Articoli di riviste: "Dynamic Cell Clustering (DCC)"

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Wang, Zheng, Lara M. Linden, Kaleb M. Naegeli, Joshua W. Ziel, Qiuyi Chi, Elliott J. Hagedorn, Natasha S. Savage e David R. Sherwood. "UNC-6 (netrin) stabilizes oscillatory clustering of the UNC-40 (DCC) receptor to orient polarity". Journal of Cell Biology 206, n. 5 (25 agosto 2014): 619–33. http://dx.doi.org/10.1083/jcb.201405026.

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The receptor deleted in colorectal cancer (DCC) directs dynamic polarizing activities in animals toward its extracellular ligand netrin. How DCC polarizes toward netrin is poorly understood. By performing live-cell imaging of the DCC orthologue UNC-40 during anchor cell invasion in Caenorhabditis elegans, we have found that UNC-40 clusters, recruits F-actin effectors, and generates F-actin in the absence of UNC-6 (netrin). Time-lapse analyses revealed that UNC-40 clusters assemble, disassemble, and reform at periodic intervals in different regions of the cell membrane. This oscillatory behavior indicates that UNC-40 clusters through a mechanism involving interlinked positive (formation) and negative (disassembly) feedback. We show that endogenous UNC-6 and ectopically provided UNC-6 orient and stabilize UNC-40 clustering. Furthermore, the UNC-40–binding protein MADD-2 (a TRIM family protein) promotes ligand-independent clustering and robust UNC-40 polarization toward UNC-6. Together, our data suggest that UNC-6 (netrin) directs polarized responses by stabilizing UNC-40 clustering. We propose that ligand-independent UNC-40 clustering provides a robust and adaptable mechanism to polarize toward netrin.

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Alammari, Amr A., Mohd Sharique, Athar Ali Moinuddin e Mohammad Samar Ansari. "Local-Partial Signal Combining Schemes for Cell-Free Large-Scale MU-MIMO Systems with Limited Fronthaul Capacity and Spatial Correlation Channels". Electronics 11, n. 17 (1 settembre 2022): 2757. http://dx.doi.org/10.3390/electronics11172757.

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Cell-free large-scale multi-user MIMO is a promising technology for the 5G-and-beyond mobile communication networks. Scalable signal processing is the key challenge in achieving the benefits of cell-free systems. This study examines a distributed approach for cell-free deployment with user-centric configuration and finite fronthaul capacity. Moreover, the impact of scaling the pilot length, the number of access points (APs), and the number of antennas per AP on the achievable average spectral efficiency are investigated. Using the dynamic cooperative clustering (DCC) technique and large-scale fading decoding process, we derive an approximation of the signal-to-interference-plus-noise ratio in the criteria of two local combining schemes: Local-Partial Regularized Zero Forcing (RZF) and Local Maximum Ratio (MR). The results indicate that distributed approaches in the cell-free system have the advantage of decreasing the fronthaul signaling and the computing complexity. The results also show that the Local-Partial RZF provides the highest average spectral efficiency among all the distributed combining schemes because the computational complexity of the Local-Partial RZF is independent of the UTs. Therefore, it does not grow as the number of user terminals (UTs) increases.

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Peters, Georg, e Richard Weber. "DCC: a framework for dynamic granular clustering". Granular Computing 1, n. 1 (4 febbraio 2016): 1–11. http://dx.doi.org/10.1007/s41066-015-0012-z.

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FOWLER, ANNA, VILAS MENON e NICHOLAS A. HEARD. "DYNAMIC BAYESIAN CLUSTERING". Journal of Bioinformatics and Computational Biology 11, n. 05 (ottobre 2013): 1342001. http://dx.doi.org/10.1142/s0219720013420018.

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Clusters of time series data may change location and memberships over time; in gene expression data, this occurs as groups of genes or samples respond differently to stimuli or experimental conditions at different times. In order to uncover this underlying temporal structure, we consider dynamic clusters with time-dependent parameters which split and merge over time, enabling cluster memberships to change. These interesting time-dependent structures are useful in understanding the development of organisms or complex organs, and could not be identified using traditional clustering methods. In cell cycle data, these time-dependent structure may provide links between genes and stages of the cell cycle, whilst in developmental data sets they may highlight key developmental transitions.

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Dai, Yun, e Hao Liu. "Application of the R-Tree Clustering Model in Medical Information Retrieval". Mobile Information Systems 2022 (11 agosto 2022): 1–9. http://dx.doi.org/10.1155/2022/2887395.

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Hospitals produce a large amount of medical information every day. In the face of medical big data, the existing data processing methods cannot meet expectations and need to be continuously optimized. In the database system, when the stored objects are very large, and then the efficiency of data retrieval is a major bottleneck, therefore restricting the application of medical information. For that reason and to improve the efficiency of information retrieval, it is necessary to add an index to the information object and filter the dataset participating in the connection retrieval through the index. In this paper, an information retrieval technique grounded on the R-tree clustering model index is proposed for massive hospital information. The R-tree clustering model is constructed in massive hospital information by using the dynamic determination clustering center (DCC) algorithm. Finally, the superiority of the method is proved by simulations. The experiments and empirical evaluation show that the proposed R-tree clustering model index significantly improves data retrieval efficiency.

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Stavoe, Andrea K. H., e Daniel A. Colón-Ramos. "Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton". Journal of Cell Biology 197, n. 1 (26 marzo 2012): 75–88. http://dx.doi.org/10.1083/jcb.201110127.

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Netrin is a chemotrophic factor known to regulate a number of neurodevelopmental processes, including cell migration, axon guidance, and synaptogenesis. Although the role of Netrin in synaptogenesis is conserved throughout evolution, the mechanisms by which it instructs synapse assembly are not understood. Here we identify a mechanism by which the Netrin receptor UNC-40/DCC instructs synaptic vesicle clustering in vivo. UNC-40 localized to presynaptic regions in response to Netrin. We show that UNC-40 interacted with CED-5/DOCK180 and instructed CED-5 presynaptic localization. CED-5 in turn signaled through CED-10/Rac1 and MIG-10/Lamellipodin to organize the actin cytoskeleton in presynaptic regions. Localization of this signaling pathway to presynaptic regions was necessary for synaptic vesicle clustering during synapse assembly but not for the subcellular localization of active zone proteins. Thus, vesicle clustering and localization of active zone proteins are instructed by separate pathways downstream of Netrin. Our data indicate that signaling modules known to organize the actin cytoskeleton during guidance can be co-opted to instruct synaptic vesicle clustering.

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Kaneko, Kunihiko, e Tetsuya Yomo. "Cell division, differentiation and dynamic clustering". Physica D: Nonlinear Phenomena 75, n. 1-3 (agosto 1994): 89–102. http://dx.doi.org/10.1016/0167-2789(94)90277-1.

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Yan, Kejia, Huqin Yan e Rakesh Gupta. "Are GARCH and DCC Values of 10 Cryptocurrencies Affected by COVID-19?" Journal of Risk and Financial Management 15, n. 3 (1 marzo 2022): 113. http://dx.doi.org/10.3390/jrfm15030113.

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This paper examines the dynamic conditional correlations among 10 cryptocurrencies and the possibility of hedging investment strategies among multiple cryptocurrencies over the period affected by COVID-19 from 2017 to 2022. After studying the relationship between Bitcoin, Ethereum, and the other eight cryptocurrencies, four main results were obtained in this paper: first, from the pre-COVID-19 period to the COVID-19 period, almost all of the cryptocurrencies’ return growth rates increased, and COVID-19 had a positive effect on the returns of cryptocurrencies. Second, all of the cryptocurrencies’ return indices had features of volatility clustering and memory persistence in the long run; from pre-COVID-19 to COVID-19, these cryptocurrencies’ GARCH values decreased, but the correlations among the varying GARCH values increased. Third, the varying correlations between the return indices of Bitcoin, Ethereum, and the other cryptocurrencies were very strong; from pre-COVID-19 to COVID-19, the average dynamic correlations between Bitcoin and the others increased. Fourth, Tether can be used as a hedge cryptocurrency against the other cryptocurrencies as COVID-19 enhanced its hedging feature.

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Ahmad, Burhan, Ole Gjølberg e Mubashir Mehdi. "Spatial Differences in Rice Price Volatility: A Case Study of Pakistan 1994–2011". Pakistan Development Review 56, n. 3 (1 settembre 2017): 265–89. http://dx.doi.org/10.30541/v56i3pp.265-289.

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Prices of agricultural commodities tend to be more volatile in comparison to other commodities. Volatility can result in inefficient allocation of the resources by the farmers, traders and consumers. Rice is the second major staple and export item of Pakistan. This study presents the trends in volatility of regional rice markets of Pakistan and analyses spatial differences in volatility across regional rice markets in Pakistan from 1994 to 2011, and also draws comparison of volatility with the international market. ARCH-LM tests are applied to check the presence of volatility and volatility clustering is found in all the markets. Tests for equality of variance and dynamic conditional correlations (DCC) GARCH model are employed to analyse the spatial differences across the regional rice markets of Pakistan. The results indicate the presence of spatial differences in volatility. Positive conditional correlations in the dynamic conditional correlations (DCC) GARCH model are found which indicate positive association of volatility across markets. Spatial differences in volatility and its persistence reflect the differences in market forces, infrastructure and information flow which leads to varying degree of risk across markets and some regions are exposed to higher risk. The study found out that Hyderabad and Sukkur are the most volatile markets and their volatility levels are highly persistent and require highest time to return to its long-term mean which makes them the riskiest rice markets. Investments in infrastructure, particularly in transportation and controlling the market power of middlemen may reduce price risk across markets particularly in the most risky markets. JEL Classification: C22, C32, Q11, Q13, Q18 Keywords: Rice Prices Volatility, Regional Markets, Pakistan. DCC-GARCH-models

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Raya, Elia, Huiqin Koerkel-Qu, Laura Rudhart, Lisa-Marie Köhler, Anna Damboeck, Christoph Irlbeck, Catherine Botteron, Melanie Werner-Klein, Stephan Seitz e Christoph Klein. "Abstract 3788: EpCAM+ DCCs isolated from the bone marrow of breast cancer patients display high stemness and potency scores". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 3788. http://dx.doi.org/10.1158/1538-7445.am2024-3788.

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Abstract Metastatic dissemination of cancer cells from primary to distant sites often occurs early and it has been shown that their detection is linked to poor outcomes. Eradication of disseminated cancer cells (DCC) has therefore become the primary goal of adjuvant therapies. Since the phenotype of DCC is largely unknown, we set out to search, isolate, and molecularly characterize these candidate metastasis founder cells from bone marrow of breast cancer patients, years before manifestation of metastasis. We screened more than 200 bone marrow samples of breast cancer patients with no evident metastasis (UICC stage M0) for EpCAM-positive cells. EpCAM positive cells in the bone marrow of healthy donors were used as a negative control. In addition, we isolated DCC from breast cancer patients with manifest metastasis (UICC stage M1). We then performed single cell RNA sequencing after whole transcriptome amplification of the collected DCC and the healthy donor (HD) control cells. To confirm the malignant origin of picked DCCs, we projected the transcriptome data into the bone marrow atlas, inferred copy number alterations, and searched for mutations shared with the matched primary tumor. EpCAM-positive cells from control patients mostly comprised plasma cells. In contrast, DCCs derived from M0-stage breast cancer patient formed a unique, non-overlapping cluster in the bone marrow atlas. UMAP-clustering placed M1-stage DCC clearly separate from M0 stage DCC. Among the collected M0-stage DCCs, we identified at least three separate subclusters. Strikingly, M0-stage DCC displayed much higher stemness and potency scores than M1-stage DCCs, reminiscent of embryonic cells. DCCs, identified by EpCAM, display very high transcriptional stemness scores when isolated before metastatic manifestation. Upon expansion and proliferation, stemness scores are reduced indicating epithelial re-differentiation. The embryonic phenotype of M0-stage DCCs may reflect an early adaptive mechanism that enables DCC to survive in an ectopic environment and may impact on the metastatic potential of the DCC. Citation Format: Elia Raya, Huiqin Koerkel-Qu, Laura Rudhart, Lisa-Marie Köhler, Anna Damboeck, Christoph Irlbeck, Catherine Botteron, Melanie Werner-Klein, Stephan Seitz, Christoph Klein. EpCAM+ DCCs isolated from the bone marrow of breast cancer patients display high stemness and potency scores [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3788.

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DeGeer, Jonathan, Andrew Kaplan, Pierre Mattar, Morgane Morabito, Ursula Stochaj, Timothy E. Kennedy, Anne Debant, Michel Cayouette, Alyson E. Fournier e Nathalie Lamarche-Vane. "Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by netrin-1". Journal of Cell Biology 210, n. 5 (31 agosto 2015): 817–32. http://dx.doi.org/10.1083/jcb.201505084.

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During development, netrin-1 is both an attractive and repulsive axon guidance cue and mediates its attractive function through the receptor Deleted in Colorectal Cancer (DCC). The activation of Rho guanosine triphosphatases within the extending growth cone facilitates the dynamic reorganization of the cytoskeleton required to drive axon extension. The Rac1 guanine nucleotide exchange factor (GEF) Trio is essential for netrin-1–induced axon outgrowth and guidance. Here, we identify the molecular chaperone heat shock cognate protein 70 (Hsc70) as a novel Trio regulator. Hsc70 dynamically associated with the N-terminal region and Rac1 GEF domain of Trio. Whereas Hsc70 expression supported Trio-dependent Rac1 activation, adenosine triphosphatase–deficient Hsc70 (D10N) abrogated Trio Rac1 GEF activity and netrin-1–induced Rac1 activation. Hsc70 was required for netrin-1–mediated axon growth and attraction in vitro, whereas Hsc70 activity supported callosal projections and radial neuronal migration in the embryonic neocortex. These findings demonstrate that Hsc70 chaperone activity is required for Rac1 activation by Trio and this function underlies netrin-1/DCC-dependent axon outgrowth and guidance.

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Pateromichelakis, Emmanouil, Mehrdad Shariat, Attaul Quddus, Mehrdad Dianati e Rahim Tafazolli. "Dynamic Clustering Framework for Multi-Cell Scheduling in Dense Small Cell Networks". IEEE Communications Letters 17, n. 9 (settembre 2013): 1802–5. http://dx.doi.org/10.1109/lcomm.2013.072313.131248.

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Maruta, Kazuki. "Dynamic Clustering and Coordinated User Scheduling for Cooperative Interference Cancellation on Ultra-High Density Distributed Antenna Systems". Entropy 20, n. 8 (19 agosto 2018): 616. http://dx.doi.org/10.3390/e20080616.

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This paper proposes dynamic clustering and user scheduling for previously conceived inter-cluster interference cancellation scheme on ultra-high density distributed antenna system (UHD-DAS). UHD-DAS is composed of one central unit (CU) and densely deployed remote radio units (RUs) serving as small cell access points. It can enhance spatial spectral efficiency by alleviating traffic load imposed per radio unit; however, intenser small cell deployment revives the inter-cell interference (ICI) problem. Cell clustering, cooperation of multiple RUs, can mitigate ICI partially, whereas inter-cluster interference (ICLI) still limits its possible capacity. Simplified ICLI cancellation based on localized RU cooperation was previously proposed to mitigate interference globally. The resolved issue is that it required frequency reuse distance to fully obtain its interference cancellation ability. This paper introduces dynamic clustering with coordinated user scheduling to ensure reuse distance without extra frequency reuse. Joint dynamic clustering and ICLI cancellation can effectively work and almost reaches ideal performance as full cooperative spatial multiplexing transmission.

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ŞAHİN, Cumhur. "EXAMINATION OF VOLATILITY STRUCTURE BETWEEN TURKISH STOCK MARKET AND COMMODITY MARKETS: A PERSPECTIVE FOR THE PERIOD OF 2015-2019". Business & Management Studies: An International Journal 8, n. 1 (25 marzo 2020): 351–70. http://dx.doi.org/10.15295/bmij.v8i1.1418.

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Commodity markets, both in the past and in modern times, have had an extraordinary economic impact on individuals and societies. Although it is not known exactly when and where commodity markets started, it is thought that it started about 6000 years ago with rice trade in China. Commodities, as raw material providers used in production, have an intensive usage area. This study aims to examine the global commodity prices such as gold ounce price, silver ounce price, copper price, Brent crude oil price, and natural gas prices, and the volatility structure in the Borsa Istanbul 100 index, representing the Turkey Stock Market. For this purpose, daily closing prices for the period of 2015 January-2019 December were examined in the study. To investigate the time evolution of correlations between the commodities and stock market, the dynamic conditional correlation (DCC) GARCH model is used. The results show that the volatility between the BIST 100 index and commodity prices has constant effects and a comprehensive volatility clustering arises.

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Morgunova, Alice, Irina Pokhvisneva, Saara Nolvi, Sonja Entringer, Pathik Wadhwa, John Gilmore, Martin Styner et al. "DCC gene network in the prefrontal cortex is associated with total brain volume in childhood". Journal of Psychiatry & Neuroscience 46, n. 1 (1 gennaio 2020): E154—E163. http://dx.doi.org/10.1503/jpn.200081.

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Background: Genetic variation in the guidance cue DCC gene is linked to psychopathologies involving dysfunction in the prefrontal cortex. We created an expression-based polygenic risk score (ePRS) based on the DCC coexpression gene network in the prefrontal cortex, hypothesizing that it would be associated with individual differences in total brain volume. Methods: We filtered single nucleotide polymorphisms (SNPs) from genes coexpressed with DCC in the prefrontal cortex obtained from an adult postmortem donors database (BrainEAC) for genes enriched in children 1.5 to 11 years old (BrainSpan). The SNPs were weighted by their effect size in predicting gene expression in the prefrontal cortex, multiplied by their allele number based on an individual’s genotype data, and then summarized into an ePRS. We evaluated associations between the DCC ePRS and total brain volume in children in 2 community-based cohorts: the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) and University of California, Irvine (UCI) projects. For comparison, we calculated a conventional PRS based on a genome-wide association study of total brain volume. Results: Higher ePRS was associated with higher total brain volume in children 8 to 10 years old (β = 0.212, p = 0.043; n = 88). The conventional PRS at several different thresholds did not predict total brain volume in this cohort. A replication analysis in an independent cohort of newborns from the UCI study showed an association between the ePRS and newborn total brain volume (β = 0.101, p = 0.048; n = 80). The genes included in the ePRS demonstrated high levels of coexpression throughout the lifespan and are primarily involved in regulating cellular function. Limitations: The relatively small sample size and age differences between the main and replication cohorts were limitations. Conclusion: Our findings suggest that the DCC coexpression network in the prefrontal cortex is critically involved in whole brain development during the first decade of life. Genes comprising the ePRS are involved in gene translation control and cell adhesion, and their expression in the prefrontal cortex at different stages of life provides a snapshot of their dynamic recruitment.

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Nelissen, Judith M. D. T., Inge M. Peters, Bart G. de Grooth, Yvette van Kooyk e Carl G. Figdor. "Dynamic Regulation of Activated Leukocyte Cell Adhesion Molecule–mediated Homotypic Cell Adhesion through the Actin Cytoskeleton". Molecular Biology of the Cell 11, n. 6 (giugno 2000): 2057–68. http://dx.doi.org/10.1091/mbc.11.6.2057.

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Restricted expression of activated leukocyte cell adhesion molecule (ALCAM) by hematopoietic cells suggests an important role in the immune system and hematopoiesis. To get insight into the mechanisms that control ALCAM-mediated adhesion we have investigated homotypic ALCAM–ALCAM interactions. Here, we demonstrate that the cytoskeleton regulates ALCAM-mediated cell adhesion because inhibition of actin polymerization by cytochalasin D (CytD) strongly induces homotypic ALCAM–ALCAM interactions. This induction of cell adhesion is likely due to clustering of ALCAM at the cell surface, which is observed after CytD treatment. Single-particle tracking demonstrated that the lateral mobility of ALCAM in the cell membrane is increased 30-fold after CytD treatment. In contrast, both surface distribution and adhesion of a glycosylphosphatidylinositol (GPI)-anchored ALCAM mutant are insensitive to CytD, despite the increase in lateral mobility of GPI-ALCAM upon CytD treatment. This demonstrates that clustering of ALCAM is essential for cell adhesion, whereas enhanced diffusion of ALCAM alone is not sufficient for cluster formation. In addition, upon ligand binding, both free diffusion and the freely dragged distance of wild-type ALCAM, but not of GPI-ALCAM, are reduced over time, suggesting strengthening of the cytoskeleton linkage. From these findings we conclude that activation of ALCAM-mediated adhesion is dynamically regulated through actin cytoskeleton-dependent clustering.

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Wilhelmsson, Pär, Edward Sjödin, André Wästlund, Jörgen Wallerman, Tomas Lämås e Karin Öhman. "Dynamic treatment units in forest planning using cell proximity". Canadian Journal of Forest Research 51, n. 7 (luglio 2021): 1065–71. http://dx.doi.org/10.1139/cjfr-2020-0210.

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In forest management planning, the dynamic treatment unit (DTU) approach has become an increasingly relevant alternative to the traditional planning approach using fixed stands, due to improved remote sensing techniques and optimization procedures, with the potential for the higher goal fulfillment of forest activities. For the DTU approach, the traditional concept of fixed stands is disregarded, and forest data are kept in units with a high spatial resolution. Forest operations are planned by clustering cells to form treatment units for harvest operations. This paper presents a new model with an exact optimization technique for forming DTUs in forest planning. In comparison with most previous models, this model aims for increased flexibility by modelling the spatial dimension according to cell proximity rather than immediate adjacency. The model is evaluated using a case study with harvest flow constraints for a forest estate in southern Sweden, represented by 3587 cells. The parameter settings differed between cases, resulting in varying degrees of clustered DTUs, which caused relative net present value losses of up to 4.3%. The case without clustering had the lowest net present value when considering entry costs. The solution times varied between 2.2 s and 42 min 6 s and grew rapidly with increasing problem size.

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Shi, Jianfeng, Ming Chen, Wence Zhang, Zhaohui Yang e Hao Xu. "Dynamic AP Clustering and Precoding for User-Centric Virtual Cell Networks". IEEE Transactions on Communications 67, n. 3 (marzo 2019): 2504–16. http://dx.doi.org/10.1109/tcomm.2018.2883290.

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Samarakoon, Sumudu, Mehdi Bennis, Walid Saad e Matti Latva-aho. "Dynamic Clustering and on/off Strategies for Wireless Small Cell Networks". IEEE Transactions on Wireless Communications 15, n. 3 (marzo 2016): 2164–78. http://dx.doi.org/10.1109/twc.2015.2499182.

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Sun, Yubo, Weihua Gui, Xiaofang Chen, Yongfang Xie, Shiwen Xie e Zhong Zou. "A dynamic spatial distributed information clustering method for aluminum electrolysis cell". Engineering Applications of Artificial Intelligence 126 (novembre 2023): 106793. http://dx.doi.org/10.1016/j.engappai.2023.106793.

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Yang, Faguo, e Tianzi Jiang. "Cell Image Segmentation with Kernel-Based Dynamic Clustering and an Ellipsoidal Cell Shape Model". Journal of Biomedical Informatics 34, n. 2 (aprile 2001): 67–73. http://dx.doi.org/10.1006/jbin.2001.1009.

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Yogaswara, Y., T. T. Dimiyati e R. R. Asri. "Grouping Maching using Genetic Algorithm for Dynamic Cell Layout Design". Journal of Modern Manufacturing Systems and Technology 6, n. 1 (31 marzo 2022): 1–8. http://dx.doi.org/10.15282/jmmst.v6i1.6893.

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Changes in the manufacturing sector due to changes in shorter product life cycles, market demands and also use of the latest technology in the company, this will result in changes in process flow and also change the layout in the production section, causing dynamic layout problems. Dynamic layout problems can be solved by using a manufacturing cell formation method which has a high degree of flexibility. In this study, algorithms used for grouping machines into manufacturing cells are Direct Clustering Algorithm and Rank Order Clustering. Then it will be improved by using Genetic Algorithm. The Dynamic Modified Spanning Tree Algorithm is also used to sort machines into a layout with a single-row structure and determine the length of the planning time window in the future. The goals of this research is to get the best solution from the two methods of grouping machines/parts into manufacturing cells and to obtain improvement results using Genetic Algorithms. For the design industry, the resulting dynamic cell layout is expected to reduce production costs, save material handling, be efficient in material flow, which in turn will be able to compete globally.

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Guo, Ling Li, Mu Shu Wang e Ye Wang. "Cell Mapping Modeling for Complex Systems Based on ISODATA Algorithm". Applied Mechanics and Materials 873 (novembre 2017): 332–36. http://dx.doi.org/10.4028/www.scientific.net/amm.873.332.

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This paper presents a new type of modeling framework for complex dynamical systems based on cell mapping. The systems considered are difficult in modeling by physical principle due to complex mechanism. By the method of data driven, the cell mapping model is constructed and the modeling objective is describing statistical dynamic trajectory for this kind of complex system, which overcome the difficulties found in mechanism modeling. Firstly, the clustering of operation modes is achieved by Self-Organizing Data Analysis Techniques Algorithm (ISODATA). Then, a cell division measure is obtained by the clustering result, which is different from the regular partition in other measures. Meanwhile, each class bound is treated as a cell bound, and hence the dynamic trajectory of complex systems is described by the cell mapping. Finally, a simulated experience illustrates the feasibility of the proposed approach.

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Song, Min, Xiaohua Hu, Illhoi Yoo e Eric Koppel. "A Dynamic and Semantically-Aware Technique for Document Clustering in Biomedical Literature". International Journal of Data Warehousing and Mining 5, n. 4 (ottobre 2009): 44–57. http://dx.doi.org/10.4018/jdwm.2009080703.

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As an unsupervised learning process, document clustering has been used to improve information retrieval performance by grouping similar documents and to help text mining approaches by providing a high-quality input for them. In this article, the authors propose a novel hybrid clustering technique that incorporates semantic smoothing of document models into a neural network framework. Recently, it has been reported that the semantic smoothing model enhances the retrieval quality in Information Retrieval (IR). Inspired by that, the authors developed and applied a context-sensitive semantic smoothing model to boost accuracy of clustering that is generated by a dynamic growing cell structure algorithm, a variation of the neural network technique. They evaluated the proposed technique on biomedical article sets from MEDLINE, the largest biomedical digital library in the world. Their experimental evaluations show that the proposed algorithm significantly improves the clustering quality over the traditional clustering techniques including k-means and self-organizing map (SOM).

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Wehrens, Martijn, Pieter Rein ten Wolde e Andrew Mugler. "Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes". Journal of Chemical Physics 141, n. 20 (28 novembre 2014): 205102. http://dx.doi.org/10.1063/1.4901888.

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Zhang, Zhe, Ning Wang, Jiankang Zhang e Xiaomin Mu. "Dynamic User-Centric Clustering for Uplink Cooperation in Multi-Cell Wireless Networks". IEEE Access 6 (2018): 8526–38. http://dx.doi.org/10.1109/access.2018.2792222.

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Wu, Xiwei, e T. Gregory Dewey. "Cluster Analysis of Dynamic Parameters of Gene Expression". Journal of Bioinformatics and Computational Biology 01, n. 03 (ottobre 2003): 447–58. http://dx.doi.org/10.1142/s0219720003000307.

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Cluster analysis has proven to be a valuable statistical method for analyzing whole genome expression data. Although clustering methods have great utility, they do represent a lower level statistical analysis that is not directly tied to a specific model. To extend such methods and to allow for more sophisticated lines of inference, we use cluster analysis in conjunction with a specific model of gene expression dynamics. This model provides phenomenological dynamic parameters on both linear and non-linear responses of the system. This analysis determines the parameters of two different transition matrices (linear and nonlinear) that describe the influence of one gene expression level on another. Using yeast cell cycle microarray data as test set, we calculated the transition matrices and used these dynamic parameters as a metric for cluster analysis. Hierarchical cluster analysis of this transition matrix reveals how a set of genes influence the expression of other genes activated during different cell cycle phases. Most strikingly, genes in different stages of cell cycle preferentially activate or inactivate genes in other stages of cell cycle, and this relationship can be readily visualized in a two-way clustering image. The observation is prior to any knowledge of the chronological characteristics of the cell cycle process. This method shows the utility of using model parameters as a metric in cluster analysis.

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Prikhodko, Ivan V., e Georgy Th Guria. "Dynamic Effects in Nucleation of Receptor Clusters". Entropy 23, n. 10 (24 settembre 2021): 1245. http://dx.doi.org/10.3390/e23101245.

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Nucleation theory has been widely applied for the interpretation of critical phenomena in nonequilibrium systems. Ligand-induced receptor clustering is a critical step of cellular activation. Receptor clusters on the cell surface are treated from the nucleation theory point of view. The authors propose that the redistribution of energy over the degrees of freedom is crucial for forming each new bond in the growing cluster. The expression for a kinetic barrier for new bond formation in a cluster was obtained. The shape of critical receptor clusters seems to be very important for the clustering on the cell surface. The von Neumann entropy of the graph of bonds is used to determine the influence of the cluster shape on the kinetic barrier. Numerical studies were carried out to assess the dependence of the barrier on the size of the cluster. The asymptotic expression, reflecting the conditions necessary for the formation of receptor clusters, was obtained. Several dynamic effects were found. A slight increase of the ligand mass has been shown to significantly accelerate the nucleation of receptor clusters. The possible meaning of the obtained results for medical applications is discussed.

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Qian, Panpan, Huan Zhao, Yanmin Zhu e Qiang Sun. "A Semidynamic Bidirectional Clustering Algorithm for Downlink Cell-Free Massive Distributed Antenna System". Wireless Communications and Mobile Computing 2021 (21 gennaio 2021): 1–11. http://dx.doi.org/10.1155/2021/6618126.

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Cell-free massive distributed antenna system (CF-MDAS) can further reduce the access distance between mobile stations (MSs) and remote access points (RAPs), which brings a lower propagation loss and higher multiplexing gain. However, the interference caused by the overlapping coverage areas of distributed RAPs will severely degrade the system performance in terms of the sum-rate. Since that clustering RAPs can mitigate the interference, in this paper, we investigate a novel clustering algorithm for a downlink CF-MDAS with the limited-capacity backhaul. To reduce the backhaul burden and mitigate interference effectively, a semidynamic bidirectional clustering algorithm based on the long-term channel state information (CSI) is proposed, which has a low computational complexity. Simulation results show that the proposed algorithm can efficiently achieve a higher sum-rate than that of the static clustering one, which is close to the curve obtained by dynamic clustering algorithm using the short-term CSI. Furthermore, the proposed algorithm always reveals a significant performance gain regardless of the size of the networks.

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Saltel, Frédéric, Eva Mortier, Vesa P. Hytönen, Marie-Claude Jacquier, Pascale Zimmermann, Viola Vogel, Wei Liu e Bernhard Wehrle-Haller. "New PI(4,5)P2- and membrane proximal integrin–binding motifs in the talin head control β3-integrin clustering". Journal of Cell Biology 187, n. 5 (23 novembre 2009): 715–31. http://dx.doi.org/10.1083/jcb.200908134.

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Integrin-dependent adhesion sites consist of clustered integrins that transmit mechanical forces and provide signaling required for cell survival and morphogenesis. Despite their importance, the regulation of integrin clustering by the cytoplasmic adapter protein talin (Tal) and phosphatidylinositol (PI)-4,5-biphosphate (PI(4,5)P2) lipids nor their dynamic coupling to the actin cytoskeleton is fully understood. By using a Tal-dependent integrin clustering assay in intact cells, we identified a PI(4,5)P2-binding basic ridge spanning across the F2 and F3 domains of the Tal head that regulates integrin clustering. Clustering requires a new PI(4,5)P2-binding site in F2 and is negatively regulated by autoinhibitory interactions between F3 and the Tal rod (Tal-R). The release of the Tal-R exposes a new β3-integrin–binding site in F3, enabling interaction with a membrane proximal acidic motif, which involves the formation of salt bridges between K316 and K324 with E726 and D723, respectively. This interaction shields the β-integrin tail from reassociation with its α subunit, thereby maintaining the integrin in a substrate-binding and clustering-competent form.

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Cluzel, Caroline, Frédéric Saltel, Jost Lussi, Frédérique Paulhe, Beat A. Imhof e Bernhard Wehrle-Haller. "The mechanisms and dynamics of αvβ3 integrin clustering in living cells". Journal of Cell Biology 171, n. 2 (24 ottobre 2005): 383–92. http://dx.doi.org/10.1083/jcb.200503017.

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During cell migration, the physical link between the extracellular substrate and the actin cytoskeleton mediated by receptors of the integrin family is constantly modified. We analyzed the mechanisms that regulate the clustering and incorporation of activated αvβ3 integrins into focal adhesions. Manganese (Mn2+) or mutational activation of integrins induced the formation of de novo F-actin–independent integrin clusters. These clusters recruited talin, but not other focal adhesion adapters, and overexpression of the integrin-binding head domain of talin increased clustering. Integrin clustering required immobilized ligand and was prevented by the sequestration of phosphoinositole-4,5-bisphosphate (PI(4,5)P2). Fluorescence recovery after photobleaching analysis of Mn2+-induced integrin clusters revealed increased integrin turnover compared with mature focal contacts, whereas stabilization of the open conformation of the integrin ectodomain by mutagenesis reduced integrin turnover in focal contacts. Thus, integrin clustering requires the formation of the ternary complex consisting of activated integrins, immobilized ligands, talin, and PI(4,5)P2. The dynamic remodeling of this ternary complex controls cell motility.

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Li, John Xiao He, Vivian W. Tang, Kingsley A. Boateng e William M. Brieher. "Cadherin puncta are interdigitated dynamic actin protrusions necessary for stable cadherin adhesion". Proceedings of the National Academy of Sciences 118, n. 24 (7 giugno 2021): e2023510118. http://dx.doi.org/10.1073/pnas.2023510118.

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Cadherins harness the actin cytoskeleton to build cohesive sheets of cells using paradoxically weak bonds, but the molecular mechanisms are poorly understood. In one popular model, actin organizes cadherins into large, micrometer-sized clusters known as puncta. Myosin is thought to pull on these puncta to generate strong adhesion. Here, however, we show that cadherin puncta are actually interdigitated actin microspikes generated by actin polymerization mediated by three factors (Arp2/3, EVL, and CRMP-1). The convoluted membranes in these regions give the impression of cadherin clustering by fluorescence microscopy, but the ratio of cadherin to membrane is constant. Nevertheless, these interlocking fingers of membrane are important for adhesion because perturbing their formation disrupts cell adhesion. In contrast, blocking myosin-dependent contractility does not disrupt either the interdigitated microspikes or lateral membrane adhesion. “Puncta” are zones of strong cell–cell adhesion not due to cadherin clustering but that occur because the interdigitated microspikes expand the surface area available for adhesive bond formation and increase the asperity of the cell surface to promote friction between cells.

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Ashraf, Muhammad Ikram, Mehdi Bennis, Walid Saad, Marcos Katz e Choong-Seon Hong. "Dynamic Clustering and User Association in Wireless Small-Cell Networks With Social Considerations". IEEE Transactions on Vehicular Technology 66, n. 7 (luglio 2017): 6553–68. http://dx.doi.org/10.1109/tvt.2016.2644760.

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Claus, Rainer, Philipp Sander, Dietmar Pfeifer, Lioudmila Bogatyreva, Emmanuel Bissé e Michael Lübbert. "Induction of an Erythroid but Not Megakaryocytic Expression Signature in Myeloid Cells By in Vitro 5-Aza-2'-Deoxycytidine Treatment". Blood 126, n. 23 (3 dicembre 2015): 4538. http://dx.doi.org/10.1182/blood.v126.23.4538.4538.

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Abstract Introduction: Aberrant DNA methylation is frequently found in hematologic malignancies where it is associated with altered gene expression. DNA hypomethylating agents (DNMTi), e.g. 5-aza-2'-deoxycytidine (DAC), are used for both global and gene-specific in vivo demethylation and offer a therapeutic option in myelodysplastic syndromes (MDS) and AML. DNMTi have already been utilized to upregulate suppressed fetal hemoglobin (HbF) in adult patients (pts) suffering from hemoglobinopathies. Here we systematically investigated the potential of DAC for in vitro induction of erythroid differentiation as well as HbF expression in the bipotent myeloid leukemia cell line K562 and in vivo in a clinical treatment situation in MDS pts. Methods and Results: We treated K562 cells with non-toxic concentrations of DAC (100 nM, three 24 hour pulses), hemin (50 nM) and phorbol myristate acetate (PMA, 5 nM). DAC treatment led to morphological changes indicating erythroid but not megakaryocytic differentiation. This was confirmed by benzidine staining where DAC (13% positive cells) and hemin (58%) but not PMA treated cells (0%) became positive for hemoglobin synthesis. Lack of CD41 detection by FACS analysis for DAC and hemin indicated absence of megakaryocytic differentiation. Transcriptome profiling by mRNA expression arrays (Affymetrix GeneChip® HG U133 Plus 2.0) revealed highest similarity between hemin and DAC treatment by unsupervised hierarchical clustering, followed by vehicle control and untreated cells. The transcriptome of PMA treated cells clustered most distantly to all other treatments. Both, DAC and hemin induced moderately balanced up- and downregulation of transcripts to an almost identical extent. 1414 transcripts were >2 fold upregulated and 1505 were >2 fold downregulated upon DAC treatment, whereas 1548 were up- and 2404 were downregulated in hemin treated cells, respectively. The extent of transcriptome dynamics was considerably stronger upon PMA treatment, where 4196 and 3780 transcripts were up- and downregulated, respectively. When intersecting transcriptome changes between the 3 drug treatments (Fig. 1), 368 out of 1548 (23.7%) upregulated transcripts in hemin treated cells were concordantly upregulated upon DAC treatment. The overlap of upregulated transcript was lower compared to PMA treated cells (14.9%). GO analyses of upregulated transcripts identified terms related to erythropoesis and iron metabolism among the top regulated groups of transcripts in DAC treated cells whereas terms related to megakaryocytic differentiation did not show significance. Particularly strong differences of transcripts were observed for a1-, a2-, Ag-, e- and z-globin expression upon DAC and hemin treatment, whereas b- and d-globin were expressed at low levels. These changes were not observed for PMA treated cells. Induction of a- and Ag-globin on mRNA level resulted in enrichment of a- and Ag-globin protein to 15.8% of total cellular protein amount, and consequently in HbF formation in K562 cells as assessed by reversed phase and anion exchange chromatography. HbF levels in peripheral blood were measured from 16 MDS pts, median age 74 years (range 66-78) also treated with a 3-day DAC schedule. Median HbF fraction at baseline was 0.4% (0.1-3.9%) of total hemoglobin with 6 pts (37.5%) exhibiting increased HbF levels (>1%) already before treatment. In 13/16 (81%) pts, increase of HbF with a median increment of 1.2% (range 0.3-3.7%) was observed. In 3 pts, HbF decreased over the treatment course. Median number of courses until maximum increment was 3 (2-6). HbF levels in 2 pts with AML and 1 with pancreatic cancer treated with nucleoside analogues without demethylating activity (cytosine arabinoside and gemcitabine, respectively) according to standard chemotherapy protocols served as control group and did not show comparable increments. Conclusions: We describe an erythroid differentiation program, from transcriptome level to HbF protein formation, induced by the hypomethylating agent DAC in the bipotent cell line K562. This DAC-mediated differentiation process is specific for erythropoesis but not megakaryopoesis. This is substantiated by in vivo upregulation of HbF upon DAC adminstration in MDS pts. Therefore, we propose to utilize HbF expression as potential biomarker during DAC treatment. Figure 1. Intersection of >2 fold upregulated transcripts in K562 cells upon drug treatment. Figure 1. Intersection of >2 fold upregulated transcripts in K562 cells upon drug treatment. Disclosures No relevant conflicts of interest to declare.

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Gerard, Audrey, Khan Omar e Matthew Krummel. "Visualizing the requirement for homotypic T cell synapses in enhancing CD8+ T cell differentiation. (63.11)". Journal of Immunology 186, n. 1_Supplement (1 aprile 2011): 63.11. http://dx.doi.org/10.4049/jimmunol.186.supp.63.11.

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Abstract CD8+ T cells are functionally heterogeneous and mediate their effects through a variety of mechanisms. Effective adaptive immunity relies on the capacity of lymphocytes to differentiate and yet, as a cohort to respond as a single integrated entity. But the mechanism by which the “coordinated diversification” of CD8+ T cells is regulated is not fully understood. Here, we show that homotypic clustering of nascent effector cells facilitates and coordinates their differentiation. The dynamic nature of T cell clustering upon immunization was characterized by live 2-photon imaging of explanted lymph nodes. T-T interactions are highly dynamics and are driven by LFA-1 dependent interactions. These clusters are initiated by T cell activation and occur up to two days after immunization. Functionally, reducing T cell clustering inhibits the establishment of effector and memory functions. Surprisingly, after initial activation, CD8 differentiation does not require an ongoing contact with an APC, but does require T-T interactions. T cells exchange information through synaptic structures, where increased cytokine delivery and signaling is found and is required for T cells to influence each other’s fate. Altogether, we provide evidences that a ‘collective’ CD8 response is generated through direct cell-cell communication just after their elicitation. This data may explain how tolerance is maintained and how T cell responses may rapidly amplify as additional precursors are recruited.

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Kaneko, Kunihiko. "Chaos as a Source of Complexity and Diversity in Evolution". Artificial Life 1, n. 1_2 (ottobre 1993): 163–77. http://dx.doi.org/10.1162/artl.1993.1.1_2.163.

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The relevance of chaos to evolution is discussed in the context of the origin and maintenance of diversity and complexity. Evolution to the edge of chaos is demonstrated in an imitation game. As an origin of diversity, dynamic clustering of identical chaotic elements, globally coupled each to the other, is briefly reviewed. The clustering is extended to nonlinear dynamics on hypercubic lattices, which enables us to construct a self-organizing genetic algorithm. A mechanism of maintenance of diversity, “homeochaos,” is given in an ecological system with interaction among many species. Homeochaos provides a dynamic stability sustained by high-dimensional weak chaos. A novel mechanism of cell differentiation is presented, based on dynamic clustering. Here, a new concept—“open chaos”—is proposed for the instability in a dynamical system with growing degrees of freedom. It is suggested that studies based on interacting chaotic elements can replace both top-down and bottom-up approaches.

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Ghosh, Debapriya, Madeline Nieves-Cintrón, Sendoa Tajada, Ingrid Brust-Mascher, Mary C. Horne, Johannes W. Hell, Rose E. Dixon, Luis F. Santana e Manuel F. Navedo. "Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1865, n. 9 (settembre 2018): 1341–55. http://dx.doi.org/10.1016/j.bbamcr.2018.06.013.

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Mukai, Atsushi, Tomohiro Kurisaki, Satoshi B. Sato, Toshihide Kobayashi, Gen Kondoh e Naohiro Hashimoto. "Dynamic clustering and dispersion of lipid rafts contribute to fusion competence of myogenic cells". Experimental Cell Research 315, n. 17 (ottobre 2009): 3052–63. http://dx.doi.org/10.1016/j.yexcr.2009.07.010.

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Chang, Lynne, Yaron Shav-Tal, Tatjana Trcek, Robert H. Singer e Robert D. Goldman. "Assembling an intermediate filament network by dynamic cotranslation". Journal of Cell Biology 172, n. 5 (27 febbraio 2006): 747–58. http://dx.doi.org/10.1083/jcb.200511033.

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We have been able to observe the dynamic interactions between a specific messenger RNA (mRNA) and its protein product in vivo by studying the synthesis and assembly of peripherin intermediate filaments (IFs). The results show that peripherin mRNA-containing particles (messenger ribonucleoproteins [mRNPs]) move mainly along microtubules (MT). These mRNPs are translationally silent, initiating translation when they cease moving. Many peripherin mRNPs contain multiple mRNAs, possibly amplifying the total amount of protein synthesized within these “translation factories.” This mRNA clustering is dependent on MT, regulatory sequences within the RNA and the nascent protein. Peripherin is cotranslationally assembled into insoluble, nonfilamentous particles that are precursors to the long IF that form extensive cytoskeletal networks. The results show that the motility and targeting of peripherin mRNPs, their translational control, and the assembly of an IF cytoskeletal system are linked together in a process we have termed dynamic cotranslation.

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H Roos, Wouter, Otger Campàs, Fabien Montel, Günther Woehlke, Joachim P. Spatz, Patricia Bassereau e Giovanni Cappello. "Dynamic kinesin-1 clustering on microtubules due to mutually attractive interactions". Physical Biology 5, n. 4 (24 novembre 2008): 046004. http://dx.doi.org/10.1088/1478-3975/5/4/046004.

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Yoon, Misun, Myoung-Seok Kim e Chungyong Lee. "A Dynamic Cell Clustering Algorithm for Maximization of Coordination Gain in Uplink Coordinated System". IEEE Transactions on Vehicular Technology 65, n. 3 (marzo 2016): 1752–60. http://dx.doi.org/10.1109/tvt.2015.2413899.

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da Rocha-Azevedo, Bruno, Chin-Han Ho e Frederick Grinnell. "PDGF‑stimulated dispersal of cell clusters and disruption of fibronectin matrix on three-dimensional collagen matrices requires matrix metalloproteinase-2". Molecular Biology of the Cell 26, n. 6 (15 marzo 2015): 1098–105. http://dx.doi.org/10.1091/mbc.e14-09-1396.

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Abstract (sommario):

Formation of cell clusters is a common morphogenic cell behavior observed during tissue and organ development and homeostasis, as well as during pathological disorders. Dynamic regulation of cell clustering depends on the balance between contraction of cells into clusters and migration of cells as dispersed individuals. Previously we reported that under procontractile culture conditions, fibronectin fibrillar matrix assembly by human fibroblasts functioned as a nucleation center for cell clustering on three-dimensional collagen matrices. Here we report that switching preformed cell clusters from procontractile to promigratory culture conditions results in cell dispersal out of clusters and disruption of FN matrix. Experiments using small interfering RNA silencing and pharmacological inhibition demonstrated that matrix metalloproteinase activity involving MMP-2 was necessary for fibronectin matrix disruption and dispersal of cell clusters.

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Mattila, Polly E., Chad E. Green, Ulrich Schaff, Scott I. Simon e Bruce Walcheck. "Cytoskeletal interactions regulate inducible L-selectin clustering". American Journal of Physiology-Cell Physiology 289, n. 2 (agosto 2005): C323—C332. http://dx.doi.org/10.1152/ajpcell.00603.2004.

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L-selectin (CD62L) amplifies neutrophil capture within the microvasculature at sites of inflammation. Activation by G protein-coupled stimuli or through ligation of L-selectin promotes clustering of L-selectin and serves to increase its adhesiveness, signaling, and colocalization with β2-integrins. Currently, little is known about the molecular process regulating the lateral mobility of L-selectin. On neutrophil stimulation, a progressive change takes place in the organization of its plasma membrane, resulting in membrane domains that are characteristically enriched in glycosyl phosphatidylinositol (GPI)-anchored proteins and exclude the transmembrane protein CD45. Clustering of L-selectin, facilitated by E-selectin engagement or antibody cross-linking, resulted in its colocalization with GPI-anchored CD55, but not with CD45 or CD11c. Disrupting microfilaments in neutrophils or removing a conserved cationic motif in the cytoplasmic domain of L-selectin increased its mobility and membrane domain localization in the plasma membrane. In addition, the conserved element was critical for L-selectin-dependent tethering under shear flow. Our data indicate that L-selectin’s lateral mobility is regulated by interactions with the actin cytoskeleton that in turn fortifies leukocyte tethering. We hypothesize that both membrane mobility and stabilization augment L-selectin’s effector functions and are regulated by dynamic associations with membrane domains and the actin cytoskeleton.

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Yu, Victoria Y., Dan Nguyen, Daniel O’Connor, Dan Ruan, Tania Kaprealian, Robert Chin e Ke Sheng. "Treating Glioblastoma Multiforme (GBM) with super hyperfractionated radiation therapy: Implication of temporal dose fractionation optimization including cancer stem cell dynamics". PLOS ONE 16, n. 2 (1 febbraio 2021): e0245676. http://dx.doi.org/10.1371/journal.pone.0245676.

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Abstract (sommario):

Purpose A previously developed ordinary differential equation (ODE) that models the dynamic interaction and distinct radiosensitivity between cancer stem cells (CSC) and differentiated cancer cells (DCC) was used to explain the definitive treatment failure in Glioblastoma Multiforme (GBM) for conventionally and hypo-fractionated treatments. In this study, optimization of temporal dose modulation based on the ODE equation is performed to explore the feasibility of improving GBM treatment outcome. Methods A non-convex optimization problem with the objective of minimizing the total cancer cell number while maintaining the normal tissue biological effective dose (BEDnormal) at 100 Gy, equivalent to the conventional 2 Gy × 30 dosing scheme was formulated. With specified total number of dose fractions and treatment duration, the optimization was performed using a paired simulated annealing algorithm with fractional doses delivered to the CSC and DCC compartments and time intervals between fractions as variables. The recurrence time, defined as the time point at which the total tumor cell number regrows to 2.8×109 cells, was used to evaluate optimization outcome. Optimization was performed for conventional treatment time frames equivalent to currently and historically utilized fractionation schemes, in which limited improvement in recurrence time delay was observed. The efficacy of a super hyperfractionated approach with a prolonged treatment duration of one year was therefore tested, with both fixed regular and optimized variable time intervals between dose fractions corresponding to total number of fractions equivalent to weekly, bi-weekly, and monthly deliveries (n = 53, 27, 13). Optimization corresponding to BEDnormal of 150 Gy was also obtained to evaluate the possibility in further recurrence delay with dose escalation. Results For the super hyperfractionated schedules with dose fraction number equivalent to weekly, bi-weekly, and monthly deliveries, the recurrence time points were found to be 430.5, 423.9, and 413.3 days, respectively, significantly delayed compared with the recurrence time of 250.3 days from conventional fractionation. Results show that optimal outcome was achieved by first delivering infrequent fractions followed by dense once per day fractions in the middle and end of the treatment course, with sparse and low dose treatments in the between. The dose to the CSC compartment was held relatively constant throughout while larger dose fractions to the DCC compartment were observed in the beginning and final fractions that preceded large time intervals. Dose escalation to BEDnormal of 150 Gy was shown capable of further delaying recurrence time to 452 days. Conclusion The development and utilization of a temporal dose fractionation optimization framework in the context of CSC dynamics have demonstrated that substantial delay in GBM local tumor recurrence could be achieved with a super hyperfractionated treatment approach. Preclinical and clinical studies are needed to validate the efficacy of this novel treatment delivery method.

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Sil, Parijat, Nicolas Mateos, Sangeeta Nath, Sonja Buschow, Carlo Manzo, Kenichi G. N. Suzuki, Takahiro Fujiwara, Akihiro Kusumi, Maria F. Garcia-Parajo e Satyajit Mayor. "Dynamic actin-mediated nano-scale clustering of CD44 regulates its meso-scale organization at the plasma membrane". Molecular Biology of the Cell 31, n. 7 (19 marzo 2020): 561–79. http://dx.doi.org/10.1091/mbc.e18-11-0715.

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Leong, Shwee Khuan, Jye-Chian Hsiao e Jiun-Jie Shie. "A Multiscale Molecular Dynamic Analysis Reveals the Effect of Sialylation on EGFR Clustering in a CRISPR/Cas9-Derived Model". International Journal of Molecular Sciences 23, n. 15 (6 agosto 2022): 8754. http://dx.doi.org/10.3390/ijms23158754.

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Abstract (sommario):

Bacterial and viral pathogens can modulate the glycosylation of key host proteins to facilitate pathogenesis by using various glycosidases, particularly sialidases. Epidermal growth factor receptor (EGFR) signaling is activated by ligand-induced receptor dimerization and oligomerization. Ligand binding induces conformational changes in EGFR, leading to clusters and aggregation. However, information on the relevance of EGFR clustering in the pattern of glycosylation during bacterial and viral invasion remains unclear. In this study, (1) we established CRISPR/Cas9-mediated GFP knock-in (EGFP-KI) HeLa cells expressing fluorescently tagged EGFR at close to endogenous levels to study EGF-induced EGFR clustering and molecular dynamics; (2) We studied the effect of sialylation on EGF-induced EGFR clustering and localization in live cells using a high content analysis platform and raster image correlation spectroscopy (RICS) coupled with a number and brightness (N&B) analysis; (3) Our data reveal that the removal of cell surface sialic acids by sialidase treatment significantly decreases EGF receptor clustering with reduced fluorescence intensity, number, and area of EGFR-GFP clusters per cell upon EGF stimulation. Sialylation appears to mediate EGF-induced EGFR clustering as demonstrated by the change of EGFR-GFP clusters in the diffusion coefficient and molecular brightness, providing new insights into the role of sialylation in EGF-induced EGFR activation; and (4) We envision that the combination of CRISPR/Cas9-mediated fluorescent tagging of endogenous proteins and fluorescence imaging techniques can be the method of choice for studying the molecular dynamics and interactions of proteins in live cells.

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de la Fuente, Hortensia, María Mittelbrunn, Lorena Sánchez-Martín, Miguel Vicente-Manzanares, Amalia Lamana, Ruggero Pardi, Carlos Cabañas e Francisco Sánchez-Madrid. "Synaptic Clusters of MHC Class II Molecules Induced on DCs by Adhesion Molecule–mediated Initial T-Cell Scanning". Molecular Biology of the Cell 16, n. 7 (luglio 2005): 3314–22. http://dx.doi.org/10.1091/mbc.e05-01-0005.

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Abstract (sommario):

Initial adhesive contacts between T lymphocytes and dendritic cells (DCs) facilitate recognition of peptide-MHC complexes by the TCR. In this report, we studied the dynamic behavior of adhesion and Ag receptors on DCs during initial contacts with T-cells. Adhesion molecules LFA-1- and ICAM-1,3-GFP as well as MHC class II-GFP molecules were very rapidly concentrated at the DC contact area. Binding of ICAM-3, and ICAM-1 to a lesser extent, to LFA-1 expressed by mature but not immature DC, induced MHC-II clustering into the immune synapse. Also, ICAM-3 binding to DC induced the activation of the Vav1-Rac1 axis, a regulatory pathway involved in actin cytoskeleton reorganization, which was essential for MHC-II clustering on DCs. Our results support a model in which ICAM-mediated MHC-II clustering on DC constitutes a priming mechanism to enhance antigen presentation to T-cells.

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Sung, K. L., L. A. Sung, M. Crimmins, S. J. Burakoff e S. Chien. "Dynamic changes in viscoelastic properties in cytotoxic T-lymphocyte-mediated killing". Journal of Cell Science 91, n. 2 (1 ottobre 1988): 179–89. http://dx.doi.org/10.1242/jcs.91.2.179.

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The biophysical properties of cytotoxic T lymphocytes during the killing of their target cells was investigated by using a human cytotoxic T lymphocyte clone, F1, and the target cell, JY, for which it is specific. In single cytotoxic cell/target cell pairs after their conjugation there are changes in the viscoelastic properties of the target cell in association with the lethal hit delivery and post-binding cytolytic steps. On the basis of these changes in the target cell, the complex cytolytic event can be divided into stages: the viscoelastic coefficients exhibited an initial increase followed by a return to resting values; thereafter these coefficients decreased below control and then rose again prior to lysis. The eventual killing of the target cell involves bubbling and swelling of the nucleus, clustering of granules, damage to the cytoplasmic membrane, cell swelling, and lysis. The viscoelastic changes involved in target cell death suggest the loss of integrity of its cytoskeletal apparatus.

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Gava, Fabien, Julie Pignolet, Sébastien Déjean, Odile Mondésert, Renaud Morin, Joseph Agossa, Bernard Ducommun e Valérie Lobjois. "Quantitative Analysis of Cell Aggregation Dynamics Identifies HDAC Inhibitors as Potential Regulators of Cancer Cell Clustering". Cancers 13, n. 22 (21 novembre 2021): 5840. http://dx.doi.org/10.3390/cancers13225840.

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Abstract (sommario):

Characterization of the molecular mechanisms involved in tumor cell clustering could open the way to new therapeutic strategies. Towards this aim, we used an in vitro quantitative procedure to monitor the anchorage-independent cell aggregation kinetics in a panel of 25 cancer cell lines. The analysis of the relationship between selected aggregation dynamic parameters and the gene expression data for these cell lines from the CCLE database allowed identifying genes with expression significantly associated with aggregation parameter variations. Comparison of these transcripts with the perturbagen signatures from the Connectivity Map resource highlighted that they were strongly correlated with the transcriptional signature of most histone deacetylase (HDAC) inhibitors. Experimental evaluation of two HDAC inhibitors (SAHA and ISOX) showed that they inhibited the initial step of in vitro tumor cell aggregation. This validates our findings and reinforces the potential interest of HDCA inhibitors to prevent metastasis spreading.

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Milo, Idan, Anita Sapoznikov, Vyacheslav Kalchenko, Orna Tal, Rita Krauthgamer, Nico van Rooijen, Diana Dudziak, Steffen Jung e Guy Shakhar. "Dynamic imaging reveals promiscuous crosspresentation of blood-borne antigens to naïve CD8+ T cells in the bone marrow". Blood 122, n. 2 (11 luglio 2013): 193–208. http://dx.doi.org/10.1182/blood-2012-01-401265.

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Abstract (sommario):

Key Points Soluble blood-borne antigens are crosspresented in the BM, triggering T-cell arrest, clustering, and in situ proliferation. In the BM, not only DCs but also other mononuclear phagocytes participate in crosspresentation.

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