HFR Code: A Flexible Replication Scheme for Cloud Storage Systems

Fractional repetition (FR) codes are a family of repair-efficient storage codes that provide exact and uncoded node repair at the minimum bandwidth regenerating point. The advantageous repair properties are achieved by a tailor-made two-layer encoding scheme which concatenates an outer maximum-distance-separable (MDS) code and an inner repetition code. In this paper, we generalize the application of FR codes and propose heterogeneous fractional repetition (HFR) code, which is adaptable to the scenario where the repetition degrees of coded packets are different. We provide explicit code constructions by utilizing group divisible designs, which allow the design of HFR codes over a large range of parameters. The constructed codes achieve the system storage capacity under random access repair and have multiple repair alternatives for node failures. Further, we take advantage of the systematic feature of MDS codes and present a novel design framework of HFR codes, in which storage nodes can be wisely partitioned into clusters such that data reconstruction time can be reduced when contacting nodes in the same cluster.Comment: Accepted for publication in IET Communications, Jul. 201

Development of novel orthogonal genetic circuits, based on extracytoplasmic function (ECF) σ factors

The synthetic biology field aims to apply the engineering 'design-build-test-learn' cycle for the implementation of synthetic genetic circuits modifying the behavior of biological systems. In order to reach this goal, synthetic biology projects use a set of fully characterized biological parts that subsequently are assembled into complex synthetic circuits following a rational, model-driven design. However, even though the bottom-up design approach represents an optimal starting point to assay the behavior of the synthetic circuits under defined conditions, the rational design of such circuits is often restricted by the limited number of available DNA building blocks. These usually consist only of a handful of transcriptional regulators that additionally are often borrowed from natural biological systems. This, in turn, can lead to cross-reactions between the synthetic circuit and the host cell and eventually to loss of the original circuit function. Thus, one of the challenges in synthetic biology is to design synthetic circuits that perform the designated functions with minor cross-reactions (orthogonality). To overcome the restrictions of the widely used transcriptional regulators, this project aims to apply extracytoplasmic function (ECF) σ factors in the design novel orthogonal synthetic circuits. ECFs are the smallest and simplest alternative σ factors that recognize highly specific promoters. ECFs represent one of the most important mechanisms of signal transduction in bacteria, indeed, their activity is often controlled by anti-σ factors. Even though it was shown that the overexpression of heterologous anti-σ factors can generate an adverse effect on cell growth, they represent an attractive solution to control ECF activity. Finally, to date, we know thousands of ECF σ factors, widespread among different bacterial phyla, that are identifiable together with the cognate promoters and anti-σ factors, using bioinformatic approaches. All the above-mentioned features make ECF σ factors optimal candidates as core orthogonal regulators for the design of novel synthetic circuits. In this project, in order to establish ECF σ factors as standard building blocks in the synthetic biology field, we first established a high throughput experimental setup. This relies on microplate reader experiments performed using a highly sensitive luminescent reporter system. Luminescent reporters have a superior signal-to-noise ratio when compared to fluorescent reporters since they do not suffer from the high auto-fluorescence background of the bacterial cell. However, they also have a drawback represented by the constant light emission that can generate undesired cross-talk between neighboring wells on a microplate. To overcome this limitation, we developed a computational algorithm that corrects for luminescence bleed-through and estimates the “true” luminescence activity for each well of a microplate. We show that the correcting algorithm preserves low-level signals close to the background and that it is universally applicable to different experimental conditions. In order to simplify the assembly of large ECF-based synthetic circuits, we designed an ECF toolbox in E. coli. The toolbox allows for the combinatorial assembly of circuits into expression vectors, using a library of reusable genetic parts. Moreover, it also offers the possibility of integrating the newly generated synthetic circuits into four different phage attachment (att) sites present in the genome of E. coli. This allows for a flawless transition between plasmid-encoded and chromosomally integrated genetic circuits, expanding the possible genetic configurations of a given synthetic construct. Moreover, our results demonstrate that the four att sites are orthogonal in terms of the gene expression levels of the synthetic circuits. With the purpose of rationally design ECF-based synthetic circuits and taking advantage of the ECF toolbox, we characterized the dynamic behavior of a set of 15 ECF σ factors, their cognate promoters, and relative anti-σs. Overall, we found that ECFs are non-toxic and functional and that they display different binding affinities for the cognate target promoters. Moreover, our results show that it is possible to optimize the output dynamic range of the ECF-based switches by changing the copy number of the ECFs and target promoters, thus, tuning the input/output signal ratio. Next, by combining up to three ECF-switches, we generated a set of “genetic-timer circuits”, the first synthetic circuits harboring more than one ECF. ECF-based timer circuits sequentially activate a series of target genes with increasing time delays, moreover, the behavior of the circuits can be predicted by a set of mathematical models. In order to improve the dynamic response of the ECF-based constructs, we introduced anti-σ factors in our synthetic circuits. By doing so we first confirmed that anti-σ factors can exert an adverse effect on the growth of E. coli, thus we explored possible solutions. Our results demonstrate that anti-σ factors toxicity can be partially alleviated by generating truncated, soluble variants of the anti-σ factors and, eventually, completely abolished via chromosomal integration of the anti-σ factor-based circuits. Finally, after demonstrating that anti-σ factors can be used to generate a tunable time delay among ECF expression and target promoter activation, we designed ECF/AS-suicide circuits. Such circuits allow for the time-delayed cell-death of E. coli and will serve as a prototype for the further development of ECF/AS-based lysis circuits

Engineering failure analysis and design optimisation with HiP-HOPS

The scale and complexity of computer-based safety critical systems, like those used in the transport and manufacturing industries, pose significant challenges for failure analysis. Over the last decade, research has focused on automating this task. In one approach, predictive models of system failure are constructed from the topology of the system and local component failure models using a process of composition. An alternative approach employs model-checking of state automata to study the effects of failure and verify system safety properties. In this paper, we discuss these two approaches to failure analysis. We then focus on Hierarchically Performed Hazard Origin & Propagation Studies (HiP-HOPS) - one of the more advanced compositional approaches - and discuss its capabilities for automatic synthesis of fault trees, combinatorial Failure Modes and Effects Analyses, and reliability versus cost optimisation of systems via application of automatic model transformations. We summarise these contributions and demonstrate the application of HiP-HOPS on a simplified fuel oil system for a ship engine. In light of this example, we discuss strengths and limitations of the method in relation to other state-of-the-art techniques. In particular, because HiP-HOPS is deductive in nature, relating system failures back to their causes, it is less prone to combinatorial explosion and can more readily be iterated. For this reason, it enables exhaustive assessment of combinations of failures and design optimisation using computationally expensive meta-heuristics. (C) 2010 Elsevier Ltd. All rights reserved

Resistant And Susceptible BIB Designs

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