Adaptive Fault Tolerance and Graceful Degradation Under Dynamic Hard Real-time Scheduling

Static redundancy allocation is inappropriate in hard realtime systems that operate in variable and dynamic environments, (e.g., radar tracking, avionics). Adaptive Fault Tolerance (AFT) can assure adequate reliability of critical modules, under temporal and resources constraints, by allocating just as much redundancy to less critical modules as can be afforded, thus gracefully reducing their resource requirement. In this paper, we propose a mechanism for supporting adaptive fault tolerance in a real-time system. Adaptation is achieved by choosing a suitable redundancy strategy for a dynamically arriving computation to assure required reliability and to maximize the potential for fault tolerance while ensuring that deadlines are met. The proposed approach is evaluated using a real-life workload simulating radar tracking software in AWACS early warning aircraft. The results demonstrate that our technique outperforms static fault tolerance strategies in terms of tasks meeting their timing constraints. Further, we show that the gain in this timing-centric performance metric does not reduce the fault tolerance of the executing tasks below a predefined minimum level. Overall, the evaluation indicates that the proposed ideas result in a system that dynamically provides QOS guarantees along the fault-tolerance dimension

Transcriptional Reversion of Cardiac Myocyte Fate During Mammalian Cardiac Regeneration

Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine whether myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte (CM) regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo CM differentiation, in vitro CM explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of CM differentiation processes, including reactivation of latent developmental programs similar to those observed during destabilization of a mature CM phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13, which induced CM cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of interleukin 13 signaling in CMs. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Keywords: cardiac myocyte; gene expression; growth factors/cytokines; myogenesis regenerationNational Institutes of Health (U.S.) (Grant F32HL104913)National Institutes of Health (U.S.) (Grant K99HL122514)National Institutes of Health (U.S.) (Grant U01HL098179)Natioanal Science Foundation (U.S.) (Grant CBET-0939511

Transcriptional reversion of cardiac myocyte fate during mammalian cardiac regeneration

Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine whether myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte (CM) regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo CM differentiation, in vitro CM explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of CM differentiation processes, including reactivation of latent developmental programs similar to those observed during destabilization of a mature CM phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13, which induced CM cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of interleukin 13 signaling in CMs. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration.Stem Cell and Regenerative Biolog