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Triple modular redundancy (TMR) fault tolerance mechanism can provide almost perfect fault-masking, which has the great potential to enhance the reliability of real-time systems. However, multiple copies of a task are executed concurrently, which will lead to a sharp increase in system energy consumption. In this work, the problem of parallel applications using TMR on heterogeneous multi-core platforms to minimize energy consumption is studied. First, the heterogeneous earliest finish time algorithm is improved, and then according to the given application's deadline constraints and reliability requirements, an algorithm to extend the execution time of the copies is designed. Secondly, based on the properties of TMR, an algorithm for minimizing the execution overhead of the third copy (MEOTC) is designed. Finally, considering the actual situation of task execution, an online energy management (OEM) method is proposed. The proposed algorithms were compared with the state-of-the-art AFTSA algorithm, and the results show significant differences in energy consumption. Specifically, for light fault detection, the energy consumption of the MEOTC and OEM algorithms was found to be 80% and 72% respectively, compared with AFTSA. For heavy fault detection, the energy consumption of MEOTC and OEM was measured at 61% and 55% respectively, compared with AFTSA. • A TMR fault tolerance mechanism is applied to heterogeneous multi-core real-time systems. • Four energy-efficient algorithms are designed with deadline and reliability constraints. • The proposed algorithms outperform existing task replication approach in most cases. [ABSTRACT FROM AUTHOR]

Abstract The embedded systems generally require to be low-powered and highly reliable. In order to achieve the low-power design goal, dynamic voltage frequency scaling (DVFS) technique has been widely employed in various embedded application scenarios. However, DVFS reduces execution frequency, which increases transient faults of the processor dramatically. As a result, the reliability of the application will be severely reduced. In this paper, we aim at minimizing energy consumption with reliability goal for parallel application on heterogeneous embedded systems. Since the reliability of the application is the product of the reliability of all the tasks that belong to the application, the reliability goal of the application is transformed into the reliability goal of each task. Considering that some systems may not support DVFS techniques, two methods are proposed to transform the reliability goal of the application into each task for non-DVFS and DVFS, respectively. Based on the reliability goal transformation methods, two energy-efficient scheduling algorithms with the reliability goal are designed. Experiments with real parallel applications demonstrate that the proposed algorithms have significant improvements in energy efficiency compared with the state-of-the-art algorithms. Highlights • The reliability goal of the application is transformed to that of each task. • The reliability goal transformation methods for non-DVFS and DVFS are both proposed. • Two energy-efficient scheduling algorithms with the reliability goal are designed. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to generate mutant mice containing the Acvrl1 gene flanked with LoxP sequences to allow conditional deletion of Acvrl1 by the LoxP/Cre system. Such mice may facilitate the development of brain arteriovenous malformation (BAVM) models. Methods The CRISPR/Cas9 technique was used to edit Acvrl1 . Two single guide RNAs (sgRNAs) with recognition sites on intron 3 and 8 and a donor vector that was homologous with the targeted gene and contained two LoxP sequences were designed and constructed. The in vitro -synthesized sgRNA, Cas9 mRNA and donor vectors were injected into mouse zygotes, which were then transferred into pseudopregnant mice. Neonatal mutant mice were identified by genotyping and sequencing. Results Two mice with a floxed Acvrl1 allele were generated at a success rate of 8.7%. The target mice, which were healthy and fertile, were obtained through interbreeding. Conclusion CRISPR/Cas9 is a reliable gene-editing tool, and is able to efficiently modify Acvrl1 and create the target mice. [ABSTRACT FROM AUTHOR]

Abstract: Fatty liver is a significant risk factor for liver transplantation, and accounts for nearly half of the livers rejected from the donor pool. We hypothesized that metabolic preconditioning via ex vivo perfusion of the liver graft can reduce fat content and increase post-transplant survival to an acceptable range. We describe a perfusate medium containing agents that promote the defatting of hepatocytes and explanted livers. Defatting agents were screened on cultured hepatocytes made fatty by pre-incubation with fatty acids. The most effective agents were then used on fatty livers. Fatty livers were isolated from obese Zucker rats and normothermically perfused with medium containing a combination of defatting agents. This combination decreased the intracellular lipid content of cultured hepatocytes by 35% over 24h, and of perfused livers by 50% over 3h. Metabolite analysis suggests that the defatting cocktail upregulated both lipid oxidation and export. Furthermore, gene expression analysis for several enzymes and transcription factors involved in fatty acid oxidation and triglyceride clearance were elevated. We conclude that a cocktail of defatting agents can be used to rapidly clear excess lipid storage in fatty livers, thus providing a new means to recondition donor livers deemed unacceptable or marginally acceptable for transplantation. [Copyright &y& Elsevier]

Liver transplantation is often the only effective treatment for end stage liver diseases resulting from cirrhosis, hepatitis, progressive jaundice, and biliary atresia. Hypothermic machine perfusion (HMP) preservation may enhance donor pool by extending preservation time and reclaiming marginal donor livers including those from non-heart beating donors (NHBD), as demonstrated in the kidney. However, current HMP protocols have not been successful in improving extended preservation of livers and the major cause of preservation injury remains unknown. An intravital microscopy study was conducted to understand the flow dynamics of sinusoidal perfusion during 24 h HMP with cold modified University of Wisconsin (UW) solution. Fluorescein isothiocynate (FITC) labeled albumin was utilized to visualize microvascular space and FITC labeled red blood cells (RBCs) were used to visualize flow dynamics during HMP. A heterogeneous flow pattern with regions of red cell stasis was observed after 24-h HMP. To examine the cause of red cell stasis, intravital and confocal microscopy studies of endothelial cells (ECs) structure labeled with DiI acetylated low-density lipoprotein (DiI acLDL) were conducted. These studies suggest that morphological changes in EC structures occurred during 24 h HMP, which may cause obstruction to the sinusoidal flow. Histological findings confirm these results. As a result, heterogeneous flow pattern, red cell stasis, and edema occur, which may lead to the failure of these tissues following extended HMP. [Copyright &y& Elsevier]

Abstract: Background: Burn injury (BI) is associated with insulin resistance (IR) and hyperglycemia which complicate clinical management. We investigated the impact of BI on glucose metabolism in a rabbit model of BI using a combination of positron emission tomography (PET) and stable isotope studies under euglycemic insulin clamp (EIC) conditions. Materials and methods: Twelve male rabbits were subjected to either full-thickness BI (B) or sham burn. An EIC condition was established by constant infusion of insulin, concomitantly with a variable rate of dextrose infusion 3 d after treatment. PET imaging of the hind limbs was conducted to determine the rates of peripheral O2 and glucose utilization. Each animal also received a primed constant infusion of [6,6-2H2] glucose to determine endogenous glucose production. Results: The fasting blood glucose in the burned rabbits was higher than that in the sham group. Under EIC conditions, the sham burn group required more exogenous dextrose than the B group to maintain blood glucose at physiological levels (22.2 ± 2.6 versus 13.3 ± 2.9 mg/min, P < 0.05), indicating a state of IR. PET imaging demonstrated that the rates of O2 consumption and 18F 2-fluoro-2-deoxy-D-glucose utilization by skeletal muscle remained at similar levels in both groups. Hepatic gluconeogenesis determined by the stable isotope tracer study was found significantly increased in the B group. Conclusions: These findings demonstrated that hyperglycemia and IR develop during the early “flow phase” after BI. Unsuppressed hepatic gluconeogenesis, but not peripheral skeletal muscular utilization of glucose, contributes to hyperglycemia at this stage. [Copyright &y& Elsevier]

Background: The shortage in donor livers has led to increased use of allografts derived from donation after cardiac death (DCD). The compromised viability in these livers leads to inferior post-transplantation allograft function and survival compared with donation after brain death (DBD) donor grafts. In this study, we reconditioned DCD livers using an optimized normothermic machine perfusion system. Methods: Livers from 12 Yorkshire pigs (20–30 kg) were subjected to either 0 min (WI-0 group, n = 6) or 60 min (WI-60 group, n = 6) of warm ischemia and 2 h of cold storage in UW solution, followed by 4 h of oxygenated sanguineous normothermic machine perfusion. Liver viability and metabolic function were analyzed hourly. Results: Warm ischemic livers showed elevated transaminase levels and reduced ATP concentration. After the start of machine perfusion, transaminase levels stabilized and there was recovery of tissue ATP, coinciding with an increase in bile production. These parameters reached comparable levels to the control group after 1 h of machine perfusion. Histology and gross morphology confirmed recovery of the ischemic allografts. Conclusion: Our data demonstrate that metabolic and functional parameters of livers with extended warm ischemic time (60 min) can be significantly improved using normothermic machine perfusion. We hereby compound the existing body of evidence that machine perfusion is a viable solution for reconditioning marginal organs. [ABSTRACT FROM AUTHOR]