ANALYSIS OF THE NETWORK DYNAMICS OF TRANSFORMING GROWTH FACTOR - ?1 BISTABLE ACTIVATION, WITH IMPLICATIONS ON BISTABILITY AND COMBINATION THERAPY

Ph.DDOCTOR OF PHILOSOPH

Hierarchical risk assessment of water supply systems

Water supply systems are usually designed, constructed, operated, and managed in an open environment, thus they are inevitably exposed to varied uncertain threats and conditions. In order to evaluate the reliability of water supply systems under threatened conditions, risk assessment has been recognised as a useful tool to identify threats, analyse vulnerabilities and risks, and select proper mitigation measures. However, due to the complexity and uncertainty of water supply systems and risks, consistent and effective assessments are hard to accomplish by using available risk techniques. With respect to this, the current study develops a new method to assess the risks in complex water supply systems by reconsidering the organisation of risk information and risk mechanism based on the concepts of object-oriented approach. Then hierarchical assessments are conducted to evaluate the risks of components and the water supply system. The current study firstly adopts object-oriented approach, a natural and straightforward mechanism of organising information of the real world systems, to represent the water supply system at both component and system levels. At the component level, components of a water supply system are viewed as different and functional objects. Associated with each object, there are states transition diagrams that explicitly describe the risk relationships between hazards/threats, possible failure states, and negative consequences. At the system level, the water supply system is viewed as a network composed of interconnected objects. Objectoriented structures of the system represent the whole/part relationships and interconnections between components. Then based on the object states transition diagrams and object-oriented structures, this study develops two types of frameworks for risk assessment, i.e., framework of aggregative risk assessment and framework of fault tree analysis. Aggregative risk assessment is to evaluate the risk levels of components, subsystems, and the overall water supply system. While fault trees are to represent the cause-effect relationships for a specific risk in the system. Assessments of these two frameworks can help decision makers to prioritise their maintenance and management strategies in water supply systems. In order to quantitatively evaluate the framework of aggregative risk, this thesis uses a fuzzy evidential reasoning method to determine the risk levels associated with components, subsystems, and the overall water supply system. Fuzzy sets theory is used to evaluate the likelihood, severity, and risk levels associated with each hazard. Dempster-Shafer theory, a typical evidential reasoning method, is adopted to aggregate the risk levels of multiple hazards along the hierarchy of aggregative risk assessment to generate risk levels of components, subsystems, and the overall water supply system. Although fuzzy sets theory and Dempster-Shafer theory have been extensively applied to various problems, their potential of conducting aggregative risk assessments is originally explored in this thesis. Finally, in order to quantitatively evaluate the cause-effect relationships in a water supply system, fuzzy fault tree analysis is adopted in this study. Results of this analysis are likelihood of the occurrence for a specific event and importance measures of the possible contributing events. These results can help risk analysts to plan their mitigation measures to effectively control risks in the water supply system.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A priori error estimates of two fully discrete coupled schemes for Biot's consolidation model

This paper concentrates on a priori error estimates of two fully discrete coupled schemes for Biot's consolidation model based on the three-field formulation introduced by Oyarzua et al. (SIAM Journal on Numerical Analysis, 2016). The spatial discretizations are based on the Taylor-Hood finite elements combined with Lagrange elements for the three primary variables. For time discretization, we consider two methods. One uses the backward Euler method, and the other applies a combination of the backward Euler and Crank-Nicolson methods. A priori error estimates show that the two schemes are unconditionally convergent with optimal error orders. Detailed numerical experiments are presented to validate the theoretical analysis

Prediction of the post-translational modifications of adipokinetic hormone receptors from solitary to eusocial bees

Adipokinetic hormone receptor (AKHR) was regarded as the crucial regulator of lipid consuming, but now has been renewed as a pluripotent neuropeptide G protein-coupled receptor. It has been identified in all sequenced bee genomes from the solitary to the eusocial. In the current study, we try to clarify the transitions of AKHR on lipid utilization and other potential functions from solitary to eusocial bees. The results showed that the AKHRs were divided into different groups based on their social complexity approximately. Nevertheless, the critical motifs and tertiary structures were highly conserved. As to the post-translational modifications, the eusocial possessed more phosphorylation residues and modification patterns, which might be due to the necessity of more diverse functions. These results suggest that AKHRs are highly conserved on both primary motifs and tertiary structures, but more flexible on posttranslational modifications so as to accommodate to more complicated eusocial life

Assessment of Potential Risks of Dietary RNAi to a Soil Micro-arthropod, \u3cem\u3eSinella curviseta\u3c/em\u3e Brook (Collembola: Entomobryidae)

RNAi-based genetically engineered (GE) crops for the management of insect pests are likely to be commercialized by the end of this decade. Without a workable framework for conducting the ecological risk assessment (ERA) and a standardized ERA protocol, however, the utility of RNAi transgenic crops in pest management remains uncertain. The overall goal of this study is to assess the risks of RNAi-based GE crops on a non-target soil micro-arthropod, Sinella curviseta, which could be exposed to plant-protected dsRNAs deposited in crop residues. Based on the preliminary research, we hypothesized that insecticidal dsRNAs targeting at the western corn rootworm, Diabrotica virgifera virgifera, a billion-dollar insect pest, has no adverse impacts on S. curviseta, a soil decomposer. Following a tiered approach, we tested this risk hypothesis using a well-designed dietary RNAi toxicity assay. To create the worst-case scenario, the full-length cDNA of v-ATPase subunit A from S. curviseta were cloned and a 400 bp fragment representing the highest sequence similarity between target pest and non-target arthropods was selected as the template to synthesize insecticidal dsRNAs. Specifically, 10-days-old S. curviseta larvae were subjected to artificial diets containing v-ATPase A dsRNAs from both D. v. virgifera (dsDVV) and S. curviseta (dsSC), respectively, a dsRNA control, β-glucuronidase, from plant (dsGUS), and a vehicle control, H2O. The endpoint measurements included gene expression profiles, survival, and life history traits, such as developmental time, fecundity, hatching rate, and body length. Although, S. curviseta larvae developed significantly faster under the treatments of dsDVV and dsSC than the vehicle control, the combined results from both temporal RNAi effect study and dietary RNAi toxicity assay support the risk hypothesis, suggesting that the impacts of ingested arthropod-active dsRNAs on this representative soil decomposer are negligible

Dynamic and Functional Characteristics of Predominant Species in Industrial Paocai as Revealed by Combined DGGE and Metagenomic Sequencing

The microbial community during the fermentation of industrial paocai, a lactic acid fermented vegetable food, was investigated via combined denaturing gradient gel electrophoresis (DGGE) and metagenomic sequencing. Firmicutes and Proteobacteria were identified as the dominant phyla during the fermentation. DGGE results of the bacterial community analysis showed that many genera were observed during the fermentation of industrial paocai, but the same predominant genus and species were observed: Lactobacillus and Lactobacillus (L.) alimentarius/L. paralimentarius. The abundance of L. alimentarius/L. paralimentarius increased fast during the initial stage of fermentation and approximately remained constant during the later stage. Metagenomic sequencing was used to finally identify the predominant species and their genetic functions. Metabolism was the primary functions of the microbial community in industrial paocai fermentation, including carbohydrate metabolism (CM), overview (OV), amino acid metabolism (AAM), nucleotide metabolism (NM), energy metabolism (EM), etc. The predominant species L. alimentarius and L. paralimentarius were involved in plenty of pathways in metabolism and played different roles in the metabolism of carbohydrate, amino acid, lipid to form flavor compounds during industrial paocai fermentation. This study provided valuable information about the predominant species in industrial paocai and its functional properties, which could enable us to advance our understanding of the fermentation mechanism during fermentation of industrial paocai. Our results will advance the understanding of the microbial roles in the industrial paocai fermentation and provide a theoretical basis for improving the quality of industrial paocai products

Stable Reference Gene Selection for RT-qPCR Analysis in Nonviruliferous and Viruliferous \u3cem\u3eFrankliniella occidentalis\u3c/em\u3e

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a reliable technique for measuring and evaluating gene expression during variable biological processes. To facilitate gene expression studies, normalization of genes of interest relative to stable reference genes is crucial. The western flower thrips Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), the main vector of tomato spotted wilt virus (TSWV), is a destructive invasive species. In this study, the expression profiles of 11 candidate reference genes from nonviruliferous and viruliferous F. occidentalis were investigated. Five distinct algorithms, geNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder, were used to determine the performance of these genes. geNorm, NormFinder, BestKeeper, and RefFinder identified heat shock protein 70 (HSP70), heat shock protein 60 (HSP60), elongation factor 1 α, and ribosomal protein l32 (RPL32) as the most stable reference genes, and the ΔCt method identified HSP60, HSP70, RPL32, and heat shock protein 90 as the most stable reference genes. Additionally, two reference genes were sufficient for reliable normalization in nonviruliferous and viruliferous F. occidentalis. This work provides a foundation for investigating the molecular mechanisms of TSWV and F. occidentalis interactions