Dynamics of a network mediated by IL-36 and involved in the pathogenesis of psoriasis.

The pathogenesis of the inflammatory, chronic, and common skin disease psoriasis involves immune cells, skin cells (keratinocytes), and the cytokines they secrete. Hyperproliferation and abnormal differentiation of keratinocytes are hallmarks of the disease. The roles of cytokines such as TNFα, IL-15, IL-17, and IL-23 in psoriasis have been studied through mathematical/computational models as well as experiments. However, the role of proinflammatory cytokine IL-36 in the onset and progression of psoriasis is still elusive. To explore the role of IL-36, we construct a network embodying indirect cell-cell interactions of a few immune and skin cells mediated by IL-36 based on existing knowledge. We also develop a mathematical model for the network and perform a global sensitivity analysis. Our results suggest that the model is most sensitive to a parameter that represents the level of cytokine IL-36. In addition, a steady-state analysis of the model suggests that an increase in the level of IL-36 could lead to the hyperproliferation of keratinocytes and, thus, psoriasis. Our analysis also highlights that the plaque formation and progression of psoriasis could occur through either a gradual or a switch-like increase in the keratinocyte population. We propose that the switch-like increase would be due to a bistable behavior of the network toward either a psoriatic or healthy state and could be used as a novel treatment strategy.

Role of subnetworks mediated by [Formula: see text], IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis.

Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving [Formula: see text], IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of [Formula: see text], IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of [Formula: see text] would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.

Consensus-Based Odor Source Localization by Multiagent Systems Under Resource Constraints.

With advancements in mobile robot olfaction, networked multiagent systems (MASs) are used in odor source localization (OSL). These MASs are often equipped with small microprocessors that have limited computing capabilities, and they usually operate in a bandwidth and energy-constrained environment. The exigent need for a faster localizing algorithm under communication and computational resource constraints invites many design challenges. In this paper, we have designed a two-level hierarchical cooperative control strategy for heterogeneous nonlinear MASs for OSL. The agents are forced toward consensus expeditiously once the information on the whereabouts of the source is attained. The synthesis of the controller occurs in a hierarchical manner-obtaining a group decision, followed by resource-efficient robust control. Odor concentration and wind information have been used in a group decision-making layer to predict a probable location of the source as a tracking reference. This reference is then fed to the control layer that is synthesized using event-triggered sliding-mode control (SMC). The advantage of using event-triggered control scheduling in conjunction with the SMC is rooted in retaining the robustness of the SMC while lowering the resource utilization burden. Numerical simulations confirm the efficiency of the scheme put forth.