Forkhead box, class O (FOXO) family proteins are widely expressed and highly conserved transcriptional regulators that modulate cellular fuel metabolism, stress resistance and cell death. FOXO target genes include genes encoding antioxidant proteins, thus likely contributing to the key role FOXOs play in the cellular response to oxidative stress and supporting the cellular strategies of antioxidant defense, that is, prevention (of the formation of reactive oxygen species), interception (of reactive species prior to their reaction with cellular components), repair (of damaged biomolecules), and adaptation (i.e., the stimulation of signaling pathways allowing for the expression of protective proteins). FOXOs themselves are regulated by redox processes at several levels, including expression of FOXO genes and enzymatic as well as nonenzymatic posttranslational modifications of FOXO proteins. The latter include modifications of FOXO cysteine residues. Here, an overview is provided on (i) the contribution of FOXO target genes to cellular antioxidative strategies, and (ii) on the impact of thiol homeostasis and thiol modification on FOXO activity.
In this paper, an efficient approach to data validation of geographical interlocking systems (IXLs) is presented. It is explained how configuration rules for IXLs can be specified by temporal logic formulas interpreted on Kripke structure representations of the IXL configuration. Violations of configuration rules can be specified using formulas from a well-defined subset of LTL. By decomposing the complete configuration model into sub-models corresponding to routes through the model, the LTL model checking problem can be transformed into a CTL checking problem for which highly efficient algorithms exist. Specialised rule violation queries that are hard to express in LTL can be simplified and checked faster by performing sub-model transformations adding auxiliary variables to the states of the underlying Kripke structures. Further performance enhancements are achieved by checking each sub-model concurrently. The approach presented here has been implemented in a model checking tool which is applied by Siemens for data validation of geographical IXLs.
In this paper, it is shown how a complete input equivalence class testing strategy developed by the second author can be effectively used for infinite-state model checking of system models with infinite input domains but finitely many internal state values and finite output domains. This class of systems occurs frequently in the safety-critical domain, where controllers may input conceptually infinite analogue data, but make a finite number of control decisions based on inputs and current internal state. A variant of Kripke Structures is well-suited to provide a behavioural model for this system class. It is shown how the known construction of specific input equivalence classes can be used to abstract the infinite input domain of the reference model into finitely many classes. Then quick checks can be made on the implementation model showing that the implementation is not I/O-equivalent to the reference model if its abstraction to observable minimal finite state machines has a different number of states or a different input partitioning as the reference model. Only if these properties are consistent with the reference model, a detailed equivalence check between the abstracted models needs to be performed. The complete test suites obtained as a by-product of the checking procedure can be used to establish counter examples showing the non-conformity between implementation model and reference model. Using various sample models, it is shown that this approach outperforms model checkers that do not possess this equivalence class generation capability.
In this paper, an efficient approach to data validation of distributed geographical interlocking systems (IXLs) is presented. In the distributed IXL paradigm, track elements are controlled by local computers communicating with other control components over local and wide area networks. The overall control logic is distributed over these track-side computers and remote server computers that may even reside in one or more cloud server farms. Redundancy is introduced to ensure fail-safe behaviour, fault-tolerance, and to increase the availability of the overall system. To cope with the configuration-related complexity of such distributed IXLs, the software is designed according to the digital twin paradigm: physical track elements are associated with software objects implementing supervision and control for the element. The objects communicate with each other and with high-level IXL control components in the cloud over logical channels realised by distributed communication mechanisms. The objective of this article is to explain how configuration rules for this type of IXLs can be specified by temporal logic formulae interpreted on Kripke Structure representations of the IXL configuration. Violations of configuration rules can be specified using formulae from a well-defined subset of LTL. By decomposing the complete configuration model into sub-models corresponding to routes through the model, the LTL model checking problem can be transformed into a CTL checking problem for which highly efficient algorithms exist. Specialised rule violation queries that are hard to express in LTL can be simplified and checked faster by performing sub-model transformations adding auxiliary variables to the states of the underlying Kripke Structures. Further performance enhancements are achieved by checking each sub-model concurrently. The approach presented here has been implemented in a model checking tool which is applied by Siemens Mobility for data validation of geographical IXLs.
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