Backup Circuits Research Articles

Embedded SRAM and Cortex-M0 Core with Backup Circuits using a 60-nm Crystalline Oxide Semiconductor for Power Gating

Using data retention circuits that include crystalline oxide semiconductor transistors as backup circuits for power gating, a processor system can reduce standby leakage current significantly. This is effective in the Internet of Things (IoT) applications that require standby power reduction. The crystalline oxide semiconductor transistor can constitute a nonvolatile data retention circuit easily because it exhibits significantly lower off-state current than a silicon transistor and is highly compatible with a CMOS logic circuit. The backup circuit can achieve 2-clock-cycle data backup and 4-clock-cycle data restore; thus, the processor system can efficiently perform temporally fine-grained power gating and can achieve longer standby times. Furthermore, area overheads due to the backup circuits are kept very small because the crystalline oxide semiconductor transistors are stacked on silicon transistors.

Embedded SRAM and Cortex-M0 Core Using a 60-nm Crystalline Oxide Semiconductor

Using data retention circuits that include crystalline oxide semiconductor transistors as backup circuits for power gating, a processor system can reduce standby leakage current significantly. This is effective in the Internet of Things (IoT) applications that require standby power reduction. The crystalline oxide semiconductor transistor can constitute a nonvolatile data retention circuit easily because it exhibits significantly lower off-state current than a silicon transistor and is highly compatible with a CMOS logic circuit. The backup circuit can achieve 2-clock-cycle data backup and 4-clock-cycle data restore; thus, the processor system can efficiently perform temporally fine-grained power gating and can achieve longer standby times. Furthermore, area overheads due to the backup circuits are kept very small because the crystalline oxide semiconductor transistors are stacked on silicon transistors.

Abstract 23: Identification of a Novel Intracellular Cholesteryl Ester Hydrolase (CES3) in Human Macrophages: Compensatory Increase Following CES1 Silencing

Removal of free cholesterol (FC) from lesion-associated macrophage foam cells represents the major mechanism for reducing the lipid burden of atherosclerotic plaques and intracellular cholesteryl ester (CE) hydrolysis is recognized as the rate-limiting step in this process. We have earlier reported cloning of human macrophage CE hydrolase (gene symbol CES1) that associated with cytoplasmic lipid droplets and enhanced cellular CE mobilization. Macrophage-specific transgenic expression of CES1 attenuated diet-induced atherosclerosis and lesion necrosis in ldlr -/- mice. Several enzymes have since been identified as intracellular CE hydrolases in human macrophages and the objective of the present study was to determine the relative contribution of CES1 to the total CE hydrolytic activity in human macrophages. Immune-precipitation by CES1-specific antibody resulted in 70-80% decrease in enzyme activity indicating that CES1 is responsible for >70% of the total CE hydrolytic activity (Panel A). To examine the effects of CES1 depletion/knockdown on FC efflux, human monocyte/macrophages (THP1) were stably transfected with 4 different CES1-specific shRNA vectors (p81-p84) to generate THP1-shRNA cells; cells transfected with pRSL vector were used as controls. Despite significant reduction in CES1 expression both at mRNA and protein levels, CES1 knockdown neither decreased intracellular CE hydrolysis nor decreased FC efflux. Examination of the underlying mechanisms for the observed lack of effects of CES1 knockdown revealed a compensatory increase in the expression of a novel carboxylesterase, CES3 (Panel B). Human macrophage CES3 was identical to the reported CES3 except it lacked exon 8 and, in wild type THP1 cells it was only expressed at 29.2±6.1 percent of CES1. Transient over-expression of this novel variant of CES3 led to an increase in CE hydrolytic activity (>4 fold), mobilization of intracellular lipid droplets and reduction in cellular CE content (108.1±7.65 vs 160.9±7.00, P=0.0005), establishing CES3 as a bona fide CE hydrolase. Reciprocal backup circuits, where deficiency of a gene leads to an increase in another gene with similar function, have been described and this study provides first evidence of functional compensation in intracellular CE hydrolysis whereby increased expression of CES3 restores intracellular CE hydrolytic activity and FC efflux in CES1-deficient cells. To gain insight into the mechanisms underlying the observed increase in CES3 following CES1 deficiency in silico analyses of CES3 promoter was performed and several NF-kB binding sites were identified. Based on our earlier demonstration of a decrease in NF-kB activation by CES1 over-expression, it is speculated that conversely, deficiency of CES1 increases NF-kB activation leading to compensatory increase in CES3 expression.

Integrated Design for Backup Capacity Sharing Between IP and Wavelength Services in IP-Over-WDM Networks

Two-layered IP-over-wavelength-division-multi plexing networks supporting IP and wavelength services are becoming increasingly popular. IP services are traditional data services such as virtual private networks, web browsing, etc., whereas wavelength services are new bandwidth-intensive services with strict quality-of-service (QoS) requirements, such as telemedicine, remote visualization, etc. A generic wavelength service (circuit) may require protection from a dedicated backup circuit to meet strict QoS requirements. With the upcoming huge transmission speeds of 100 Gbps and beyond, these dedicated backup circuits will induce significant underutilization of network capacity and high operational expenditure, which can be minimized by supporting IP traffic over idle backup circuits. However, during failure of backup circuits, the IP topology must always remain connected, and this problem has been preliminarily addressed by means of a suboptimal two-step approach [Opt. Switching Networking, vol. 7, p. 196, 2010]. In this paper, we discuss the opportunities and the challenges of a one-step integrated design, and we propose new methodologies for the integrated design of wavelength and IP services, with backup capacity sharing and ensuring survivability of both the services. We consider two levels of survivability for IP services, i.e., ensuring (a) connectivity of the IP topology and (b) fully reroutable capacity for the IP topology under all single physical link failures. For both the scenarios we propose an integer linear program solution and a computationally efficient heuristic. We observe that integrated provisioning with backup capacity sharing enables much higher resource utilization allowing up to a 60% decrease in wavelength channel usage in supporting IP traffic and up to 35% in the total number of wavelength channels needed to support both IP and wavelength services compared with no backup capacity sharing in our experiments.

Survivable IP topology design with re-use of backup wavelength capacity in optical backbone networks

In IP-over-WDM networks, wavelength circuits are often protected by dedicated backup circuits. Especially with future deployment of 100 G transmission systems, this will induce huge under-utilization of backup resources. Network utilization can be boosted by loaning the idle backup circuits to preemptible IP/packet services. Unfortunately, if the idle backup circuits are loaned to support IP requests then, in case of failure of the backup circuit, IP demands over the backup circuit get preempted. So, the choice of the backup circuits that can be loaned to IP/packet services must be carefully preplanned, since, in order to fully reroute the preempted IP traffic, the IP topology must remain connected. Note that a single failure in the WDM layer may affect both the links that are directly interrupted by the failure and also those links which get preempted due to the failure. Thus, only those backup circuits can be loaned which do not disconnect the IP topology in case of a failure. In this paper, we propose a mathematical formulation for the design of survivable IP topology with re-use of backup wavelength capacity. We observe that borrowing idle backup capacity to preemptible IP traffic enables much higher resource utilization, allowing for relevant decrease of network cost, and that we can still ensure combined survivability of both IP and wavelength services. A fast and computationally efficient heuristic approach is also presented.

Regulatory back-up circuit of medaka Wt1 co-orthologs ensures PGC maintenance

In mammals, the Wilms' tumor suppressor gene, Wt1, encodes a transcription factor critical for development of the urogenital system. In teleost fish, however, two wt1 genes have been identified. In medaka wt1a is expressed in the lateral plate mesoderm during early embryogenesis. Later in development, wt1a is additionally expressed in the somatic cells of the gonadal primordium. We show here for the first time that in teleosts wt1 gene expression is observed during gonad development. Wt1b is expressed later during embryogenesis and is not expressed in the gonadal primordium. Analysis of morpholino knockdown experiments revealed functions of wt1 genes in pronephros development. Unexpectedly, by down-regulating Wt1a protein we observed wt1b expression during embryogenesis in the wildtype wt1a expression domains including somatic cells of the gonadal primordium. Interestingly, neither wt1a nor wt1b morphants showed effects on the gonad development, whereas the double knockdown of wt1a and wt1b displayed strong influences on the number of primordial germ cell (PGC) during gonad development. Our results indicate that medaka wt1 co-orthologs show genetic redundancy in PGC maintenance or survival through responsive backup circuits. This provides first evidence for a conditional co-regulation of these genes within a transcriptional network.

Contextual Specificity in Peptide-Mediated Protein Interactions

Most biological processes are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. Although sufficient to ensure binding, these linear motifs alone are usually too short to achieve the high specificity observed, and additional contacts are often encoded in the residues surrounding the motif (i.e. the context). Here, we systematically identified all instances of peptide-mediated protein interactions of known three-dimensional structure and used them to investigate the individual contribution of motif and context to the global binding energy. We found that, on average, the context is responsible for roughly 20% of the binding and plays a crucial role in determining interaction specificity, by either improving the affinity with the native partner or impeding non-native interactions. We also studied and quantified the topological and energetic variability of interaction interfaces, finding a much higher heterogeneity in the context residues than in the consensus binding motifs. Our analysis partially reveals the molecular mechanisms responsible for the dynamic nature of peptide-mediated interactions, and suggests a global evolutionary mechanism to maximise the binding specificity. Finally, we investigated the viability of non-native interactions and highlight cases of potential cross-reaction that might compensate for individual protein failure and establish backup circuits to increase the robustness of cell networks.

The regulatory utilization of genetic redundancy through responsive backup circuits.

Functional redundancies, generated by gene duplications, are highly widespread throughout all known genomes. One consequence of these redundancies is a tremendous increase to the robustness of organisms to mutations and other stresses. Yet, this very robustness also renders redundancy evolutionarily unstable, and it is, thus, predicted to have only a transient lifetime. In contrast, numerous reports describe instances of functional overlaps that have been conserved throughout extended evolutionary periods. More interestingly, many such backed-up genes were shown to be transcriptionally responsive to the intactness of their redundant partner and are up-regulated if the latter is mutationally inactivated. By manual inspection of the literature, we have compiled a list of such "responsive backup circuits" in a diverse list of species. Reviewing these responsive backup circuits, we extract recurring principles characterizing their regulation. We then apply modeling approaches to explore further their dynamic properties. Our results demonstrate that responsive backup circuits may function as ideal devices for filtering nongenetic noise from transcriptional pathways and obtaining regulatory precision. We thus challenge the view that such redundancies are simply leftovers of ancient duplications and suggest they are an additional component to the sophisticated machinery of cellular regulation. In this respect, we suggest that compensation for gene loss is merely a side effect of sophisticated design principles using functional redundancy.

Up to Speed

Mice are already jittery, so giving them amphetamines might seem superfluous. But a new study suggests that Ecstasy--one type of amphetamine--can restore movement in mice suffering symptoms similar to those of Parkinson's disease. The work hints that the brain carries back-up circuits for controlling movement and might help scientists develop new drugs to combat the incurable disease.

Transcription control reprogramming in genetic backup circuits

A key question in molecular genetics is why severe mutations often do not result in a detectably abnormal phenotype. This robustness was partially ascribed to redundant paralogs that may provide backup for one another in case of mutation. Mining mutant viability and mRNA expression data in Saccharomyces cerevisiae, we found that backup was provided predominantly by paralogs that are expressed dissimilarly in most growth conditions. We considered that this apparent inconsistency might be resolved by a transcriptional reprogramming mechanism that allows the intact paralog to rescue the organism upon mutation of its counterpart. We found that in wild-type cells, partial coregulation across growth conditions predicted the ability of paralogs to alter their transcription patterns and to provide backup for one another. Notably, the sets of regulatory motifs that controlled the paralogs with the most efficient backup activity deliberately overlapped only partially; paralogs with highly similar or dissimilar sets of motifs had suboptimal backup activity. Such an arrangement of partially shared regulatory motifs reconciles the differential expression of paralogs with their ability to back each other up.

Urban Distribution Network Investment Criteria for Reliability Adequacy

Distribution planning is a complex decision-making process usually formulated as a multiobjective optimization problem. The optimal solutions represent the best possible tradeoff between network investment costs, energy loss costs, and reliability costs. In the context of optimal distribution planning, we study the dependence of backup-circuit investment decisions on the cost of energy not supplied. The study results establish investment decision-making criteria for reliability adequacy. The criteria may be used to assess what is a reasonable investment on backup circuits and to evaluate the adequacy of existing backup circuit with respect to the valuation of energy not supplied.