Fault tolerant software technology for distributed computing system

Issued as Monthly reports [nos. 1-23], Interim technical report, Technical guide books [nos. 1-2], and Final report, Project no. G-36-64

Robust services in dynamic systems

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (p. 191-202).Our growing reliance on online services accessible on the Internet demands highly- available systems that work correctly without interruption. This thesis extends previous work on Byzantine-fault-tolerant replication to meet the new requirements of current Internet services: scalability and the ability to reconfigure the service automatically in the presence of a changing system membership. Our solution addresses two important problems that appear in dynamic replicated services: First, we present a membership service that provides servers and clients in the system with a sequence of consistent views of the system membership (i.e., the set of currently available servers). The membership service is designed to be scalable, and to handle membership changes mostly automatically. Furthermore, the membership service is itself reconfigurable, and tolerates arbitrary faults of a subset of the servers that are implementing it at any instant. The second part of our solution is a generic methodology for transforming replicated services that assume a fixed membership into services that support a dynamic system membership. The methodology uses the output from the membership service to decide when to reconfigure.(cont.) We built two example services using this methodology: a dynamic Byzantine quorum system that supports read and write operations, and a dynamic Byzantine state machine replication system that supports any deterministic service. The final contribution of this thesis is an analytic study that points out an obstacle to the deployment of replicated services based on a dynamic membership. The basic problem is that maintaining redundancy levels for the service state as servers join and leave the system is costly in terms of network bandwidth. To evaluate how dynamic the system membership can be, we developed a model for the cost of state maintenance in dynamic replicated services, and we use measured values from real-world traces to determine possible values for the parameters of the model. We conclude that certain deployments (like a volunteer-based system) are incompatible with the goals of large- scale reliable services. We implemented the membership service and the two example services. Our performance results show that the membership service is scalable, and our replicated services perform well, even during reconfigurations.by Rodrigo Seromenho Miragaia Rodrigues.Ph.D

Pseudomonas aeruginosa​ genetics and virulence in cystic fibrosis and bacteraemia

Pseudomonas aeruginosa ​is an opportunistic pathogen that can invade and colonise the lungs of people with cystic fibrosis (CF), cause septic shock through bacteraemia infections, and lead to serious infection of burn injuries. It is one of the most critical multi-drug resistant bacteria, and is associated with high morbidity and mortality. A total of 4,094 ​P. aeruginosa isolates were sampled from nine patients with CF over a six-month time period. These isolates were collected from sputum samples during stable, acute, and recovery timepoints from periods of sudden and rapid lung function decline, called acute pulmonary exacerbations (APEs). These isolates were previously analysed for the presence and absence of ten virulence-related phenotypes. The ​P. aeruginosa isolates were whole-genome sequenced to investigate the inter- and intra-patient genotypic diversity, associations with phenotypic diversity, and adaptation within the CF lung. Each of the nine patients with CF were colonised with a distinct clone of ​P. aeruginosa​. Six patients were infected with well-characterised, highly-transmissible strains of either the Liverpool Epidemic Strain (LES) or the Manchester Epidemic Strain (MES). The remaining three patients were infected with novel sequence types (STs); ST3307 or ST3308. Putative transmission was identified between the two patients infected with ST3307. Two large deletions in genetic regions commonly associated with progression from acute to chronic infection were identified in ST3307. The acquisition of the LES by one of the patients was very recent, estimated to have occurred within the two years prior to the study. This recent acquisition provides an insight into the immediate adaptation of P. aeruginosa to the CF lung, with adaptation observed in genetic regions associated with progression from acute to chronic ​P. aeruginosa​ infection. The timepoints for each APE within the individual patients were not associated with variation in the diversity of the populations of isolates. This was confirmed by random distribution of phylogenetic clusters with respect to each APE timepoint for most patients, suggesting that APEs, and the treatment of APEs, do not substantially affect the diversity of the ​P. aeruginosa​ population within the patient lung. Genome-wide association studies (GWAS) were carried out on the CF isolates, to investigate any associations with the ten previously-tested virulence-related phenotypes. Population structure could be effectively controlled for in this highly structured dataset, using linear mixed models. Multiple GWAS approaches were required to capture the different classes of genetic variation, resulting in the identification of biologically relevant associations for complex phenotypes, most notably a premature stop-codon in the global transcriptional regulator r​hlR,​ as well as several novel, potentially significant associations. An additional 352 ​P. aeruginosa ​isolates from patients with bacteraemia were also whole-genome sequenced. These isolates were sourced from both a local collection and from a UK-wide surveillance collection, and broadly match the defined population structure of ​P. aeruginosa.​ Three STs were overrepresented in this dataset, which are associated with virulence and multi-drug resistance; ST175, ST253 and ST395. One of these overrepresented STs, ST175, was distributed across the UK, shows significant geographical clustering and temporal signal, and is predicted to have been introduced into the UK between the late 1980s and the early 1990s. Antimicrobial resistance profiles showed that current therapeutic options are still viable for most ​P. aeruginosa bacteraemia infections, and that colistin is still effective against the most multi-drug resistant isolates

A Self-Organising Distributed Location Server for Ad Hoc Networks

Wireless networks allow communication between multiple devices (nodes) without the use of wires. Range in such networks is often limited restricting the use of networks to small offices and homes; however, it is possible to use nodes to forward packets for others thereby extending the communication range of individual nodes. Networks employing such forwarding are called Multi-Hop Ad Hoc Networks (MANETS) Discovering routes in MANETS is a challenging task given that the topology is flat and node addresses reveal nothing about their place in the network. In addition, nodes may move or leave changing the network topology quickly. Existing approaches to discovering locations involve either broadcast dissemination or broadcast route discovery throughout the entire network. The reliance on the use of techniques that use broadcast schemes restricts the size of network that the techniques are applicable to. Routing in large scale ad hoc networks is therefore achieved by the use of geographical forwarding. Each node is required to know its location and that of its neighbours so that it may use this information for forward packets. The next hop chosen is the neighbour that is closest to the destination and a number of techniques are used to handle scenarios here the network has areas void of nodes. Use of such geographical routing techniques requires knowledge of the destination's location. This is provided by location servers and the literature proposes a number of methods of providing them. Unfortunately many of the schemes are limited by using a proportion of the network that increases with size, thereby immediately limiting the scalability. Only one technique is surveyed that provides high scalability but it has a number of limitations in terms of handling node mobility and failure. Ad hoc networks have limited capacity and so the inspiration for a technique to address these shortcomings comes from observations of nature. Birds and ants are able to organise themselves without direct communication through the observation of their environment and their peers. They provide an emergent intelligence based on individual actions rather than group collaboration. This thesis attempts to discover whether software agents can mimic this by creating a group of agents to store location information in a specific location. Instead of requiring central co-ordination, the agents observe one another and make individual decisions to create an emergent intelligence that causes them to resist mobility and node failures. The new technique is called a Self Organising Location Server (SOLS) and is compared against existing approaches to location servers. Most existing techniques do not scale well whereas SOLS uses a new idea of a home location. The use of this idea and the self organising behaviour of the agents that store the information results in significant benefits in performance. SOLS significantly out performs Terminode home region, the only other scalable approach surveyed. SOLS is able to tolerate much higher node failure rates than expected in likely implementations of large scale ad hoc networks. In addition, SOLS successfully mitigates node mobility which is likely to be encountered in an ad hoc network

Microbial Metabolomics

Microbial metabolomics constitutes an integrated component of systems biology. By studying the complete set of metabolites within a microorganism and monitoring the global outcome of interactions between its development processes and the environment, metabolomics can potentially provide a more accurate snap shot of the actual physiological state of the cell. Recent advancement of technologies and post-genomic developments enable the study and analysis of metabolome. This unique contribution resulted in many scientific disciplines incorporating metabolomics as one of their “omics” platforms. This review focuses on metabolomics in microorganisms and utilizes selected topics to illustrate its impact on the understanding of systems microbiology

Responsive Polymers as Cell Surface Modifiers and 3D Healable Microenvironments

The interplay between cells and biomaterials constitutes a fertile ground to probe specific cellular functions and cues for therapeutic and research purposes. “Smart” materials encompass an extensive library that can lead to the design of dynamic multi-responsive constructs with great importance in the biomedical field. This work aims to describe diverse strategies on the modification of biological interfaces with synthetic polymers to promote the assembly of living cells and the design of multi-responsive healable cell-encapsulating constructs with interest in 3D in vitro modelling, drug delivery, cell-based therapies and tissue engineering. In the first part, cell membrane engineering approaches are introduced to create a responsive platform for the accelerated and simple formation of cellular aggregates/spheroids, and to study polymer-cell interactions by exploring biorthogonal ligand-receptor multivalent interactions under different conditions. Specifically, boronic acid- and succinimide-based copolymers were first synthesised and fully characterised by physicochemical methods, and found to bind covalently to natural moieties present on the membrane of several cell lines, which can regulate the development of cell spheroids and act as self-supporting “cellular glues”. The second part of the project is dedicated to the development of multi-responsive self-healing hydrogel nanocomposites for biomedical applications, where we further expanded the dynamic crosslinking nature of boronate ester bonds. The proposed gels could be prepared almost instantly, exhibited photo- and thermoreversible transient sol-gel type of transition with excellent healing properties, and no toxicity, which allows the system to be used as a versatile biologic delivery matrix. In summary, the results highlight novel and straightforward approaches that may pave the way to implement a biomaterial-cell platform with broad biotechnological applications

METHANOGEN METABOLIC FLEXIBILITY

Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are terpene compounds, as methanogen membranes are composed of isoprenoid lipids resulting in a higher flux through isoprenoid biosynthetic pathways compared to Eukarya and Bacteria. To assess the metabolic plasticity of methanogens, our laboratory has engineered the methanogen Methanosarcina acetivorans to produce the hemiterpene isoprene. We hypothesized that isoprene producing strains would result in a decreased growth phenotype corresponding to a depletion of metabolic precursors needed for isoprenoid membrane production. We found that the engineered methanogens responded well to the modification, directing up to 4% of total towards isoprene production and increasing overall biomass despite the additional metabolic burden. Using flux balance analysis and RNA sequencing we investigated how the engineered strains respond to isoprene production and how production can be enhanced. Advisor: Nicole R. Bua

Data trust framework using blockchain and smart contracts

Lack of trust is the main barrier preventing more widespread data sharing. The lack of transparent and reliable infrastructure for data sharing prevents many data owners from sharing their data. Data trust is a paradigm that facilitates data sharing by forcing data controllers to be transparent about the process of sharing and reusing data. Blockchain technology has the potential to present the essential properties for creating a practical and secure data trust framework by transforming current auditing practices and automatic enforcement of smart contracts logic without relying on intermediaries to establish trust. Blockchain holds an enormous potential to remove the barriers of traditional centralized applications and propose a distributed and transparent administration by employing the involved parties to maintain consensus on the ledger. Furthermore, smart contracts are a programmable component that provides blockchain with more flexible and powerful capabilities. Recent advances in blockchain platforms toward smart contracts' development have revealed the possibility of implementing blockchain-based applications in various domains, such as health care, supply chain and digital identity. This dissertation investigates the blockchain's potential to present a framework for data trust. It starts with a comprehensive study of smart contracts as the main component of blockchain for developing decentralized data trust. Interrelated, three decentralized applications that address data sharing and access control problems in various fields, including healthcare data sharing, business process, and physical access control system, have been developed and examined. In addition, a general-purpose application based on an attribute-based access control model is proposed that can provide trusted auditability required for data sharing and access control systems and, ultimately, a data trust framework. Besides auditing, the system presents a transparency level that both access requesters (data users) and resource owners (data controllers) can benefit from. The proposed solutions have been validated through a use case of independent digital libraries. It also provides a detailed performance analysis of the system implementation. The performance results have been compared based on different consensus mechanisms and databases, indicating the system's high throughput and low latency. Finally, this dissertation presents an end-to-end data trust framework based on blockchain technology. The proposed framework promotes data trustworthiness by assessing input datasets, effectively managing access control, and presenting data provenance and activity monitoring. A trust assessment model that examines the trustworthiness of input data sets and calculates the trust value is presented. The number of transaction validators is defined adaptively with the trust value. This research provides solutions for both data owners and data users’ by ensuring the trustworthiness and quality of the data at origin and transparent and secure usage of the data at the end. A comprehensive experimental study indicates the presented system effectively handles a large number of transactions with low latency

Cost- and workload-driven data management in the cloud

This thesis deals with the challenge of finding the right balance between consistency, availability, latency and costs, captured by the CAP/PACELC trade-offs, in the context of distributed data management in the Cloud. At the core of this work, cost and workload-driven data management protocols, called CCQ protocols, are developed. First, this includes the development of C3, which is an adaptive consistency protocol that is able to adjust consistency at runtime by considering consistency and inconsistency costs. Second, the development of Cumulus, an adaptive data partitioning protocol, that can adapt partitions by considering the application workload so that expensive distributed transactions are minimized or avoided. And third, the development of QuAD, a quorum-based replication protocol, that constructs the quorums in such a way so that, given a set of constraints, the best possible performance is achieved. The behavior of each CCQ protocol is steered by a cost model, which aims at reducing the costs and overhead for providing the desired data management guarantees. The CCQ protocols are able to continuously assess their behavior, and if necessary to adapt the behavior at runtime based on application workload and the cost model. This property is crucial for applications deployed in the Cloud, as they are characterized by a highly dynamic workload, and high scalability and availability demands. The dynamic adaptation of the behavior at runtime does not come for free, and may generate considerable overhead that might outweigh the gain of adaptation. The CCQ cost models incorporate a control mechanism, which aims at avoiding expensive and unnecessary adaptations, which do not provide any benefits to applications. The adaptation is a distributed activity that requires coordination between the sites in a distributed database system. The CCQ protocols implement safe online adaptation approaches, which exploit the properties of 2PC and 2PL to ensure that all sites behave in accordance with the cost model, even in the presence of arbitrary failures. It is crucial to guarantee a globally consistent view of the behavior, as in contrary the effects of the cost models are nullified. The presented protocols are implemented as part of a prototypical database system. Their modular architecture allows for a seamless extension of the optimization capabilities at any level of their implementation. Finally, the protocols are quantitatively evaluated in a series of experiments executed in a real Cloud environment. The results show their feasibility and ability to reduce application costs, and to dynamically adjust the behavior at runtime without violating their correctness

A conceptual system design and managerial complexity competency model

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Complex adaptive systems are usually difficult to design and control. There are several particular methods for coping with complexity, but there is no general approach to build complex adaptive systems. The challenges of designing complex adaptive systems in a highly dynamic world drive the need for anticipatory capacity within engineering organizations, with a goal of enabling the design of systems that can cope with an unpredictable environment. This thesis explores this question of enhancing anticipatory capacity through the study of a complex adaptive system design methodology and complexity management competencies. A general introduction to challenges and issues in complex adaptive systems design is given, since a good understanding of the industrial context is considered necessary in order to avoid oversimplification of the problem, neglecting certain important factors and being unaware of important influences and relationships. In addition, a general introduction to complex thinking is given, since designing complex adaptive systems requires a non-classical thought, while practical notions of complexity theory and design are put forward. Building on these, the research proposes a Complex Systems Life-Cycle Understanding and Design (CXLUD) methodology to aid system architects and engineers in the design and control of complex adaptive systems. Starting from a creative anticipation construct - a loosening mechanism to allow for more options to be considered, the methodology proposes a conceptual framework and a series of stages to follow to find proper mechanisms that will promote elements to desired solutions by actively interacting among themselves. To illustrate the methodology, a financial systemic risks infrastructure systems architecture development case study is presented. The final part of this thesis develops a conceptual model to analyse managerial complexity competency model from a qualitative phenomenological study perspective. The model developed in this research is called Understanding-Perception-Action (UPA) managerial complexity competency model. The results of this competency model can be used to help ease project manager’s transition into complex adaptive projects, as well as serve as a foundation to launch qualitative and quantitative research into this area of project complexity management