotational isomers that have identical elemental composition and molecular mass (M), but can vary significantly in their physicochemical characteristics, such as the melting temperature Tm, the Tm:M ratio, and the solubility in water, due to different positions of atoms in the molecule. These parameters differ between cis- and trans-isomers of dicarboxylic acids, spatial monosaccharide isomers, and structural isomers of α-, β-, and γ-amino acids. The stable planar heterocyclic molecules of the major nucleobases comprise four (C, H, N, O) or three (C, H, N) elements and contain a single –C=C bond and two nitrogen atoms in each heterocycle involved in C–N and C=N bonds. They exist as isomeric resonance hybrids of single and double bonds and as a mixture of tautomer forms due to the presence of –C=O and/or –NH2 side groups. They are thermostable, insoluble in water, and exhibit solid-state stability, which is of central importance for DNA molecules as carriers of genetic information. In M–Tm diagrams, proteinogenic amino acids and the corresponding codons are distributed fairly regularly relative to the distinct clusters of purine and pyrimidine bases, reflecting the correspondence between codons and amino acids that was established in different periods of genetic code development. The body of data on the evolution of the genetic code system indicates that the elemental composition and molecular structure of protobiomonomers, and their M, Tm, photostability, and aqueous solubility determined their selection in the emergence of the standard genetic code.

在原型遗传密码的非生物发育过程中,特定原型生物单体的自然选择受到结构、空间和旋转异构体多样性的阻碍,这些异构体具有相同的元素组成和分子量(M),但其物理化学特性可能显著变化,如熔融温度Tm、Tm:M比和在水中的溶解度,由于原子在分子中的不同位置。这些参数在二羧酸的顺式和反式异构体、空间单糖异构体以及α-、β-和γ-氨基酸的结构异构体之间不同。主要核碱基的稳定平面杂环分子包括四个(C,H,N,O)或三个(C、H,N)元素,并在每个杂环中包含一个–C=C键和两个氮原子,涉及C–N和C=N键。由于–C=O和/或–NH2侧基的存在,它们以单键和双键的异构共振杂化物以及互变异构体形式的混合物存在。它们是热稳定的,不溶于水,并表现出固态稳定性,这对于作为遗传信息载体的DNA分子来说至关重要。在M–Tm图中,蛋白质生成氨基酸和相应的密码子相对于嘌呤和嘧啶碱基的不同簇分布相当规则,反映了密码子和氨基酸之间的对应关系,这些对应关系是在遗传密码发展的不同时期建立的。遗传密码系统进化的大量数据表明,原生物单体的元素组成和分子结构,以及它们的M、Tm、光稳定性和水溶性,决定了它们在标准遗传密码出现时的选择。
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引用次数: 0
What is Causal Specificity About, and What is it Good for in Philosophy of Biology? 因果专一性是什么,对生物学哲学有什么好处?
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-07-12 DOI: 10.1007/s10441-021-09419-x
María Ferreira Ruiz

The concept of causal specificity is drawing considerable attention from philosophers of biology. It became the rationale for rejecting (and occasionally, accepting) a thesis of causal parity of developmental factors. This literature assumes that attributing specificity to causal relations is at least in principle a straightforward (if not systematic) task. However, the parity debate in philosophy of biology seems to be stuck at a point where it is not the biological details that will help move forward. In this paper, I take a step back to reexamine the very idea of causal specificity and its intended role in the parity dispute in philosophy of biology. I contend that the idea of causal specificity across variations as currently discussed in the literature is irreducibly twofold in nature: it is about two independent components that are not mutually entailed. I show this to be the source of prior complications with the notion of specificity itself that ultimately affect the purposes for which it is often invoked, notably to settle the parity dispute.

因果特异性的概念引起了生物学哲学家的极大关注。它成为了拒绝(偶尔也会接受)发展因素因果对等论点的理由。这篇文献假设,将特异性归因于因果关系至少在原则上是一项直接的(如果不是系统的)任务。然而,生物学哲学中的平等争论似乎停留在一个点上,即生物学细节并不能帮助向前发展。在这篇论文中,我退一步重新审视因果特异性的概念及其在生物学哲学中的宇称争议中的预期作用。我认为,目前文献中讨论的跨变异的因果特异性的概念在本质上是不可还原的双重:它是关于两个不相互包含的独立组成部分。我表明,这是特定性概念本身先前复杂化的根源,最终影响到它经常被援引的目的,特别是为了解决平等争端。
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引用次数: 0
A Human-Bovine Schistosomiasis Mathematical Model with Treatment and Mollusciciding 人牛血吸虫病的数学模型与治疗和杀螺
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-06-30 DOI: 10.1007/s10441-021-09416-0
Solomon Kadaleka, Shirley Abelman, Jean M. Tchuenche

To mitigate the spread of schistosomiasis, a deterministic human-bovine mathematical model of its transmission dynamics accounting for contaminated water reservoirs, including treatment of bovines and humans and mollusciciding is formulated and theoretically analyzed. The disease-free equilibrium is locally and globally asymptotically stable whenever the basic reproduction number (R_0<1), while global stability of the endemic equilibrium is investigated by constructing a suitable Lyapunov function. To support the analytical results, parameter values from published literature are used for numerical simulations and where applicable, uncertainty analysis on the non-dimensional system parameters is performed using the Latin Hypercube Sampling and Partial Rank Correlation Coefficient techniques. Sensitivity analysis to determine the relative importance of model parameters to disease transmission shows that the environment-related parameters namely, (varepsilon _s) (snails shedding rate of cercariae), (p_s) (probability that cercariae shed by snails survive), c (fraction of the contaminated environment sprayed by molluscicides) and (mu _c) (mortality rate of cercariae) are the most significant to mitigate the spread of schistosomiasis. Mollusciciding, which directly impacts the contaminated environment as a single control strategy is more effective compared to treatment. However, concurrently applying mollusciciding and treatment will yield a better outcome.

为了减缓血吸虫病的传播,建立了一个确定的人-牛传播动力学数学模型,该模型考虑了受污染的水库,包括牛和人的处理以及灭螺。当基本繁殖数为(R_0<;1)时,无病平衡是局部和全局渐近稳定的,而通过构造合适的李雅普诺夫函数来研究地方病平衡的全局稳定性。为了支持分析结果,已发表文献中的参数值用于数值模拟,在适用的情况下,使用拉丁超立方体采样和偏秩相关系数技术对无量纲系统参数进行不确定性分析。确定模型参数对疾病传播的相对重要性的敏感性分析表明,与环境相关的参数,即(varepsilon _s)(尾蚴的蜗牛脱落率)、(p_s)(蜗牛脱落的尾蚴存活的概率),c(被杀螺剂喷洒的污染环境的一部分)和(mu_c)(尾蚴死亡率)对减缓血吸虫病的传播最为重要。与处理相比,作为单一控制策略直接影响污染环境的软体动物冷冻更有效。然而,同时应用灭螺和治疗将产生更好的结果。
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引用次数: 0
How Do Trees Grow in Girth? Controversy on the Role of Cellular Events in the Vascular Cambium 树木的周长是如何增长的?关于维管形成层中细胞事件作用的争论
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-06-21 DOI: 10.1007/s10441-021-09418-y
Anna Wilczek-Ponce, Wiesław Włoch, Muhammad Iqbal

Radial growth has long been a subject of interest in tree biology research. Recent studies have brought a significant change in the understanding of some basic processes characteristic to the vascular cambium, a meristem that produces secondary vascular tissues (phloem and xylem) in woody plants. A new hypothesis regarding the mechanism of intrusive growth of the cambial initials, which has been ratified by studies of the arrangement of cambial cells, negates the influence of this apical cell growth on the expansion of the cambial circumference. Instead, it suggests that the tip of the elongating cambial initial intrudes between the tangential (periclinal) walls, rather than the radial (anticlinal) walls, of the initial(s) and its(their) derivative(s) lying ahead of the elongating cell tip. The new concept also explains the hitherto obscure mechanism of the cell event called ‘elimination of initials’. This article evaluates these new concepts of the cambial cell dynamics and offers a new interpretation for some curious events occurring in the cambial meristem in relation to the radial growth in woody plants.

径向生长一直是树木生物学研究中的一个感兴趣的主题。最近的研究使人们对维管形成层(一种在木本植物中产生次生维管组织(韧皮部和木质部)的分生组织)的一些基本过程的理解发生了重大变化。一个关于形成层首字母侵入性生长机制的新假说,已被形成层细胞排列的研究所证实,否定了这种顶端细胞生长对形成层周长扩张的影响。相反,它表明伸长形成层初始的尖端侵入位于伸长细胞尖端之前的初始及其衍生物的切向(周向壁)壁之间,而不是径向(背斜)壁之间。这一新概念还解释了迄今为止被称为“首字母消除”的细胞事件的模糊机制。本文评价了形成层细胞动力学的这些新概念,并对与木本植物径向生长有关的形成层分生组织中发生的一些奇怪事件提供了新的解释。
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引用次数: 6
The Effect of Mitochondrial DNA Half-Life on Deletion Mutation Proliferation in Long Lived Cells 线粒体DNA半衰期对长寿细胞中缺失突变增殖的影响
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-06-15 DOI: 10.1007/s10441-021-09417-z
Alan G. Holt, Adrian M. Davies

The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions ((text {mtDNA}_{del})) have a replicative advantage over wild-type ((text {mtDNA}_{wild})) and that this is detrimental to the host cell, especially in post-mitotic cells. An individual cell can be viewed as forming a closed ecosystem containing a large population of independently replicating mtDNA. Within this enclosed environment a selfishly replicating (text {mtDNA}_{del}) would compete with the (text {mtDNA}_{wild}) for space and resources to the detriment of the host cell. In this paper, we use a computer simulation to model cell survival in an environment where (text {mtDNA}_{wild}) compete with (text {mtDNA}_{del}) such that the cell expires upon (text {mtDNA}_{wild}) extinction. We focus on the survival time for long lived post-mitotic cells, such as neurons. We confirm previous observations that (text {mtDNA}_{del}) do have a replicative advantage over (text {mtDNA}_{wild}). As expected, cell survival times diminished with increased mutation probabilities, however, the relationship between survival time and mutation rate was non-linear, that is, a ten-fold increase in mutation probability only halved the survival time. The results of our model also showed that a modest increase in half-life had a profound affect on extending cell survival time, thereby, mitigating the replicative advantage of (text {mtDNA}_{del}). Given the relevance of mitochondrial dysfunction to various neurodegenerative conditions, we propose that therapies to increase mtDNA half-life could significantly delay their onset.

具有缺失突变的线粒体DNA(mtDNA)的增殖与衰老和年龄相关的神经退行性疾病有关。在本研究中,我们模拟了mtDNA半衰期对mtDNA竞争和选择的影响。有人提出突变缺失((text{mtDNA}_{del})相比野生型((text{mtDNA}_{wild})),并且这对宿主细胞是有害的,尤其是在有丝分裂后的细胞中。单个细胞可以被视为形成一个封闭的生态系统,其中包含大量独立复制的mtDNA。在这个封闭的环境中,自私地复制{mtDNA}_{del})将与(text{mtDNA}_{wild})以获取空间和资源,从而损害宿主细胞。在本文中,我们使用计算机模拟来模拟细胞在如下环境中的存活:{mtDNA}_{wild})与(text)竞争{mtDNA}_{del}),使得单元格在(text{mtDNA}_{野生})灭绝。我们关注长寿的有丝分裂后细胞的生存时间,例如神经元。我们确认之前的观察结果,(text{mtDNA}_{del})确实比(text)具有复制优势{mtDNA}_{wild})。正如预期的那样,细胞存活时间随着突变概率的增加而减少,然而,存活时间和突变率之间的关系是非线性的,即突变概率增加十倍只会使存活时间减半。我们模型的结果还表明,半衰期的适度增加对延长细胞存活时间有着深远的影响,从而减轻了(text)的复制优势{mtDNA}_{del})。鉴于线粒体功能障碍与各种神经退行性疾病的相关性,我们提出增加线粒体DNA半衰期的疗法可以显著延缓其发病。
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引用次数: 6
Correction to: Biology and Pragmatism: The Organism-Environment Bond 更正:生物学与实用主义:生物与环境的结合
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-06-01 DOI: 10.1007/s10441-021-09414-2
David Depew
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引用次数: 0
Memory in Ion Channel Kinetics 离子通道动力学中的记忆
IF 1.3 4区 生物学 Q4 MATHEMATICAL & COMPUTATIONAL BIOLOGY Pub Date : 2021-05-27 DOI: 10.1007/s10441-021-09415-1
M. P. Silva, C. G. Rodrigues, W. A. Varanda, R. A. Nogueira

Ion channels are transport proteins present in the lipid bilayers of biological membranes. They are involved in many physiological processes, such as the generation of nerve impulses, hormonal secretion, and heartbeat. Conformational changes in the ion channel-forming protein allow the opening or closing of pores to control the ionic flux through the cell membranes. The opening and closing of the ion channel have been classically treated as a random kinetic process, known as a Markov process. Here the time the channel remains in a given state is assumed to be independent of the condition it had in the previous state. More recently, however, several studies have shown that this process is not random but a deterministic one, where both the open and closed dwell-times and the ionic current flowing through the channel are history-dependent. This property is called long memory or long-range correlation. However, there is still much controversy regarding how this memory originates, which region of the channel is responsible for this property, and which models could best reproduce the memory effect. In this article, we provide a review of what is, where it is, its possible origin, and the mathematical methods used to analyze the long-term memory present in the kinetic process of ion channels.

离子通道是存在于生物膜的脂质双层中的转运蛋白。它们参与许多生理过程,如神经冲动的产生、激素分泌和心跳。离子通道形成蛋白的构象变化允许孔隙的打开或关闭,以控制通过细胞膜的离子通量。离子通道的打开和关闭通常被视为一个随机动力学过程,称为马尔可夫过程。这里,信道保持在给定状态的时间被假设为独立于它在先前状态中的条件。然而,最近的几项研究表明,这一过程不是随机的,而是确定性的,其中打开和关闭的停留时间以及流经通道的离子电流都与历史有关。这种特性称为长内存或长程相关性。然而,关于这种记忆是如何产生的,通道的哪个区域负责这种特性,以及哪些模型可以最好地再现记忆效应,仍然存在很多争议。在这篇文章中,我们回顾了什么是,在哪里,它的可能起源,以及用于分析离子通道动力学过程中存在的长期记忆的数学方法。
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引用次数: 7
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