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See detailOptimal Priority Assignment for Real-Time Systems: A Coevolution-Based Approach
Lee, Jaekwon UL; Shin, Seung Yeob UL; Nejati, Shiva et al

in Emperical Software Engineering (in press)

In real-time systems, priorities assigned to real-time tasks determine the order of task executions, by relying on an underlying task scheduling policy. Assigning optimal priority values to tasks is ... [more ▼]

In real-time systems, priorities assigned to real-time tasks determine the order of task executions, by relying on an underlying task scheduling policy. Assigning optimal priority values to tasks is critical to allow the tasks to complete their executions while maximizing safety margins from their specified deadlines. This enables real-time systems to tolerate unexpected overheads in task executions and still meet their deadlines. In practice, priority assignments result from an interactive process between the development and testing teams. In this article, we propose an automated method that aims to identify the best possible priority assignments in real-time systems, accounting for multiple objectives regarding safety margins and engineering constraints. Our approach is based on a multi-objective, competitive coevolutionary algorithm mimicking the interactive priority assignment process between the development and testing teams. We evaluate our approach by applying it to six industrial systems from different domains and several synthetic systems. The results indicate that our approach significantly outperforms both our baselines, i.e., random search and sequential search, and solutions defined by practitioners. Our approach scales to complex industrial systems as an offline analysis method that attempts to find near-optimal solutions within acceptable time, i.e., less than 16 hours. [less ▲]

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See detailTetrahydrobenzimidazole TMQ0153 triggers apoptosis, autophagy and necroptosis crosstalk in chronic myeloid leukemia
Song, S.; Lee, J.-Y.; Ermolenko, L. et al

in Cell Death and Disease (2020), 11(2),

By comparing imatinib-sensitive and -resistant chronic myeloid leukemia (CML) cell models, we investigated the molecular mechanisms by which tetrahydrobenzimidazole derivative TMQ0153 triggered caspase ... [more ▼]

By comparing imatinib-sensitive and -resistant chronic myeloid leukemia (CML) cell models, we investigated the molecular mechanisms by which tetrahydrobenzimidazole derivative TMQ0153 triggered caspase-dependent apoptosis at low concentrations accompanied by loss of mitochondrial membrane potential (MMP) and increase of cytosolic free Ca2+ levels. Interestingly, at higher concentrations, TMQ0153 induced necroptotic cell death with accumulation of ROS, both preventable by N-acetyl-L-cysteine (NAC) pretreatment. At necroptosis-inducing concentrations, we observed increased ROS and decreased ATP and GSH levels, concomitant with protective autophagy induction. Inhibitors such as bafilomycin A1 (baf-A1) and siRNA against beclin 1 abrogated autophagy, sensitized CML cells against TMQ0153 and enhanced necroptotic cell death. Importantly, TMQ153-induced necrosis led to cell surface exposure of calreticulin (CRT) and ERp57 as well as the release of extracellular ATP and high mobility group box (HMGB1) demonstrating the capacity of this compound to release immunogenic cell death (ICD) markers. We validated the anti-cancer potential of TMQ0153 by in vivo inhibition of K562 microtumor formation in zebrafish. Taken together, our findings provide evidence that cellular stress and redox modulation by TMQ0153 concentration-dependently leads to different cell death modalities including controlled necrosis in CML cell models. © 2020, The Author(s). [less ▲]

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