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Enterovirus A71 (EV-A71) and many members of the Picornaviridae family are neurotropic pathogens of global concern. These viruses are primarily transmitted through the fecal-oral route, and thus suitable animal models of oral infection are needed to investigate viral pathogenesis. An animal model of oral infection was developed using transgenic mice expressing human SCARB2 (hSCARB2 Tg), murine-adapted EV-A71/MP4 virus, and EV-A71/MP4 virus with an engineered nanoluciferase gene that allows imaging of viral replication and spread in infected mice. Next-generation sequencing of EV-A71 genomes in the tissues and organs of infected mice was also performed. Oral inoculation of EV-A71/MP4 or nanoluciferase-carrying MP4 virus stably induced neurological symptoms and death in infected 21-day-old weaned mice. In vivo bioluminescence imaging of infected mice and tissue immunostaining of viral antigens indicated that orally-inoculated virus can spread to the central nervous system and other tissues. Next-generating sequencing further identified diverse mutations in viral genomes that can potentially contribute to viral pathogenesis. This study presents an EV-A71 oral infection murine model that efficiently infects weaned mice and allows tracking of viral spread, features that can facilitate research into viral pathogenesis and neuroinvasion via the natural route of infection. Importance Enterovirus A71 (EV-A71), a positive-strand RNA virus of the Picornaviridae , poses a persistent global public health problem. EV-A71 is primarily transmitted through the fecal-oral route, and thus suitable animal models of oral infection are needed to investigate viral pathogenesis. We present an animal model of EV-A71 infection that enables the natural route of oral infection in weaned and non-immunocompromised 21-day-old hSCARB2 transgenic mice. Our results demonstrate that severe disease and death could be stably induced and viral invasion of the CNS could be replicated in this model, similar to severe real-world EV-A71 infections. We also developed a nanoluciferase-containing EV-A71 virus that can be used with this animal model to track viral spread after oral infection in real-time. Such a model offers several advantages over existing animal models, and can facilitate future research into viral spread, tissue tropism, and viral pathogenesis, all pressing issues that remain unaddressed for EV-A71 infections.

In order to improve the mechanical and optical properties of foldable AMOLED display, we integrated an ultra-thin plastic window and circular polarizer on foldable touch AMOLED. A 3mm bending radius foldable on-cell touch AMOLED prototype with plastic window or circular polarizer was demonstrated.

DJ :;sc rt(l 1I UIl s uhnlltt ed In p a rt i~l fulfi lm en t o~' th e reqlllrcrnen ts fu r tht., degree ofM~s t e r ofSClence In Enginee ring AbstractBulk water supply systems are usually designed according to deterministic design guidelines. In South Africa, design guidelines specify that a bulk storage reservoir should have a storage capacity of 48 hours of annual average daily demand (AADD), and the feeder pipe a capacity of 1.5 times AADD (CSIR, 2000). Nel & Haarhoff (1996) proposed a stochastic analysis method that allowed the reliability of a reservoir to be estimated based on a Monte Carlo analysis of consumer demand, fire water demand and pipe failures. Van Zyl et al. (2008) developed this method further and proposed a design criterion of one failure in ten years under seasonal peak conditions.In this study, a method for the optimal design of bulk water supply systems is proposed with the design variables being the configuration of the feeder pipe system, the feeder pipe diameters (i.e. capacity), and the size of the bulk storage reservoir. The stochastic analysis method is applied to determine a trade-off curve between system cost and reliability, from which the designer can select a suitable solution.Optimisation of the bulk system was performed using the multi-objective genetic algorithm, NSGA-II. As Monte Carlo sampling can be computationally expensive, especially when large numbers of simulations are required in an optimisation exercise, a compression heuristic was implemented and refined to reduce the computational effort required of the stochastic simulation. Use of the compression heuristic instead of full Monte Carlo simulation in the reliability analysis achieved computational time savings of around 75% for the optimisation of a typical system.Application of the optimisation model showed that it was able to successfully produce a set of Pareto-optimal solutions ranging from low reliability, low cost solutions to high reliability, high cost solutions. The proposed method was first applied to a typical system, resulting in an optimal reservoir size of approximately 22 h AADD and feeder pipe capacity of 2 times AADD. This solution achieved 9% savings in total system cost compared to the South African design guidelines. In addition, the optimal solution proved to have better reliability that one designed according to South African guidelines.A sensitivity analysis demonstrated the effects of changing various system and stochastic parameters from typical to low and high values. The sensitivity results revealed that the length of the feeder pipe system has the greatest impact on both the cost and reliability of the bulk system. It was also found that a single feeder pipe is optimal in most cases, and that parallel feeder pipes are only optimal for short feeder pipe lengths.The optimisation model is capable of narrowing down the search region to a handful of possible design solutions, and can thus be used by the engineer as a tool to assist with the design of the final system.