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Contrasting philosophical and scientific views in the long history of studying the generation of form in development 在研究发展过程中形式产生的漫长历史中,哲学和科学观点的对立。
IF 2 4区 生物学 Q2 BIOLOGY Pub Date : 2024-06-24 DOI: 10.1016/j.biosystems.2024.105260
Ute Deichmann

Focusing on the opposing ways of thinking of philosophers and scientists to explain the generation of form in biological development, I show that today's controversies over explanations of early development bear fundamental similarities to the dichotomy of preformation theory versus epigenesis in Greek antiquity. They are related to the acceptance or rejection of the idea of a physical form of what today would be called information for the generating of the embryo as a necessary pre-requisite for specific development and heredity.

As a recent example, I scrutinize the dichotomy of genomic causality versus self-organization in 20th and 21st century theories of the generation of form. On the one hand, the generation of patterns and form, as well as the constant outcome in development, are proposed to be causally related to something that is "preformed" in the germ cells, the nucleus of germ cells, or the genome. On the other hand, it is proposed that there is no pre-existing form or information, and development is seen as a process where genuinely new characters emerge from formless matter, either by immaterial "forces of life," or by physical-chemical processes of self-organization.

I also argue that these different ways of thinking and the research practices associated with them are not equivalent, and maintain that it is impossible to explain the generation of form and constant outcome of development without the assumption of the transmission of pre-existing information in the form of DNA sequences in the genome. Only in this framework of "preformed" information can "epigenesis" in the form of physical and chemical processes of self-organization play an important role.

我着重探讨了哲学家和科学家在解释生物发育过程中形式的产生时所采用的截然相反的思维方式,并指出,当今关于早期发育解释的争论与古希腊时期形成前理论和表观遗传学的对立有着根本的相似之处。它们都与接受或拒绝这样一种观点有关,即今天被称为胚胎生成信息的物理形式是特定发育和遗传的必要前提。作为最近的一个例子,我仔细研究了 20 世纪和 21 世纪形式生成理论中基因组因果关系与自组织的二分法。一方面,模式和形式的产生以及发育过程中的恒定结果被认为与生殖细胞、生殖细胞核或基因组中 "预先形成 "的东西有因果关系。另一方面,有人认为不存在预先存在的形式或信息,发育被视为从无形物质中产生真正新特征的过程,或者是通过非物质的 "生命力量",或者是通过物理化学的自组织过程。我还认为,这些不同的思维方式以及与之相关的研究实践并不等同,并坚持认为,如果不假定基因组中以 DNA 序列形式存在的先在信息的传递,就不可能解释形式的产生和发展的恒定结果。只有在这种 "预先形成的 "信息框架内,以物理和化学自组织过程为形式的 "表观成因 "才能发挥重要作用。
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引用次数: 0
Size matters in metabolic scaling: Critical role of the thermodynamic efficiency of ATP synthesis and its dependence on mitochondrial H+ leak across mammalian species 新陈代谢规模的大小很重要:ATP 合成的热力学效率的关键作用及其对不同哺乳动物线粒体 H+ 泄漏的依赖性
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-06-19 DOI: 10.1016/j.biosystems.2024.105255
Sunil Nath

In this last article of the trilogy, the unified biothermokinetic theory of ATP synthesis developed in the previous two papers is applied to a major problem in comparative physiology, biochemistry, and ecology—that of metabolic scaling as a function of body mass across species. A clear distinction is made between intraspecific and interspecific relationships in energy metabolism, clearing up confusion that had existed from the very beginning since Kleiber first proposed his mouse-to-elephant rule almost a century ago. It is shown that the overall mass exponent of basal/standard metabolic rate in the allometric relationship P=P0Mb+b is composed of two parts, one emerging from the relative intraspecific constancy of the slope (b), and the other (b) arising from the interspecific variation of the mass coefficient, a(M) with body size. Quantitative analysis is shown to reveal the hidden underlying relationship followed by the interspecific mass coefficient, a(M)=P0M0.10, and a universal value of P0=3.23 watts, W is derived from empirical data on mammals from mouse to cattle. The above relationship is shown to be understood only within an evolutionary biological context, and provides a physiological explanation for Cope's rule. The analysis also helps in fundamentally understanding how variability and a diversity of scaling exponents arises in allometric relations in biology and ecology. Next, a molecular-level understanding of the scaling of metabolism across mammalian species is shown to be obtained by consideration of the thermodynamic efficiency of ATP synthesis η, taking mitochondrial proton leak as a major determinant of basal metabolic rate in biosystems. An iterative solution is obtained by solving the mathematical equations of the biothermokinetic ATP theory, and the key thermodynamic parameters, e.g. the degree of coupling q, the operative P/O ratio, and the metabolic efficiency of ATP synthesis η are quantitatively evaluated for mammals from rat to cattle. Increases in η (by 15%) over a 2000

在这三部曲的最后一篇文章中,前两篇论文中提出的统一的 ATP 合成生物热动力学理论被应用于比较生理学、生物化学和生态学中的一个主要问题--即作为体重函数的跨物种新陈代谢比例。论文明确区分了能量代谢中的种内关系和种间关系,澄清了自近一个世纪前克莱伯首次提出小鼠对大象规则以来一直存在的混淆。研究表明,在异速关系 P=P0Mb′+b 中,基础/标准代谢率的总体质量指数由两部分组成,一部分来自斜率(b)在种内的相对恒定性,另一部分(b′)来自质量系数 a(M)随体型的种间变化。定量分析显示,种间质量系数 a(M)=P0M0.10 和 P0=3.23 瓦特的普遍值 W 是由从小鼠到牛的哺乳动物的经验数据得出的。上述关系只有在生物进化的背景下才能被理解,并为科普规则提供了生理学解释。该分析还有助于从根本上理解生物学和生态学中的异速关系是如何产生变异性和比例指数多样性的。接下来,通过考虑 ATP 合成的热力学效率 η,并将线粒体质子泄漏作为生物系统中基础代谢率的主要决定因素,可以从分子层面理解哺乳动物物种间新陈代谢的比例关系。通过求解生物热动力学 ATP 理论的数学方程,得到了一个迭代解,并定量评估了从大鼠到牛等哺乳动物的关键热力学参数,如耦合度 q、工作 P/O 比率和 ATP 合成代谢效率 η。从大鼠到牛,在 2000 倍的体型范围内,η 的增加(增加 ∼15%)主要源于线粒体 H+ 泄漏率降低了 ∼3 倍,统一 ATP 理论对此进行了量化。详细讨论了解释基础代谢的生物化学和机理后果,以及由此产生的各种分子影响。这些结果被扩展到最大代谢率,并作为一般 ATP 理论的极限情况进行数学解释。指出了分析的局限性。总之,基于 ATP 合成的统一生物热动力学理论的全面定量分析,解决了生物学、生理学和生态学中关于能量代谢与体型比例的核心问题。
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引用次数: 0
Biological thermodynamics: Bridging the gap between physics and life 生物热力学:弥合物理学与生命之间的鸿沟。
IF 2 4区 生物学 Q2 BIOLOGY Pub Date : 2024-06-14 DOI: 10.1016/j.biosystems.2024.105258
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引用次数: 0
Use of directed quasi-metric distances for quantifying the information of gene families 利用定向准计量距离量化基因家族的信息。
IF 2 4区 生物学 Q2 BIOLOGY Pub Date : 2024-06-12 DOI: 10.1016/j.biosystems.2024.105256

A large hindrance to analyzing information in genetic or protein sequence data has been a lack of a mathematical framework for doing so. In this paper, we present a multinomial probability space X as a general foundation for multicategory discrete data, where categories refer to variants/alleles of biosequences. The external information that is infused in order to generate a sample of such data is quantified as a distance on X between the prior distribution of data and the empirical distribution of the sample. A number of distances on X are treated. All of them have an information theoretic interpretation, reflecting the information that the sampling mechanism provides about which variants that have a selective advantage and therefore appear more frequently compared to prior expectations. This includes distances on X based on mutual information, conditional mutual information, active information, and functional information. The functional information distance is singled out as particularly useful. It is simple and has intuitive interpretations in terms of 1) a rejection sampling mechanism, where functional entities are retained, whereas non-functional categories are censored, and 2) evolutionary waiting times. The functional information is also a quasi-metric on X, with information being measured in an asymmetric, mountainous landscape. This quasi-metric property is also retained for a robustified version of the functional information distance that allows for mutations in the sampling mechanism. The functional information quasi-metric has been applied with success on bioinformatics data sets, for proteins and sequence alignment of protein families.

分析基因或蛋白质序列数据信息的一大障碍是缺乏相关的数学框架。在本文中,我们提出了一个多二项概率空间,作为多类别离散数据的一般基础,其中类别指的是生物序列的变体/等位基因。为生成此类数据样本而注入的外部信息被量化为数据的先验分布与样本的经验分布之间的距离。我们处理了一系列的 "上 "距离。它们都有一个信息论的解释,反映了抽样机制提供的信息,即哪些变体具有选择优势,因此与先前的预期相比出现的频率更高。这包括基于互信息、条件互信息、主动信息和功能信息的距离。功能信息距离尤其有用。它很简单,而且可以从以下两个方面进行直观的解释:1)剔除抽样机制,即保留功能性实体,而剔除非功能性类别;2)进化等待时间。功能信息也是一种准度量,信息是在不对称的多山景观中测量的。功能信息距离的稳健化版本也保留了这一准度量属性,该版本允许采样机制发生突变。功能信息准计量已成功应用于生物信息学数据集、蛋白质和蛋白质族的序列比对。
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引用次数: 0
What do stimulated beta cells have in common with cancer cells? 受刺激的 Beta 细胞与癌细胞有什么共同之处?
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-06-12 DOI: 10.1016/j.biosystems.2024.105257
Marko Marhl

This study investigates the metabolic parallels between stimulated pancreatic beta cells and cancer cells, focusing on glucose and glutamine metabolism. Addressing the significant public health challenges of Type 2 Diabetes (T2D) and cancer, we aim to deepen our understanding of the mechanisms driving insulin secretion and cellular proliferation. Our analysis of anaplerotic cycles and the role of NADPH in biosynthesis elucidates their vital functions in both processes. Additionally, we point out that both cell types share an antioxidative response mediated by the Nrf2 signaling pathway, glutathione synthesis, and UCP2 upregulation. Notably, UCP2 facilitates the transfer of C4 metabolites, enhancing reductive TCA cycle metabolism. Furthermore, we observe that hypoxic responses are transient in beta cells post-stimulation but persistent in cancer cells. By synthesizing these insights, the research may suggest novel therapeutic targets for T2D, highlighting the shared metabolic strategies of stimulated beta cells and cancer cells. This comparative analysis not only illuminates the metabolic complexity of these conditions but also emphasizes the crucial role of metabolic pathways in cell function and survival, offering fresh perspectives for tackling T2D and cancer challenges.

这项研究调查了受刺激的胰腺β细胞和癌细胞之间的代谢相似性,重点是葡萄糖和谷氨酰胺代谢。为了应对 2 型糖尿病(T2D)和癌症这一重大公共卫生挑战,我们旨在加深对胰岛素分泌和细胞增殖驱动机制的理解。我们对无凋亡周期和 NADPH 在生物合成中的作用进行了分析,阐明了它们在这两个过程中的重要功能。此外,我们还指出,两种细胞类型都具有由 Nrf2 信号通路、谷胱甘肽合成和 UCP2 上调介导的抗氧化反应。值得注意的是,UCP2 促进了 C4 代谢物的转移,增强了还原性 TCA 循环代谢。此外,我们还观察到,缺氧反应在刺激后的β细胞中是短暂的,但在癌细胞中却是持续的。通过综合这些见解,这项研究可为治疗 T2D 提出新的治疗目标,同时强调受刺激的 beta 细胞和癌细胞的共同代谢策略。这种比较分析不仅揭示了这些情况下代谢的复杂性,还强调了代谢途径在细胞功能和存活中的关键作用,为应对 T2D 和癌症挑战提供了新的视角。
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引用次数: 0
Determining cellular lineage directed networks in hematopoiesis using single-cell transcriptomic data and volatility-constrained correlation 利用单细胞转录组数据和波动约束相关性确定造血过程中的细胞系定向网络
IF 2 4区 生物学 Q2 BIOLOGY Pub Date : 2024-06-11 DOI: 10.1016/j.biosystems.2024.105248
Tomoshiro Ochiai , Jose C. Nacher

Single-cell transcriptome sequencing (scRNA-seq) has revolutionized our understanding of cellular processes by enabling the analysis of expression profiles at an individual cell level. This technology has shown promise in uncovering new cell types, gene functions, cell differentiation, and trajectory inference through the study of various biological processes, such as hematopoiesis. Recent scRNA-seq analysis of mouse bone marrow cells has provided a network model of hematopoietic lineage. However, all data analyses have predicted undirected network maps for the associated cell trajectories. Moreover, the debate regarding the origin of basophil cells still persists. In this work, we apply the Volatility Constrained (VC) correlation method to predict not only the network structure but also the causality or directionality between the cell types present in the hematopoietic process. Our findings suggest a dual origin of basophils, from both granulocyte/macrophage and erythrocyte progenitors, the latter being a trajectory less explored in previous research. The proposed approach and predictions may assist in developing a complete hematopoietic process map, impacting our understanding of hematopoiesis and providing a robust directional network framework for further biomedical research.

单细胞转录组测序(scRNA-seq)通过分析单个细胞水平的表达谱,彻底改变了我们对细胞过程的理解。通过对造血等各种生物过程的研究,这项技术有望发现新的细胞类型、基因功能、细胞分化和轨迹推断。最近对小鼠骨髓细胞的 scRNA-seq 分析提供了一个造血系网络模型。然而,所有数据分析都预测了相关细胞轨迹的不定向网络图。此外,关于嗜碱性粒细胞起源的争论依然存在。在这项工作中,我们应用波动约束(VC)相关方法不仅预测了网络结构,还预测了造血过程中细胞类型之间的因果关系或方向性。我们的研究结果表明,嗜碱性粒细胞具有双重起源,既来自粒细胞/巨噬细胞,也来自红细胞祖细胞,而后者是以往研究中较少探讨的一种轨迹。所提出的方法和预测可能有助于绘制完整的造血过程图,影响我们对造血的理解,并为进一步的生物医学研究提供一个强大的定向网络框架。
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引用次数: 0
Thermodynamic model for memory 记忆的热力学模型
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-06-10 DOI: 10.1016/j.biosystems.2024.105247
Qinyi Zhao

A thermodynamic model for memory formation is proposed. Key points include: 1) Any thought or consciousness corresponds to a thermodynamic system of nerve cells. 2) The system concept of nerve cells can only be described by thermodynamics of condensed matter. 3) The memory structure is logically associated with the system structure or the normal structure of biology. 4) The development of our thoughts is processed irreversibly, and numerous states or thoughts can be generated. 5) Memory formation results from the reorganization and change of cellular structures (or memory structures), which are related to nerve cell skeleton and membrane. Their alteration can change the excitability of nerve cells and the pathway of neural impulse conduction. 6) Amnesia results from the loss of thermodynamic stability of the memory structure, which can be achieved by different ways. Some related phenomena and facts are discussed. The analysis shows that thermodynamics can account for the basic properties of memory.

提出了记忆形成的热力学模型。要点包括1) 任何思想或意识都与神经细胞的热力学系统相对应。2) 神经细胞的系统概念只能用凝聚态物质的热力学来描述。3) 记忆结构在逻辑上与生物的系统结构或正常结构相关联。4) 我们思想的发展过程是不可逆的,可以产生无数的状态或思想。5) 记忆的形成源于细胞结构(或记忆结构)的重组和变化,而细胞结构与神经细胞的骨架和膜有关。它们的改变可以改变神经细胞的兴奋性和神经冲动的传导途径。6) 失忆的原因是记忆结构失去了热力学稳定性,这可以通过不同的方式实现。讨论了一些相关的现象和事实。分析表明,热力学可以解释记忆的基本特性。
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引用次数: 0
Effective identification and differential analysis of anticancer peptides 有效识别和差异分析抗癌肽。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-06-05 DOI: 10.1016/j.biosystems.2024.105246
Lichao Zhang , Xueli Hu , Kang Xiao , Liang Kong

Anticancer peptides (ACPs) have recently emerged as promising cancer therapeutics due to their selectivity and lower toxicity. However, the number of experimentally validated ACPs is limited, and identifying ACPs from large-scale sequence data is time-consuming and expensive. Therefore, it is critical to develop and improve upon existing computational models for identifying ACPs. In this study, a computational method named ACP_DA was proposed based on peptide residue composition and physiochemical properties information. To curtail overfitting and reduce computational costs, a sequential forward selection method was utilized to construct the optimal feature groups. Subsequently, the feature vectors were fed into light gradient boosting machine classifier for model construction. It was observed by an independent set test that ACP_DA achieved the highest Matthew's correlation coefficient of 0.63 and accuracy of 0.8129, displaying at least a 2% enhancement compared to state-of-the-art methods. The satisfactory results demonstrate the effectiveness of ACP_DA as a powerful tool for identifying ACPs, with the potential to significantly contribute to the development and optimization of promising therapies. The data and resource codes are available at https://github.com/Zlclab/ACP_DA.

抗癌肽(ACPs)具有选择性和低毒性,最近已成为很有前途的癌症疗法。然而,经过实验验证的抗癌肽数量有限,而且从大规模序列数据中识别抗癌肽既耗时又昂贵。因此,开发和改进现有的 ACPs 识别计算模型至关重要。本研究基于肽残基组成和理化性质信息,提出了一种名为 ACP_DA 的计算方法。为了抑制过拟合并降低计算成本,该方法采用了一种顺序前向选择法来构建最佳特征组。随后,将特征向量输入到轻梯度提升机分类器中构建模型。通过独立集测试发现,ACP_DA 的马修相关系数最高,达到 0.63,准确率为 0.8129,与最先进的方法相比至少提高了 2%。这些令人满意的结果表明,ACP_DA 是一种识别 ACP 的强大工具,具有显著促进开发和优化有前景疗法的潜力。数据和资源代码可在 https://github.com/Zlclab/ACP_DA 上获取。
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引用次数: 0
Aggregate Boid behavior to aid in artificial autopoietic organization 聚集 Boid 行为,帮助人工自生组织。
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-06-01 DOI: 10.1016/j.biosystems.2024.105245
Steven Lawrence, Chrystopher L. Nehaniv

Analyzing carbon-based life on earth can lead to biased inferences on the nature of life as might exist in elsewhere in the universe in alternative forms, therefore, scientists have looked into either abstracting life into constituent systems it is comprised of, or logics of life, or lists of essential criteria, or essential dynamic patterning that characterizes the living. A system-level characterization that is and referred to as a general pattern of minimal life is autopoiesis (Varela et al., 1974) including production, maintenance and replacement of required constituents for setting up and maintaining an internal environment with self/other separation that regulates and is constitutive of processes that produce the environment and components for processes that comprise this ongoing activity of self-production in ‘recursively’, i.e., in a manner that allows the organizational pattern to continually reconstitute the conditions, components and processes required for its own perpetuation. This seminal concept of an autopoiesis is instantiated in life as we know it, but might also be instantiated in different media and in unforeseen ways. Other researchers have argued life is more than autopoiesis and that it is a co-emergent property of autopoiesis and cognition. Life produces many emergent properties such as synchronization and patterns as seen in flocks and herds of different animal species. The mechanics of this synchrony displayed in flocks and herd animals has been extracted by Craig Reynolds into a generative model referred to as “Boids”. With these concepts in mind, we address the following research question: How can the synchronous maneuvers and aggregate behavior of Boids contribute to constitutive subsystems in realizing an autopoietic system? Can such a system exhibit minimal cognition? This work attempts to answer these questions with a bottom-up approach to constructing an artificial life system. We exhibit a computational model of autopoiesis and a minimal level of cognition in the sense of M. Bitbol and P. Luigi Luisi, whereby an autopoietic entity engages in active assimilation of external components as part of its activity of self-production.

对地球上的碳基生命进行分析,可能会导致对宇宙其他地方可能存在的其他形式的生命本质做出有失偏颇的推断,因此,科学家们要么将生命抽象为由其组成的系统,要么将其抽象为生命逻辑,要么将其抽象为基本标准清单,要么将其抽象为描述生命特征的基本动态模式。自生(autopoiesis)(瓦雷拉等人,1974 年)是一个系统层面的特征,也被称为最小生命的一般模式,包括生产、维护和替换所需的成分,以建立和维持一个自我/他体分离的内部环境,该环境调节并构成生产环境的过程,以及构成这一持续的自我生产活动的过程的成分,即以一种允许组织模式不断重组自身永续所需的条件、成分和过程的方式。这一开创性的 "自生 "概念在我们所知的生命中得到了体现,但也可能以不同的媒介和不可预见的方式得到体现。其他研究人员则认为,生命不仅仅是自生过程,它是自生过程和认知的共同生成属性。生命产生了许多新出现的特性,例如同步和模式,这在不同动物物种的成群结队中可以看到。克雷格-雷诺兹(Craig Reynolds)将成群结队的动物所表现出的这种同步性的机理提取为一个生成模型,称为 "Boids"。基于这些概念,我们提出了以下研究问题:Boids 的同步操作和聚合行为如何为实现自造血系统的构成子系统做出贡献?这样的系统能否表现出最低限度的认知?这项研究试图用一种自下而上的方法来构建人工生命系统,从而回答这些问题。我们展示了一个自生的计算模型,以及 M. Bitbol 和 P. Luigi Luisi 意义上的最低认知水平,即自生实体在自我生产活动中主动吸收外部成分。
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引用次数: 0
The effect of avian eggshell membrane structure on microbial penetration: A simulation study 禽蛋壳膜结构对微生物渗透的影响:模拟研究
IF 1.6 4区 生物学 Q1 Mathematics Pub Date : 2024-05-15 DOI: 10.1016/j.biosystems.2024.105234
Seungwoo Sim , Cheol-Min Park , Sang-Hee Lee , Haeun Cho , Youngheum Ji , Heeso Noh , Sang-im Lee

Avian eggshells exhibit excellent antimicrobial properties. In this study, we conducted simulation experiments to explore the defense mechanisms of eggshell membranes with regards to their physical features. We developed a mathematical model for the movement of microorganisms and estimated their penetration ratio into eggshell membranes based on several factors, including membrane thickness, microbial size, directional drift, and attachment probability to membrane fibers. These results not only suggest that an eggshell membrane with multiple layers and low porosity indicates high antimicrobial performance, but also imply that the fibrous network structure of the membrane might contribute to effective defense. Our simulation results aligned with experimental findings, specifically in measuring the penetration time of Escherichia coli through the eggshell membrane. We briefly discuss the significance and limitations of this pilot study, as well as the potential for these results, to serve as a foundation for the development of antimicrobial materials.

禽类蛋壳具有出色的抗菌特性。在本研究中,我们进行了模拟实验,以探索蛋壳膜的物理特性对其防御机制的影响。我们建立了一个微生物运动的数学模型,并根据膜厚度、微生物大小、定向漂移和附着在膜纤维上的概率等几个因素估算了微生物对蛋壳膜的渗透率。这些结果不仅表明,多层、低孔隙率的蛋壳膜具有很高的抗菌性能,而且还意味着膜的纤维网络结构可能有助于有效防御。我们的模拟结果与实验结果一致,特别是在测量大肠杆菌穿透蛋壳膜的时间方面。我们简要讨论了这项试验研究的意义和局限性,以及这些结果作为抗菌材料开发基础的潜力。
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引用次数: 0
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