The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.
Public transportation is becoming increasingly important in regions where the residential population is decreasing. In Japan, many regional transportation systems are experiencing financial challenges. It is difficult for fixed-route transportation systems to operate at a surplus when serving only local resident users. We consider one of the problems of these regional public transport systems to be the lack of information on the Internet about regional public transportation routes. For people who are unfamiliar with the region, such as inbound tourists, there is no easy way to conduct a route search. In this paper, we describe our efforts to build a fundamental database of the regional public transportation provided by municipalities and to publish this data for those conducting route searches on the Internet. Specifically, we converted fundamental data regarding regional public transportation to the feed of the General Transit Feed Specification-Japan (GTFS-JP), which is based on the Google GTFS, as formulated by the Ministry of Land in Japan. Then we encouraged municipalities to publish these transit data to enable route searches on Google Maps and other domestic-content providers.
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