A recipe for myositis : nuclear factor κB and nuclear factor of activated T-cells transcription factor pathways spiced up by cytokines

Nuclear factor κB (NF-κB) is a well-known pro-inflammatory transcription factor that regulates the expression of the tissue’s immune-active components, which include cytokines, chemokines and adhesion molecules. In addition, the versatile nuclear factor of activated T-cells (NFAT) family of transcription factors plays a crucial role in the development and function of the immune system, integrating calcium signaling with other signaling pathways. NF-κB and NFAT share many structural and functional characteristics and likely regulate gene expression through shared enhancer elements. This review describes recent research data that has led to new insights into the involvement of NFκB- and NFAT-mediated pathways in the different idiopathic inflammatory myopathies. The general activation of NF-κB p65 in blood vessel endothelium, seems to flag down inflammatory cells that subsequently accumulate mostly at perimysial sites in dermatomyositis. The joint activation of p65 and NFAT5 in myofibers specifically at perifascicular areas reflects the characteristic tissue damage pattern observed in that particular subgroup of patients. In immune cells actively invading nonnecrotic muscle fibers in polymyositis and sporadic inclusion body myositis on the other hand, p65 activation is an important aspect of their cytotoxic and chemoattactant properties. In addition, both transcription factor families are generally upregulated in regenerating muscle fibers as components of the differentiation process. It can be concluded that the two transcription factor families function in close relationship with each other, representing two-edged swords for muscle disease: on the one hand promoting cell growth and regeneration, while on the other hand actively participating in inflammatory cell damage. In this respect, cytokines function as important go-betweens at the crossroads of the pathways. Beyond NF-κB and NFAT, many fascinating winding roads relevant to inflammatory myopathy disease management still lie ready for the exploring

Modelling and controlling traffic behaviour with continuous Petri nets

Traffic systems are discrete systems that can be heavily populated. One way of overcoming the state explosion problem inherent to heavily populated discrete systems is to relax the discrete model. Continuous Petri nets (PN) represent a relaxation of the original discrete Petri nets that leads to a compositional formalism to model traffic behaviour. This paper introduces some new features of continuous Petri nets that are useful to obtain realistic but compact models for traffic systems. Combining these continuous PN models with discrete PN models of traffic lights leads to a hybrid Petri net model that is appropriate for predicting traffic behaviour, and for designing trac light controllers that minimize the total delay of the vehicles in the system

On Fault Diagnosis of random Free-choice Petri Nets

This paper presents an on-line diagnosis algorithm for Petri nets where a priori probabilistic knowledge about the plant operation is available. We follow the method developed by Benveniste, Fabre, and Haar to assign probabilities to configurations in a net unfolding thus avoiding the need for randomizing all concurrent interleavings of transitions. We consider different settings of the diagnosis problem, including estimating the likelihood that a fault may have happened prior to the most recent observed event, the likelihood that a fault will have happened prior to the next observed event. A novel problem formulation treated in this paper considers deterministic diagnosis of faults that occurred prior to the most recent observed event, and simultaneous calculation of the likelihood that a fault will occur prior to the next observed event

Distributed voltage control in electrical power systems

Voltage instability stems from the attempt of load dynamics to restore power consumption beyond the capability of the combined transmission and generation system. Discrete event controllers such as load tap changing transformers (LTCs), electronically controlled HVDC lines and switched capacitor banks can locally maintain the voltage but following a major disturbance that causes a strong decrease in the voltages, there are some interaction between LTCs action and up to now there has been relatively little attention paid to coordination between important components in voltage stability using message exchange between them and applying distributed control and taking discrete events into account. So, this study aims at voltage stability enhancement by using coordinated control of the discrete event controllers by using message exchange between the different local control agents. Various approaches for coordinating local controllers (e.g. distributed model predictive controllers) will be investigated. The influence of the discrete event driven local voltage controllers on remote locations of the network has to be investigated in a hybrid systems model framework

Scanning for therapeutic targets within the cytokine network of idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of chronic disorders that include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). They represent distinct pathological entities that, most often, share predominant inflammation in muscle tissue. Many of the immunopathogenic processes behind the IIM remain poorly understood, but the crucial role of cytokines as essential regulators of the intramuscular build-up of inflammation is undisputed. This review describes the extensive cytokine network within IIM muscle, characterized by strong expression of Tumor Necrosis Factors (TNF, LT, BAFF), Interferons (IFN//), Interleukins (IL-1/6/12/15/18/23) and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21). Current therapeutic strategies and the exploration of potential disease modifying agents based on manipulation of the cytokine network are provided. Reported responses to anti-TNF treatment in IIM are conflicting and new onset DM/PM has been described after administration of anti-TNF agents to treat other diseases, pointing to the complex effects of TNF neutralization. Treatment with anti-IFN has been shown to suppress the IFN type 1 gene signature in DM/PM patients and improve muscle strength. Beneficial effects of anti-IL-1 and anti-IL-6 therapy have also been reported. Cytokine profiling in IIM aids the development of therapeutic strategies and provides approaches to subtype patients for treatment outcome prediction

A platoon based model for urban traffic networks: identification, modeling and distributed control

Urban traffic control poses a challenging problem in terms of coordinating the different traffic lights that can be used in order to influence the traffic flow. The goal of this approach is to identify and to develop hybrid system models of controlled and uncontrolled intersections and links in urban traffic networks based on formation of platoons. The other purpose is to develop a feedback control algorithm that optimizes the signal timing plan based on the strategy of platoons formation estimated via the vehicle re-identification technology

Distributed control of urban traffic networks using hybrid models

Urban traffic control poses a challenging problem in terms of coordinating the different traffic lights that can be used in order to influence the traffic flow. Model based control requires hybrid systems models consisting of interacting fluid flow Petri net models for controlled and uncontrolled intersections, and cell transmission models for links connecting the intersections. This paper proposes a simulation based distributed model predictive control algorithm for solving this problem