Comparison between 1-D and grey-box models of a SOFC

Solid Oxide Fuel Cells (SOFCs) have shown unique performance in terms of greater electrical efficiency and thermochemical integrity with the power systems compared to gas turbines and internal combustion engines. Nonetheless, simple and reliable models still must be defined. In this paper, a comparison between a grey-box model and a 1-D model of a SOFC is performed to understand the impact of the heat transfer inside the cell on the internal temperature distribution of the solid electrolyte. Hence, a significant internal temperature peak of the solid electrolyte is observed for a known difference between anode and cathode inlet temperatures. Indeed, it highlights the difference between the 1-D model and the grey-box model regarding the thermal conditioning of the SOFC. Therefore, the results of this study can be used to investigate the reliability of the thermal results of box models in system-level simulations

Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway

The Notch-Delta signaling pathway mediates cell differentiation implicated in many regulatory processes including spatiotemporal patterning in tissues by promoting alternate cell fates between neighboring cells. At the multicellular level, this "lateral inhibition” principle leads to checkerboard patterns with alternation of Sender and Receiver cells. While it is well known that stochasticity modulates cell fate specification, little is known about how stochastic fluctuations at the cellular level propagate during multicell pattern formation. Here, we model stochastic fluctuations in the Notch-Delta pathway in the presence of two different noise types–shot and white–for a multicell system. Our results show that intermediate fluctuations reduce disorder and guide the multicell lattice toward checkerboard-like patterns. By further analyzing cell fate transition events, we demonstrate that intermediate noise amplitudes provide enough perturbation to facilitate “proofreading” of disordered patterns and cause cells to switch to the correct ordered state (Sender surrounded by Receivers, and vice versa). Conversely, high noise can override environmental signals coming from neighboring cells and lead to switching between ordered and disordered patterns. Therefore, in analogy with spin glass systems, intermediate noise levels allow the multicell Notch system to escape frustrated patterns and relax towards the lower energy checkerboard pattern while at large noise levels the system is unable to find this ordered base of attraction

Quantifying cancer epithelial-mesenchymal plasticity and its association with stemness and immune response

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.Comment: 50 pages, 6 figure

Theoretical and computational tools to model multistable gene regulatory networks

The last decade has witnessed a surge of theoretical and computational models to describe the dynamics of complex gene regulatory networks, and how these interactions can give rise to multistable and heterogeneous cell populations. As the use of theoretical modeling to describe genetic and biochemical circuits becomes more widespread, theoreticians with mathematics and physics backgrounds routinely apply concepts from statistical physics, non-linear dynamics, and network theory to biological systems. This review aims at providing a clear overview of the most important methodologies applied in the field while highlighting current and future challenges, and includes hands-on tutorials to solve and simulate some of the archetypical biological system models used in the field. Furthermore, we provide concrete examples from the existing literature for theoreticians that wish to explore this fast-developing field. Whenever possible, we highlight the similarities and differences between biochemical and regulatory networks and classical systems typically studied in non-equilibrium statistical and quantum mechanics.Comment: 73 pages, 12 figure

Editorial: Epithelial to Mesenchymal Plasticity in Colorectal Cancer

Editorial on the Research Topic Epithelial to Mesenchymal Plasticity in Colorectal Cance

New antiproliferative agents derived from tricyclic 3,4-dihydrobenzo[4,5]imidazo[1,2-a][1,3,5]triazine scaffold: synthesis and pharmacological effects

A series of novel 3,4‐dihydrobenzo[4,5]imidazo[1,2‐a][1,3,5]triazine (BIT) derivatives were designed and synthesized. In vitro antiproliferative activity was detected toward two human colorectal adenocarcinoma cell lines (CaCo‐2 and HT‐29) and one human dermal microvascular endothelial cell line (HMVEC‐ d). The most active compounds, namely 2‐4 and 8, were further investigated to clarify the mechanism behind their biological activity. Through immuno fluorescence assay, we identified the target of these molecules to be the microtubule cytoskeleton with subsequent formation of dense microtubule accumulation, particularly at the periphery of the cancer cells, as observed in paclitaxel‐treated cells. Overall, these results highlight BIT derivatives as robust and feasible candidates deserving to be further developed in the search for novel potent antiproliferative microtubule‐targeting agents