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Tumor is a complex and aggressive type of disease that poses significant health challenges. Understanding the cellular mechanisms underlying its progression is crucial for developing effective treatments. In this study, we develop a novel mathematical framework to investigate the role of cellular plasticity and heterogeneity in tumor progression. By leveraging temporal single-cell data, we propose a reaction–convection–diffusion model that effectively captures the spatiotemporal dynamics of tumor cells and macrophages within the tumor microenvironment. Through theoretical analysis, we obtain the estimate of the pulse wave speed and analyze the stability of the homogeneous steady state solutions. Notably, we employe the AddModuleScore function to quantify cellular plasticity. One of the highlights of our approach is the introduction of pulse wave speed as a quantitative measure to precisely gauge the rate of cell phenotype transitions, as well as the novel implementation of the high-plasticity cell state/low-plasticity cell state ratio as an indicator of tumor malignancy. Furthermore, the bifurcation analysis reveals the complex dynamics of tumor cell populations. Our extensive analysis demonstrates that an increased rate of phenotype transition is associated with heightened malignancy, attributable to the tumor’s ability to explore a wider phenotypic space. The study also investigates how the proliferation rate and the death rate of tumor cells, phenotypic convection velocity, and the midpoint of the phenotype transition stage affect the speed of tumor cell phenotype transitions and the progression to adenocarcinoma. These insights and quantitative measures can help guide the development of targeted therapeutic strategies to regulate cellular plasticity and control tumor progression effectively. [ABSTRACT FROM AUTHOR]

The assembly of the HIV-1 immature capsid (HIC) is an essential step in the virus life cycle. In vivo, the HIC is composed of ∼ 420 hexameric building blocks, and it takes 5–6 min to complete the assembly process. The involvement of numerous building blocks and the rapid timecourse makes it difficult to understand the HIC assembly process. In this work, we study HIC assembly in vivo by using differential equations. We first obtain a full model with 420 differential equations. Then, we reduce six addition reactions for separate building blocks to a single complex reaction. This strategy reduces the full model to 70 equations. Subsequently, the theoretical analysis of the reduced model shows that it might not be an effective way to decrease the HIC concentration at the equilibrium state by decreasing the microscopic on-rate constants. Based on experimental data, we estimate that the nucleating structure is much smaller than the HIC. We also estimate that the microscopic on-rate constant for nucleation reactions is far less than that for elongation reactions. The parametric collinearity investigation testifies the reliability of these two characteristics, which might explain why free building blocks do not readily polymerize into higher-order polymers until their concentration reaches a threshold value. These results can provide further insight into the assembly mechanisms of the HIC in vivo. [ABSTRACT FROM AUTHOR]

Recently, controllability of complex networks has attracted enormous attention in various fields of science and engineering. How to optimize structural controllability has also become a significant issue. Previous studies have shown that an appropriate directional assignment can improve structural controllability; however, the evolution of the structural controllability of complex networks under attacks and cascading has always been ignored. To address this problem, this study proposes a new edge orientation method (NEOM) based on residual degree that changes the link direction while conserving topology and directionality. By comparing the results with those of previous methods in two random graph models and several realistic networks, our proposed approach is demonstrated to be an effective and competitive method for improving the structural controllability of complex networks. Moreover, numerical simulations show that our method is near-optimal in optimizing structural controllability. Strikingly, compared to the original network, our method maintains the structural controllability of the network under attacks and cascading, indicating that the NEOM can also enhance the robustness of controllability of networks. These results alter the view of the nature of controllability in complex networks, change the understanding of structural controllability and affect the design of network models to control such networks. [ABSTRACT FROM AUTHOR]

Differential evolution (DE) has been used to solve real-parameter optimization problems with nonlinear and multimodal functions for more than a decade of years. However, it is pointed out that this classical DE harbors restricted efficiency and limited local search ability. Inspired by that gradient-based algorithms have powerful local search ability, we propose a new algorithm, which is diversity-maintained DE based on gradient local search (namely, DMGBDE), by incorporating approximate gradient-based algorithms into the DE search while maintaining the diversity of the population. The primary novelties of the proposed DMGBDE are the following: (1) the gradient-based algorithm is embedded into DE in a different manner and (2) a diversity-maintained mutation is introduced to slow down the learning procedure from the searched best individual. We conduct numerical experiments with a number of benchmark problems to measure the performance of the proposed DMGBDE. Simulation results show that the proposed DMGBDE outperforms classical DE and variant without gradient local search or diversity-based mutation. Moreover, comparison with some other recently reported approaches indicates that our proposed DMGBDE is rather competitive. [ABSTRACT FROM AUTHOR]

In this paper, a new dynamical evolutionary algorithm (DEA) is presented based on the theory of statistical mechanics. The novelty of this kind of dynamical evolutionary algorithm is that all individuals in a population (called particles in a dynamical system) are running and searching with their population evolving driven by a new selecting mechanism. This mechanism simulates the principle of molecular dynamics, which is easy to design and implement. A basic theoretical analysis for the dynamical evolutionary algorithm is given and as a consequence two stopping criteria of the algorithm are derived from the principle of energy minimization and the law of entropy increasing. In order to verify the effectiveness of the scheme, DEA is applied to solving some typical numerical function minimization problems which are poorly solved by traditional evolutionary algorithms. The experimental results show that DEA is fast and reliable. [ABSTRACT FROM AUTHOR]

The early diagnosis and investigation of the pathogenic mechanisms of complex diseases are the most challenging problems in the fields of biology and medicine. Network-based systems biology is an important technique for the study of complex diseases. The present study constructed dynamic protein-protein interaction (PPI) networks to identify dynamical network biomarkers (DNBs) and analyze the underlying mechanisms of complex diseases from a systems level. We developed a model-based framework for the construction of a series of time-sequenced networks by integrating high-throughput gene expression data into PPI data. By combining the dynamic networks and molecular modules, we identified significant DNBs for four complex diseases, including influenza caused by either H3N2 or H1N1, acute lung injury and type 2 diabetes mellitus, which can serve as warning signals for disease deterioration. Function and pathway analyses revealed that the identified DNBs were significantly enriched during key events in early disease development. Correlation and information flow analyses revealed that DNBs effectively discriminated between different disease processes and that dysfunctional regulation and disproportional information flow may contribute to the increased disease severity. This study provides a general paradigm for revealing the deterioration mechanisms of complex diseases and offers new insights into their early diagnoses. [ABSTRACT FROM AUTHOR]