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Regenerative medicine, as a gospel for masses of incurable diseases, holds great promise for replacing damaged tissue and/or stimulating the organisms’ own repair mechanisms to replenish the damaged ones. One of the challenges in developing regenerative medicines is the lack of reliable and cost effective in vitro and in vivo models for assessing cell self-renewal and tissue regeneration. Zebrafish, human embryonic carcinoma cells (EC cells) and human embryonic stem cells (hES cells) were developed in this project to explore the possible function and mechanism of a series of novel small molecules. Multiple techniques including in-situ hybridization, quantitative real-time PCR, fluorescence-activated cell sorting, RNAi high–throughput screening and kinase profiling, etc. were used to investigate the biological activities of these compounds in relevant cellular or animal models. Based on the data gained so far, it is believed that compound 672 is able to increase stem cell proliferation in vitro and zebrafish fin repair in vivo in ERK1-dependent manner, acting through interacting with insulin receptor substrate-1 (IRS-1). The other compound 689 was shown to accelerate the growth of stem cells and fin repair through preventing cell death by upregulating superoxide dismutase 2 (SOD2).

A novel non-linear perturbation theory based on the characteristic equations for structural dynamic systems is developed, which can provide an exact relationship between the perturbation of structural parameters and the perturbation of modal parameters. Then, depending on information about different types of the measured vibration modal data available, a system of governing equations based on the developed theory is derived, which can be utilised for general applications, such as eigendata modification, model updating, and damage identification, suitable for all types of structures, including framed structures and continua. A number of computational procedures based on the derived non-linear governing equations are presented for structural damage identification, which can be suitable for various cases of the measured vibration modal data available, such as only natural frequencies, complete mode shapes, locally complete mode shapes, and incomplete mode shapes. The effectiveness and convergence performance for the proposed approaches are demonstrated by various numerical examples, and the sensitivities of many factors to inverse predictions of structural damage are also investigated. The results for different types of structures, either framed structures or continua, indicate that the proposed approaches can be successful in not only predicting the location of damage but also in determining the extent of structural damage, while at the same time information about only a limited amount of the measured modal data is required. Furthermore, it is found that the proposed approaches are capable of providing information on the exact expanded damaged mode shapes, even if a very limited DOF's readings are available. Structural modelling problems, which have to be considered in structural analysis and damage identification, are discussed. It is shown that structural damage can be identified correctly from the proposed approaches using information about different types of the measured modal data, regardless of different structural models considered and different types of elements used. Therefore, a suitable structural model can be selected in order to properly identify structural damage depending on the available information about modal data

The failure of the buried pipeline are rare events, and when it occurs, it poses a significant threat to the environment, human lives, and nearby assets. The performance of the buried pipeline is analysed based on the pipe failure modes such as pipe ovality, buckling pressure, and total axial and circumferential stresses. Also, the input parameters for pipe and soil properties are affected by imprecision and vagueness, particularly in the process of estimating the values. In the literature, many researchers have sought for effective methods to compute the reliability of buried pipe by considering the effect of uncertain variables. However, the existing methods such as Monte Carlo simulation are limited because of their computational capability. Often, they can only account for the aleatory type of uncertainty. Furthermore, with the increasing need in the use of buried pipelines, developing a robust and effective framework becomes necessary to overcome or mitigate against the possibility of failure. In this research, the concept of Line Sampling (LS), Important Sampling (IS) and a combination of LS and IS have been adapted for time-dependent reliability analysis of buried pipe. Similarly, a fuzzy-subset simulation framework is developed for the performance analysis of buried pipe considering aleatory (random) and epistemic (fuzzy) uncertainty. The structural response of the buried pipe was assessed and quantified based on the structural failure modes. The methods open a new pathway for a structured approach with a good computational efficiency based on complete probability and non-probability description of input parameters. The performance of buried pipe is also assessed based on fuzzy robustness measure, which is a dimensionless measure used to account for the impact of the uncertain variables. The approach gains its efficiency by scrutinising the structural robustness at every membership level with respect to various degrees of uncertainty. The principle of fuzzy set and a Hybrid GA-GAM optimisation algorithm is integrated to form a framework employed to determine a robust and acceptable design for buried pipe. The purpose of the approach is to optimise the design variable while considering the adverse effect of the uncertain fuzzy variables. The outcome based on the methods mentioned above demonstrates the importance of accounting the effects of uncertain variables. The reliability method based on fuzzy approach has been extended to estimate the optimal time for the maintenance of the buried pipeline. The strategy aimed at assessing the cost-efficiency required for the determination of the optimal time for maintenance using multi-objective optimisation based on the fuzzy reliability, risk, and total maintenance cost. The framework suggested in this study underlines the significance of the analysis of buried pipe and provides valuable guidance for improving safety in the reliability-based design, which is demonstrated using a numerical example. The key outcome of this research shows a new insight into the analysis of buried pipe by considering the effect of aleatory and epistemic type of uncertainty.

The highway industry, a critical section of Nigeria surface transportation industry is in pressing need of methods that would enable the reliability and maintainability of their fielded system. The availability and safety of highway infrastructure is a primary objective of an economy in other to provide a satisfactory level of service to road users and overcome the practical challenges from dissimilar highway assets. A large proportion of highway assets in Nigeria are classified as structurally deficient and functionally obsolete due to low discernibility of their functional failures, condition assessment and maintenance programmes which are often neglected until a catastrophic failure occurs. This research attempt to reveal ways for sound decision making to address the functional failures and structural defects and deterioration associated with highway assets by utilising UK datasets. The functional failures and structural deterioration defects are amongst the leading causes of growing failure probabilities of the road systems and networks. Thus, asset maintenance intervention is an essential task for the unified management of road assets and systems. The objectives of this research are to evaluate and develop appropriate methods that could support asset management and maintenance strategies of highway infrastructure asset and systems. A qualitative approach was initiated to develop a preventive maintenance strategy using a reliability centred maintenance approach to propose a maintenance plan for the newly fielded highway system capturing key highway assets. After that quantitative techniques such as risk-based inspection, reliability growth analysis, Markov Chain deterioration modelling and treatment renewal costing were piloted using real-time UK highway maintenance data sets from Network Maintenance Management System (NMMS) and highway condition data from Surface Condition Assessment of National Network of Roads (SCANNER) Survey. Illustrations are presented to validate the proposed methods for preventing functional failure occurrences and deterioration of highway asset by prioritising maintenance based on failure severity and system reliability. The proposed risk and reliability-based maintenance approaches can be utilised when forming a preservation strategy to avoid the functional failure and decadence of fielded highway assets.

Reinforcement corrosion is one of the major causes of deterioration of reinforced concrete structures exposed to aggressive environments. Deterioration caused by reinforcement corrosion reduces the serviceability and load bearing capacity of the concrete structures to an extent of serious structural failure. Consequently, this increases the resources required for the maintenance and rehabilitation over time. Due to uncertainties associated with the performance deterioration, it is difficult to accurately assess the residual strength and remaining useful life of corrosion damaged concrete structure. Therefore, the reliability-based performance assessment techniques based on stochastic deterioration modelling has significant potential for assessing the present and future performance of these structures. This can be ultimately helpful in sustainable and cost-effective infrastructure management. This research presents new analytical methods for evaluating concrete crack evolution, estimating rebar bond strength degradation and predicting residual flexural strength of concrete structures affected by reinforcement corrosion. At first, cracking in cover concrete due to reinforcement corrosion is investigated by using rebar-concrete model and realistic concrete properties. The bond strength evolution of the corroded rebar is then evaluated at different stages of cover cracking by considering adhesion, confinement and corrosion pressure acting at the bond interface. Furthermore, the residual flexural strength of concrete beams is predicted with consideration of bond failure between the rebar and concrete. The gamma process is adopted for stochastic modelling of concrete crack growth and strength deterioration with uncertainties. Then, a time-dependent reliability analysis is undertaken to evaluate the probability of failure in serviceability and load carrying capacity of corrosion damaged concrete beams. Optimal repair planning during the service life is also determined by balancing the cost for maintenance and the risk of structural failure. Finally, the results evaluated from the proposed methods are examined by available experimental and field data and the applicability is demonstrated by numerical examples. The results obtained show that the proposed methods are capable of evaluating the performance and can also provide risk-cost balanced repair strategy during the lifetime of corrosion damaged concrete structures. The knowledge gained from this research contributes to the better understanding of the mechanics of performance deterioration associated with reinforcement corrosion. Furthermore, the methods presented in this study could be helpful in assessing the actual state of performance deterioration and making decision regarding the optimal repair.