Holistic, data-driven, service and supply chain optimisation: linked optimisation.

The intensity of competition and technological advancements in the business environment has made companies collaborate and cooperate together as a means of survival. This creates a chain of companies and business components with unified business objectives. However, managing the decision-making process (like scheduling, ordering, delivering and allocating) at the various business components and maintaining a holistic objective is a huge business challenge, as these operations are complex and dynamic. This is because the overall chain of business processes is widely distributed across all the supply chain participants; therefore, no individual collaborator has a complete overview of the processes. Increasingly, such decisions are automated and are strongly supported by optimisation algorithms - manufacturing optimisation, B2B ordering, financial trading, transportation scheduling and allocation. However, most of these algorithms do not incorporate the complexity associated with interacting decision-making systems like supply chains. It is well-known that decisions made at one point in supply chains can have significant consequences that ripple through linked production and transportation systems. Recently, global shocks to supply chains (COVID-19, climate change, blockage of the Suez Canal) have demonstrated the importance of these interdependencies, and the need to create supply chains that are more resilient and have significantly reduced impact on the environment. Such interacting decision-making systems need to be considered through an optimisation process. However, the interactions between such decision-making systems are not modelled. We therefore believe that modelling such interactions is an opportunity to provide computational extensions to current optimisation paradigms. This research study aims to develop a general framework for formulating and solving holistic, data-driven optimisation problems in service and supply chains. This research achieved this aim and contributes to scholarship by firstly considering the complexities of supply chain problems from a linked problem perspective. This leads to developing a formalism for characterising linked optimisation problems as a model for supply chains. Secondly, the research adopts a method for creating a linked optimisation problem benchmark by linking existing classical benchmark sets. This involves using a mix of classical optimisation problems, typically relating to supply chain decision problems, to describe different modes of linkages in linked optimisation problems. Thirdly, several techniques for linking supply chain fragmented data have been proposed in the literature to identify data relationships. Therefore, this thesis explores some of these techniques and combines them in specific ways to improve the data discovery process. Lastly, many state-of-the-art algorithms have been explored in the literature and these algorithms have been used to tackle problems relating to supply chain problems. This research therefore investigates the resilient state-of-the-art optimisation algorithms presented in the literature, and then designs suitable algorithmic approaches inspired by the existing algorithms and the nature of problem linkages to address different problem linkages in supply chains. Considering research findings and future perspectives, the study demonstrates the suitability of algorithms to different linked structures involving two sub-problems, which suggests further investigations on issues like the suitability of algorithms on more complex structures, benchmark methodologies, holistic goals and evaluation, processmining, game theory and dependency analysis

A Method for Specifying Complex Real-Time Systems With Application to an Experimental Variable Stability Helicopter

Engineering systems increasingly contain a significant element of embedded software. The specification of such systems causes problems because of the diversity of the sub-systems which they contain. For example, in modem aerospace systems a combination of mechanical, electrical, hydraulic and digital sub-systems need to function together in a safety-critical manner. The need is for a uniform means of specification which spans the whole diversity of sub-systems and which serves both to verify and to validate the functional aspects of the total system

The roles of Thailand Science Park in supporting the development of innovation clusters in Thailand : comparative case study - Thailand Science Park, Surrey Research Park, and Hong Kong Science and Technology Park

This thesis investigates the role of Science Parks (SPs) in supporting the development of Innovation Clusters (ICs), with a specific focus on Thailand Science Park (TSP). It adopts a comparative approach, examining the operational strategies of TSP alongside Surrey Research Park (SRP) in the UK and Hong Kong Science and Technology Park (HKSTP). The qualitative methodology is employed; questionnaires were emailed to 58 European and 13 Asian SPs, including SRP and HKSTP, to select two SPs for comparison with TSP. Subsequently, semi-structured interviews were conducted with 53 stakeholders from these three Parks. The study addresses three pivotal questions: Firstly, it explores how SPs in developing countries, like Thailand, differ in their approach to fostering long-lasting ICs compared to those in more developed economies. The research highlights unique challenges such as bureaucratic governance and cultural barriers, drawing lessons from HKSTP's flexible approach and collaborative culture. Secondly, the thesis delves into the management of R&D infrastructure, services, and networking in SPs. It reveals varied strategies across TSP, HKSTP, and SRP, underscoring the need for context-specific approaches in developing countries. Finally, the research examines the essential strategic elements for IC development in SPs, focusing on the necessity of support from policymakers and stakeholders in infrastructure, services, and financial backing. This research contributes significantly to the field by providing a comparative strategic analysis of SPs in various economic contexts, identifying strategies to address challenges, and emphasising the importance of public-private partnerships. Additionally, it offers insights into aligning performance indicators with SPs' goals, the criticality of rigorous tenant selection, and the evolving nature of infrastructure and innovation services in SPs.This thesis investigates the role of Science Parks (SPs) in supporting the development of Innovation Clusters (ICs), with a specific focus on Thailand Science Park (TSP). It adopts a comparative approach, examining the operational strategies of TSP alongside Surrey Research Park (SRP) in the UK and Hong Kong Science and Technology Park (HKSTP). The qualitative methodology is employed; questionnaires were emailed to 58 European and 13 Asian SPs, including SRP and HKSTP, to select two SPs for comparison with TSP. Subsequently, semi-structured interviews were conducted with 53 stakeholders from these three Parks. The study addresses three pivotal questions: Firstly, it explores how SPs in developing countries, like Thailand, differ in their approach to fostering long-lasting ICs compared to those in more developed economies. The research highlights unique challenges such as bureaucratic governance and cultural barriers, drawing lessons from HKSTP's flexible approach and collaborative culture. Secondly, the thesis delves into the management of R&D infrastructure, services, and networking in SPs. It reveals varied strategies across TSP, HKSTP, and SRP, underscoring the need for context-specific approaches in developing countries. Finally, the research examines the essential strategic elements for IC development in SPs, focusing on the necessity of support from policymakers and stakeholders in infrastructure, services, and financial backing. This research contributes significantly to the field by providing a comparative strategic analysis of SPs in various economic contexts, identifying strategies to address challenges, and emphasising the importance of public-private partnerships. Additionally, it offers insights into aligning performance indicators with SPs' goals, the criticality of rigorous tenant selection, and the evolving nature of infrastructure and innovation services in SPs

Computational Design and Experimental Validation of Functional Ribonucleic Acid Nanostructures

In living cells, two major classes of ribonucleic acid (RNA) molecules can be found. The first class called the messenger RNA (mRNA) contains the genetic information that allows the ribosome to read and translate it into proteins. The second class called non-coding RNA (ncRNA), do not code for proteins and are involved with key cellular processes, such as gene expression regulation, splicing, differentiation, and development. NcRNAs fold into an ensemble of thermodynamically stable secondary structures, which will eventually lead the molecule to fold into a specific 3D structure. It is widely known that ncRNAs carry their functions via their 3D structures as well as their molecular composition. The secondary structure of ncRNAs is composed of different types of structural elements (motifs) such as stacking base pairs, internal loops, hairpin loops and pseudoknots. Pseudoknots are specifically difficult to model, are abundant in nature and known to stabilize the functional form of the molecule. Due to the diverse range of functions of ncRNAs, their computational design and analysis have numerous applications in nano-technology, therapeutics, synthetic biology, and materials engineering. The RNA design problem is to find novel RNA sequences that are predicted to fold into target structure(s) while satisfying specific qualitative characteristics and constraints. RNA design can be modeled as a combinatorial optimization problem (COP) and is known to be computationally challenging or more precisely NP-hard. Numerous algorithms to solve the RNA design problem have been developed over the past two decades, however mostly ignore pseudoknots and therefore limit application to only a slice of real-world modeling and design problems. Moreover, the few existing pseudoknot designer methods which were developed only recently, do not provide any evidence about the applicability of their proposed design methodology in biological contexts. The two objectives of this thesis are set to address these two shortcomings. First, we are interested in developing an efficient computational method for the design of RNA secondary structures including pseudoknots that show significantly improved in-silico quality characteristics than the state of the art. Second, we are interested in showing the real-world worthiness of the proposed method by validating it experimentally. More precisely, our aim is to design instances of certain types of RNA enzymes (i.e. ribozymes) and demonstrate that they are functionally active. This would likely only happen if their predicted folding matched their actual folding in the in-vitro experiments. In this thesis, we present four contributions. First, we propose a novel adaptive defect weighted sampling algorithm to efficiently solve the RNA secondary structure design problem where pseudoknots are included. We compare the performance of our design algorithm with the state of the art and show that our method generates molecules that are thermodynamically more stable and less defective than those generated by state of the art methods. Moreover, we show when the effect of fitness evaluation is decoupled from the search and optimization process, our optimization method converges faster than the non-dominated sorting genetic algorithm (NSGA II) and the ant colony optimization (ACO) algorithm do. Second, we use our algorithmic development to implement an RNA design pipeline called Enzymer and make it available as an open source package useful for wet lab practitioners and RNA bioinformaticians. Enzymer uses multiple sequence alignment (MSA) data to generate initial design templates for further optimization. Our design pipeline can then be used to re-engineer naturally occurring RNA enzymes such as ribozymes and riboswitches. Our first and second contributions are published in the RNA section of the Journal of Frontiers in Genetics. Third, we use Enzymer to reengineer three different species of pseudoknotted ribozymes: a hammerhead ribozyme from the mouse gut metagenome, a hammerhead ribozyme from Yarrowia lipolytica and a glmS ribozyme from Thermoanaerobacter tengcogensis. We designed a total of 18 ribozyme sequences and showed the 16 of them were active in-vitro. Our experimental results have been submitted to the RNA journal and strongly suggest that Enzymer is a reliable tool to design pseudoknotted ncRNAs with desired secondary structure. Finally, we propose a novel architecture for a new ribozyme-based gene regulatory network where a hammerhead ribozyme modulates expression of a reporter gene when an external stimulus IPTG is present. Our in-vivo results show expected results in 7 out of 12 cases

Autonomous Flight, Fault, and Energy Management of the Flying Fish Solar-Powered Seaplane.

The Flying Fish autonomous unmanned seaplane is designed and built for persistent ocean surveillance. Solar energy harvesting and always-on autonomous control and guidance are required to achieve unattended long-term operation. This thesis describes the Flying Fish avionics and software systems that enable the system to plan, self-initiate, and autonomously execute drift-flight cycles necessary to maintain a designated watch circle subject to environmentally influenced drift. We first present the avionics and flight software architecture developed for the unique challenges of an autonomous energy-harvesting seaplane requiring the system to be: waterproof, robust over a variety of sea states, and lightweight for flight. Seaplane kinematics and dynamics are developed based on conventional aircraft and watercraft and upon empirical flight test data. These models serve as the basis for development of flight control and guidance strategies which take the form of a cyclic multi-mode guidance protocol that smoothly transitions between nested gain-scheduled proportional-derivative feedback control laws tuned for the trim conditions of each flight mode. A fault-tolerant airspeed sensing system is developed in response to elevated failure rates arising from pitot probe water ingestion in the test environment. The fault-tolerance strategy utilizes sensor characteristics and signal energy to combine redundant sensor measurements in a weighted voting strategy, handling repeated failures, sensor recovery, non-homogenous sensors, and periods of complete sensing failure. Finally, a graph-based mission planner combines models of global solar energy, local ocean-currents, and wind with flight-verified/derived aircraft models to provide an energy-aware flight planning tool. An NP-hard asymmetric multi-visit traveling salesman planning problem is posed that integrates vehicle performance and environment models using energy as the primary cost metric. A novel A* search heuristic is presented to improve search efficiency relative to uniform cost search. A series of cases studies are conducted with surface and airborne goals for various times of day and for multi-day scenarios. Energy-optimal solutions are identified except in cases where energy harvesting produces multiple comparable-cost plans via negative-cost cycles. The always-on cyclic guidance/control system, airspeed sensor fault management algorithm, and the nested-TSP heuristic for A* are all critical innovation required to solve the posed research challenges.Ph.D.Aerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91453/1/eubankrd_1.pd