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Network topology enables efficient response to environment inPhysarum polycephalum. 网络拓扑结构使多头绒泡菌能够有效地响应环境。
IF 2 4区 生物学
Physical biology Pub Date : 2023-05-16 DOI: 10.1088/1478-3975/accef2
Siyu Chen, Karen Alim
{"title":"Network topology enables efficient response to environment in<i>Physarum polycephalum</i>.","authors":"Siyu Chen,&nbsp;Karen Alim","doi":"10.1088/1478-3975/accef2","DOIUrl":"https://doi.org/10.1088/1478-3975/accef2","url":null,"abstract":"<p><p>The network-shaped body plan distinguishes the unicellular slime mould<i>Physarum polycephalum</i>in body architecture from other unicellular organisms. Yet, network-shaped body plans dominate branches of multi-cellular life such as in fungi. What survival advantage does a network structure provide when facing a dynamic environment with adverse conditions? Here, we probe how network topology impacts<i>P. polycephalum</i>'s avoidance response to an adverse blue light. We stimulate either an elongated, I-shaped amoeboid or a Y-shaped networked specimen and subsequently quantify the evacuation process of the light-exposed body part. The result shows that Y-shaped specimen complete the avoidance retraction in a comparable time frame, even slightly faster than I-shaped organisms, yet, at a lower almost negligible increase in migration velocity. Contraction amplitude driving mass motion is further only locally increased in Y-shaped specimen compared to I-shaped-providing further evidence that Y-shaped's avoidance reaction is energetically more efficient than in I-shaped amoeboid organisms. The difference in the retraction behaviour suggests that the complexity of network topology provides a key advantage when encountering adverse environments. Our findings could lead to a better understanding of the transition from unicellular to multicellularity.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9514674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading 通过内化校对的EGF受体配体鉴别定量建模
IF 2 4区 生物学
Physical biology Pub Date : 2023-05-10 DOI: 10.1101/2023.05.09.539827
Jaleesa A Leblanc, Michael G. Sugiyama, C. Antonescu, Aidan I. Brown
{"title":"Quantitative modeling of EGF receptor ligand discrimination via internalization proofreading","authors":"Jaleesa A Leblanc, Michael G. Sugiyama, C. Antonescu, Aidan I. Brown","doi":"10.1101/2023.05.09.539827","DOIUrl":"https://doi.org/10.1101/2023.05.09.539827","url":null,"abstract":"The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology that is stimulated by multiple distinct ligands. Although ligands bind to EGFR while the receptor is exposed on the plasma membrane, EGFR incorporation into endosomes following receptor internalization is an important aspect of EGFR signaling, with EGFR internalization behavior dependent upon the type of ligand bound. We develop quantitative modeling for EGFR recruitment to and internalization from clathrin domains, focusing on how internalization competes with ligand unbinding from EGFR. We develop two model versions: a kinetic model with EGFR behavior described as transitions between discrete states and a spatial model with EGFR diffusion to circular clathrin domains. We find that a combination of spatial and kinetic proofreading leads to enhanced EGFR internalization ratios in comparison to unbinding differences between ligand types. Various stages of the EGFR internalization process, including recruitment to and internalization from clathrin domains, modulate the internalization differences between receptors bound to different ligands. Our results indicate that following ligand binding, EGFR may encounter multiple clathrin domains before successful recruitment and internalization. The quantitative modeling we have developed describes competition between EGFR internalization and ligand unbinding and the resulting proofreading.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45880122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Timescale separation in the coordinated switching of bacterial flagellar motors. 细菌鞭毛马达协调开关的时间尺度分离。
IF 2 4区 生物学
Physical biology Pub Date : 2023-05-10 DOI: 10.1088/1478-3975/acd0fb
Guanhua Yue, Rongjing Zhang, Junhua Yuan
{"title":"Timescale separation in the coordinated switching of bacterial flagellar motors.","authors":"Guanhua Yue,&nbsp;Rongjing Zhang,&nbsp;Junhua Yuan","doi":"10.1088/1478-3975/acd0fb","DOIUrl":"https://doi.org/10.1088/1478-3975/acd0fb","url":null,"abstract":"<p><p>The output of the bacterial chemotaxis signaling pathway, the level of the intracellular regulator CheY-P, modulates the rotation direction of the flagellar motor, thereby regulating bacterial run-and-tumble behavior. The multiple flagellar motors on an<i>E. coli</i>cell are controlled by a common cytoplasmic pool of CheY-P. Fluctuation of the CheY-P level was thought to be able to coordinate the switching of multiple motors. Here, we measured the correlation of rotation directions between two motors on a cell, finding that it surprisingly exhibits two well separated timescales. We found that the slow timescale (∼6 s) can be explained by the slow fluctuation of the CheY-P level due to stochastic activity of the chemotactic adaptation enzymes, whereas the fast timescale (∼0.3 s) can be explained by the random pulse-like fluctuation of the CheY-P level, due probably to the activity of the chemoreceptor clusters. We extracted information on the properties of the fast CheY-P pulses based on the correlation measurements. The two well-separated timescales in the fluctuation of CheY-P level help to coordinate multiple motors on a cell and to enhance bacterial chemotactic performance.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of thermal and athermal dynamics of the cell membrane slope fluctuations in the presence and absence of Latrunculin-B. 有无 Latrunculin-B 作用下细胞膜斜率波动的热动态和非热动态比较。
IF 2 4区 生物学
Physical biology Pub Date : 2023-05-05 DOI: 10.1088/1478-3975/accef1
Srestha Roy, Rahul Vaippully, Muruga Lokesh, Gokul Nalupurackal, Vandana Yadav, Snigdhadev Chakraborty, Manoj Gopalakrishnan, Privita Edwina Rayappan George Edwin, Saumendra Kumar Bajpai, Basudev Roy
{"title":"Comparison of thermal and athermal dynamics of the cell membrane slope fluctuations in the presence and absence of Latrunculin-B.","authors":"Srestha Roy, Rahul Vaippully, Muruga Lokesh, Gokul Nalupurackal, Vandana Yadav, Snigdhadev Chakraborty, Manoj Gopalakrishnan, Privita Edwina Rayappan George Edwin, Saumendra Kumar Bajpai, Basudev Roy","doi":"10.1088/1478-3975/accef1","DOIUrl":"10.1088/1478-3975/accef1","url":null,"abstract":"<p><p>Conventionally, only the normal cell membrane fluctuations have been studied and used to ascertain membrane properties like the bending rigidity. A new concept, the membrane local slope fluctuations was introduced recently (Vaippully<i>et al</i>2020<i>Soft Matter</i><b>16</b>7606), which can be modelled as a gradient of the normal fluctuations. It has been found that the power spectral density (PSD) of slope fluctuations behave as (frequency)<sup>-1</sup>while the normal fluctuations yields (frequency)-5/3even on the apical cell membrane in the high frequency region. In this manuscript, we explore a different situation where the cell is applied with the drug Latrunculin-B which inhibits actin polymerization and find the effect on membrane fluctuations. We find that even as the normal fluctuations show a power law (frequency)-5/3as is the case for a free membrane, the slope fluctuations PSD remains (frequency)<sup>-1</sup>, with exactly the same coefficient as the case when the drug was not applied. Moreover, while sometimes, when the normal fluctuations at high frequency yield a power law of (frequency)-4/3, the pitch PSD still yields (frequency)<sup>-1</sup>. Thus, this presents a convenient opportunity to study membrane parameters like bending rigidity as a function of time after application of the drug, while the membrane softens. We also investigate the active athermal fluctuations of the membrane appearing in the PSD at low frequencies and find active timescales of slower than 1 s.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Module representatives for refining gene co-expression modules. 模块代表提炼基因共表达模块。
IF 2 4区 生物学
Physical biology Pub Date : 2023-05-04 DOI: 10.1088/1478-3975/acce8d
Nathan Mankovich, Helene Andrews-Polymenis, David Threadgill, Michael Kirby
{"title":"Module representatives for refining gene co-expression modules.","authors":"Nathan Mankovich,&nbsp;Helene Andrews-Polymenis,&nbsp;David Threadgill,&nbsp;Michael Kirby","doi":"10.1088/1478-3975/acce8d","DOIUrl":"https://doi.org/10.1088/1478-3975/acce8d","url":null,"abstract":"<p><p>This paper concerns the identification of gene co-expression modules in transcriptomics data, i.e. collections of genes which are highly co-expressed and potentially linked to a biological mechanism. Weighted gene co-expression network analysis (WGCNA) is a widely used method for module detection based on the computation of eigengenes, the weights of the first principal component for the module gene expression matrix. This eigengene has been used as a centroid in a<i>k</i>-means algorithm to improve module memberships. In this paper, we present four new module representatives: the eigengene subspace, flag mean, flag median and module expression vector. The eigengene subspace, flag mean and flag median are subspace module representatives which capture more variance of the gene expression within a module. The module expression vector is a weighted centroid of the module which leverages the structure of the module gene co-expression network. We use these module representatives in Linde-Buzo-Gray clustering algorithms to refine WGCNA module membership. We evaluate these methodologies on two transcriptomics data sets. We find that most of our module refinement techniques improve upon the WGCNA modules by two statistics: (1) module classification between phenotype and (2) module biological significance according to Gene Ontology terms.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9789099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Theoretical understanding of evolutionary dynamics on inhomogeneous networks. 非均匀网络上进化动力学的理论认识。
IF 2 4区 生物学
Physical biology Pub Date : 2023-04-21 DOI: 10.1088/1478-3975/accb36
Hamid Teimouri, Dorsa B Sattari Khavas, Cade Spaulding, Christopher B Li, Anatoly B Kolomeisky
{"title":"Theoretical understanding of evolutionary dynamics on inhomogeneous networks.","authors":"Hamid Teimouri,&nbsp;Dorsa B Sattari Khavas,&nbsp;Cade Spaulding,&nbsp;Christopher B Li,&nbsp;Anatoly B Kolomeisky","doi":"10.1088/1478-3975/accb36","DOIUrl":"https://doi.org/10.1088/1478-3975/accb36","url":null,"abstract":"<p><p>Evolution is the main feature of all biological systems that allows populations to change their characteristics over successive generations. A powerful approach to understand evolutionary dynamics is to investigate fixation probabilities and fixation times of novel mutations on networks that mimic biological populations. It is now well established that the structure of such networks can have dramatic effects on evolutionary dynamics. In particular, there are population structures that might amplify the fixation probabilities while simultaneously delaying the fixation events. However, the microscopic origins of such complex evolutionary dynamics remain not well understood. We present here a theoretical investigation of the microscopic mechanisms of mutation fixation processes on inhomogeneous networks. It views evolutionary dynamics as a set of stochastic transitions between discrete states specified by different numbers of mutated cells. By specifically considering star networks, we obtain a comprehensive description of evolutionary dynamics. Our approach allows us to employ physics-inspired free-energy landscape arguments to explain the observed trends in fixation times and fixation probabilities, providing a better microscopic understanding of evolutionary dynamics in complex systems.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Network topology enables efficient response to environment in Physarum polycephalum 网络拓扑结构能够有效应对多头绒泡菌的环境
IF 2 4区 生物学
Physical biology Pub Date : 2023-04-11 DOI: 10.1101/2022.11.09.515897
Siyu Chen, K. Alim
{"title":"Network topology enables efficient response to environment in Physarum polycephalum","authors":"Siyu Chen, K. Alim","doi":"10.1101/2022.11.09.515897","DOIUrl":"https://doi.org/10.1101/2022.11.09.515897","url":null,"abstract":"The network-shaped body plan distinguishes the unicellular slime mould Physarum polycephalum in body architecture from other unicellular organisms. Yet, network-shaped body plans dominate branches of multi-cellular life such as in fungi. What survival advantage does a network structure provide when facing a dynamic environment with adverse conditions? Here, we probe how network topology impacts P. polycephalum’s avoidance response to an adverse blue light. We stimulate either an elongated, I-shaped amoeboid or a Y-shaped networked specimen and subsequently quantify the evacuation process of the light-exposed body part. The result shows that Y-shaped specimen complete the avoidance retraction in a comparable time frame, even slightly faster than I-shaped organisms, yet, at a lower almost negligible increase in migration velocity. Contraction amplitude driving mass motion is further only locally increased in Y-shaped specimen compared to I-shaped—providing further evidence that Y-shaped’s avoidance reaction is energetically more efficient than in I-shaped amoeboid organisms. The difference in the retraction behaviour suggests that the complexity of network topology provides a key advantage when encountering adverse environments. Our findings could lead to a better understanding of the transition from unicellular to multicellularity.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49500103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Collective response to local perturbations: how to evade threats without losing coherence. 对局部扰动的集体反应:如何在不失去连贯性的情况下逃避威胁。
IF 2 4区 生物学
Physical biology Pub Date : 2023-04-11 DOI: 10.1088/1478-3975/acc5cc
Emanuele Loffredo, Davide Venturelli, Irene Giardina
{"title":"Collective response to local perturbations: how to evade threats without losing coherence.","authors":"Emanuele Loffredo,&nbsp;Davide Venturelli,&nbsp;Irene Giardina","doi":"10.1088/1478-3975/acc5cc","DOIUrl":"https://doi.org/10.1088/1478-3975/acc5cc","url":null,"abstract":"<p><p>Living groups move in complex environments and are constantly subject to external stimuli, predatory attacks and disturbances. An efficient response to such perturbations is vital to maintain the group's coherence and cohesion. Perturbations are often local, i.e. they are initially perceived only by few individuals in the group, but can elicit a global response. This is the case of starling flocks, that can turn very quickly to evade predators. In this paper, we investigate the conditions under which a global change of direction can occur upon local perturbations. Using minimal models of self-propelled particles, we show that a collective directional response occurs on timescales that grow with the system size and it is, therefore, a finite-size effect. The larger the group is, the longer it will take to turn. We also show that global coherent turns can only take place if i) the mechanism for information propagation is efficient enough to transmit the local reaction undamped through the whole group; and if ii) motility is not too strong, to avoid that the perturbed individual leaves the group before the turn is complete. No compliance with such conditions results in the group's fragmentation or in a non-efficient response.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9408711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Computer simulation reveals the effect of severing enzymes on dynamic and stabilized microtubules. 计算机模拟揭示了切断酶对动态稳定微管的影响。
IF 2 4区 生物学
Physical biology Pub Date : 2023-04-03 DOI: 10.1088/1478-3975/acc301
Aritra Sen, Ambarish Kunwar
{"title":"Computer simulation reveals the effect of severing enzymes on dynamic and stabilized microtubules.","authors":"Aritra Sen,&nbsp;Ambarish Kunwar","doi":"10.1088/1478-3975/acc301","DOIUrl":"https://doi.org/10.1088/1478-3975/acc301","url":null,"abstract":"<p><p>Microtubule (MT) severing enzymes Katanin and Spastin cut the MT into smaller fragments and are being studied extensively using<i>in-vitro</i>experiments due to their crucial role in different cancers and neurodevelopmental disorders. It has been reported that the severing enzymes are either involved in increasing or decreasing the tubulin mass. Currently, there are a few analytical and computational models for MT amplification and severing. However, these models do not capture the action of MT severing explicitly, as these are based on partial differential equations in one dimension. On the other hand, a few discrete lattice-based models were used earlier to understand the activity of severing enzymes only on stabilized MTs. Hence, in this study, discrete lattice-based Monte Carlo models that included MT dynamics and severing enzyme activity have been developed to understand the effect of severing enzymes on tubulin mass, MT number, and MT length. It was found that the action of severing enzyme reduces average MT length while increasing their number; however, the total tubulin mass can decrease or increase depending on the concentration of GMPCPP (Guanylyl-(<i>α</i>,<i>β</i>)-methylene-diphosphonate)-which is a slowly hydrolyzable analogue of GTP (Guanosine triphosphate). Further, relative tubulin mass also depends on the detachment ratio of GTP/GMPCPP and Guanosine diphosphate tubulin dimers and the binding energies of tubulin dimers covered by the severing enzyme.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"20 3","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9408683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rapid prediction of lab-grown tissue properties using deep learning 利用深度学习快速预测实验室培养的组织特性
IF 2 4区 生物学
Physical biology Pub Date : 2023-03-31 DOI: 10.48550/arXiv.2303.18017
Allison E. Andrews, H. Dickinson, J. Hague
{"title":"Rapid prediction of lab-grown tissue properties using deep learning","authors":"Allison E. Andrews, H. Dickinson, J. Hague","doi":"10.48550/arXiv.2303.18017","DOIUrl":"https://doi.org/10.48550/arXiv.2303.18017","url":null,"abstract":"The interactions between cells and the extracellular matrix are vital for the self-organisation of tissues. In this paper we present proof-of-concept to use machine learning tools to predict the role of this mechanobiology in the self-organisation of cell-laden hydrogels grown in tethered moulds. We develop a process for the automated generation of mould designs with and without key symmetries. We create a large training set with $N=6400$ cases by running detailed biophysical simulations of cell-matrix interactions using the contractile network dipole orientation (CONDOR) model for the self-organisation of cellular hydrogels within these moulds. These are used to train an implementation of the texttt{pix2pix} deep learning model, with an additional $100$ cases that were unseen in the training of the neural network for review and testing of the trained model. Comparison between the predictions of the machine learning technique and the reserved predictions from the biophysical algorithm show that the machine learning algorithm makes excellent predictions. The machine learning algorithm is significantly faster than the biophysical method, opening the possibility of very high throughput rational design of moulds for pharmaceutical testing, regenerative medicine and fundamental studies of biology. Future extensions for scaffolds and 3D bioprinting will open additional applications.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"1 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44964745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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