Bifocal lens control of myopia progression in children

This research investigated underlying issues that were critical to the success of the bifocal trial and comprised of three studies. The first study evaluated if Chinese-Canadian children were suitable subjects for the bifocal trial. The high prevalence of myopia in Chinese children suggests that genetic input plays a role in myopia development, but the rapid increase in prevalence over the last few decades indicates environmental factors are also important. Since this bifocal trial was conducted in Canada, this work aimed to determine whether Chinese children who had migrated to Canada would still have high myopia prevalence and a high rate of myopia progression. The second study determined the optimal bifocal lens power for myopia treatment and the effect of incorporating base-in prism into the bifocal. In the majority of published myopia control studies, the power of the prescribed near addition was usually predetermined in the belief that the near addition would always help to improve the near focus. In fact, the effect of near addition on the accommodative error might be quite different even for individuals in which the same magnitude of accommodation lag had been measured. Therefore, this work was necessary to guide the selection of bifocal and prism powers most suitable for the subsequent bifocal trial. The third study, the ultimate goal of this research, was to conduct a longitudinal clinical trial to determine if bifocals and prismatic bifocals could control myopia progression in children.

Geological control of physiography in Southeast Queensland: A multi-scale analysis using GIS

The study reported here, constitutes a full review of the major geological events that have influenced the morphological development of the southeast Queensland region. Most importantly, it provides evidence that the region’s physiography continues to be geologically ‘active’ and although earthquakes are presently few and of low magnitude, many past events and tectonic regimes continue to be strongly influential over drainage, morphology and topography. Southeast Queensland is typified by highland terrain of metasedimentary and igneous rocks that are parallel and close to younger, lowland coastal terrain. The region is currently situated in a passive margin tectonic setting that is now under compressive stress, although in the past, the region was subject to alternating extensional and compressive regimes. As part of the investigation, the effects of many past geological events upon landscape morphology have been assessed at multiple scales using features such as the location and orientation of drainage channels, topography, faults, fractures, scarps, cleavage, volcanic centres and deposits, and recent earthquake activity. A number of hypotheses for local geological evolution are proposed and discussed. This study has also utilised a geographic information system (GIS) approach that successfully amalgamates the various types and scales of datasets used. A new method of stream ordination has been developed and is used to compare the orientation of channels of similar orders with rock fabric, in a topologically controlled approach that other ordering systems are unable to achieve. Stream pattern analysis has been performed and the results provide evidence that many drainage systems in southeast Queensland are controlled by known geological structures and by past geological events. The results conclude that drainage at a fine scale is controlled by cleavage, joints and faults, and at a broader scale, large river valleys, such as those of the Brisbane River and North Pine River, closely follow the location of faults. These rivers appear to have become entrenched by differential weathering along these planes of weakness. Significantly, stream pattern analysis has also identified some ‘anomalous’ drainage that suggests the orientations of these watercourses are geologically controlled, but by unknown causes. To the north of Brisbane, a ‘coastal drainage divide’ has been recognized and is described here. The divide crosses several lithological units of different age, continues parallel to the coast and prevents drainage from the highlands flowing directly to the coast for its entire length. Diversion of low order streams away from the divide may be evidence that a more recent process may be the driving force. Although there is no conclusive evidence for this at present, it is postulated that the divide may have been generated by uplift or doming associated with mid-Cenozoic volcanism or a blind thrust at depth. Also north of Brisbane, on the D’Aguilar Range, an elevated valley (the ‘Kilcoy Gap’) has been identified that may have once drained towards the coast and now displays reversed drainage that may have resulted from uplift along the coastal drainage divide and of the D’Aguilar blocks. An assessment of the distribution and intensity of recent earthquakes in the region indicates that activity may be associated with ancient faults. However, recent movement on these faults during these events would have been unlikely, given that earthquakes in the region are characteristically of low magnitude. There is, however, evidence that compressive stress is building and being released periodically and ancient faults may be a likely place for this stress to be released. The relationship between ancient fault systems and the Tweed Shield Volcano has also been discussed and it is suggested here that the volcanic activity was associated with renewed faulting on the Great Moreton Fault System during the Cenozoic. The geomorphology and drainage patterns of southeast Queensland have been compared with expected morphological characteristics found at passive and other tectonic settings, both in Australia and globally. Of note are the comparisons with the East Brazilian Highlands, the Gulf of Mexico and the Blue Ridge Escarpment, for example. In conclusion, the results of the study clearly show that, although the region is described as a passive margin, its complex, past geological history and present compressive stress regime provide a more intricate and varied landscape than would be expected along typical passive continental margins. The literature review provides background to the subject and discusses previous work and methods, whilst the findings are presented in three peer-reviewed, published papers. The methods, hypotheses, suggestions and evidence are discussed at length in the final chapter.

New Approach on Robust Delay-Dependent H∞ Control for Uncertain T-S Fuzzy Systems With Interval Time-Varying Delay

This paper investigates the robust H∞ control for Takagi-Sugeno (T-S) fuzzy systems with interval time-varying delay. By employing a new and tighter integral inequality and constructing an appropriate type of Lyapunov functional, delay-dependent stability criteria are derived for the control problem. Because neither any model transformation nor free weighting matrices are employed in our theoretical derivation, the developed stability criteria significantly improve and simplify the existing stability conditions. Also, the maximum allowable upper delay bound and controller feedback gains can be obtained simultaneously from the developed approach by solving a constrained convex optimization problem. Numerical examples are given to demonstrate the effectiveness of the proposed methods.

Control and protection of a microgrid with converter interfaced micro sources

This paper describes protection and control of a microgrid with converter interfaced micro sources. The proposed protection and control scheme consider both grid connected and autonomous operation of the microgrid. A protection scheme, capable of detecting faults effectively in both grid connected and islanded operations is proposed. The main challenge of the protection, due to current limiting state of the converters is overcome by using admittance relays. The relays operate according to the inverse time characteristic based on measured admittance of the line. The proposed scheme isolates the fault from both sides, while downstream side of the microgrid operates in islanding condition. Moreover faults can be detected in autonomous operation. In grid connected mode distributed generators (DG) supply the rated power while in absence of the grid, DGs share the entire power requirement proportional to rating based on output voltage angle droop control. The protection scheme ensures minimum load shedding with isolating the faulted network and DG control provides a smooth islanding and resynchronization operation. The efficacy of coordinated control and protection scheme has been validated through simulation for various operating conditions.

Recombinant protein production using a Tobacco yellow dwarf virus-based episomal expression vector : control of Rep activity

Over the past decade, plants have been used as expression hosts for the production of pharmaceutically important and commercially valuable proteins. Plants offer many advantages over other expression systems such as lower production costs, rapid scale up of production, similar post-translational modification as animals and the low likelihood of contamination with animal pathogens, microbial toxins or oncogenic sequences. However, improving recombinant protein yield remains one of the greatest challenges to molecular farming. In-Plant Activation (InPAct) is a newly developed technology that offers activatable and high-level expression of heterologous proteins in plants. InPAct vectors contain the geminivirus cis elements essential for rolling circle replication (RCR) and are arranged such that the gene of interest is only expressed in the presence of the cognate viral replication-associated protein (Rep). The expression of Rep in planta may be controlled by a tissue-specific, developmentally regulated or chemically inducible promoter such that heterologous protein accumulation can be spatially and temporally controlled. One of the challenges for the successful exploitation of InPAct technology is the control of Rep expression as even very low levels of this protein can reduce transformation efficiency, cause abnormal phenotypes and premature activation of the InPAct vector in regenerated plants. Tight regulation over transgene expression is also essential if expressing cytotoxic products. Unfortunately, many tissue-specific and inducible promoters are unsuitable for controlling expression of Rep due to low basal activity in the absence of inducer or in tissues other than the target tissue. This PhD aimed to control Rep activity through the production of single chain variable fragments (scFvs) specific to the motif III of Tobacco yellow dwarf virus (TbYDV) Rep. Due to the important role played by the conserved motif III in the RCR, it was postulated that such scFvs can be used to neutralise the activity of the low amount of Rep expressed from a “leaky” inducible promoter, thus preventing activation of the TbYDV-based InPAct vector until intentional induction. Such scFvs could also offer the potential to confer partial or complete resistance to TbYDV, and possibly heterologous viruses as motif III is conserved between geminiviruses. Studies were first undertaken to determine the levels of TbYDV Rep and TbYDV replication-associated protein A (RepA) required for optimal transgene expression from a TbYDV-based InPAct vector. Transient assays in a non-regenerable Nicotiana tabacum (NT-1) cell line were undertaken using a TbYDV-based InPAct vector containing the uidA reporter gene (encoding GUS) in combination with TbYDV Rep and RepA under the control of promoters with high (CaMV 35S) or low (Banana bunchy top virus DNA-R, BT1) activity. The replication enhancer protein of Tomato leaf curl begomovirus (ToLCV), REn, was also used in some co-bombardment experiments to examine whether RepA could be substituted by a replication enhancer from another geminivirus genus. GUS expression was observed both quantitatively and qualitatively by fluorometric and histochemical assays, respectively. GUS expression from the TbYDV-based InPAct vector was found to be greater when Rep was expected to be expressed at low levels (BT1 promoter) rather than high levels (35S promoter). GUS expression was further enhanced when Rep and RepA were co-bombarded with a low ratio of Rep to RepA. Substituting TbYDV RepA with ToLCV REn also enhanced GUS expression but more importantly highest GUS expression was observed when cells were co-transformed with expression vectors directing low levels of Rep and high levels of RepA irrespective of the level of REn. In this case, GUS expression was approximately 74-fold higher than that from a non-replicating vector. The use of different terminators, namely CaMV 35S and Nos terminators, in InPAct vectors was found to influence GUS expression. In the presence of Rep, GUS expression was greater using pInPActGUS-Nos rather than pInPActGUS-35S. The only instance of GUS expression being greater from vectors containing the 35S terminator was when comparing expression from cells transformed with Rep, RepA and REnexpressing vectors and either non-replicating vectors, p35SGS-Nos or p35SGS-35S. This difference was most likely caused by an interaction of viral replication proteins with each other and the terminators. These results indicated that (i) the level of replication associated proteins is critical to high transgene expression, (ii) the choice of terminator within the InPAct vector may affect expression levels and (iii) very low levels of Rep can activate InPAct vectors hence controlling its activity is critical. Prior to generating recombinant scFvs, a recombinant TbYDV Rep was produced in E. coli to act as a control to enable the screening for Rep-specific antibodies. A bacterial expression vector was constructed to express recombinant TbYDV Rep with an Nterminal His-tag (N-His-Rep). Despite investigating several purification techniques including Ni-NTA, anion exchange, hydrophobic interaction and size exclusion chromatography, N-His-Rep could only be partially purified using a Ni-NTA column under native conditions. Although it was not certain that this recombinant N-His-Rep had the same conformation as the native TbYDV Rep and was functional, results from an electromobility shift assay (EMSA) showed that N-His-Rep was able to interact with the TbYDV LIR and was, therefore, possibly functional. Two hybridoma cell lines from mice, immunised with a synthetic peptide containing the TbYDV Rep motif III amino acid sequence, were generated by GenScript (USA). Monoclonal antibodies secreted by the two hybridoma cell lines were first screened against denatured N-His-Rep in Western analysis. After demonstrating their ability to bind N-His-Rep, two scFvs (scFv1 and scFv2) were generated using a PCR-based approach. Whereas the variable heavy chain (VH) from both cell lines could be amplified, only the variable light chain (VL) from cell line 2 was amplified. As a result, scFv1 contained VH and VL from cell line 1, whereas scFv2 contained VH from cell line 2 and VL from cell line 1. Both scFvs were first expressed in E. coli in order to evaluate their affinity to the recombinant TbYDV N-His-Rep. The preliminary results demonstrated that both scFvs were able to bind to the denatured N-His-Rep. However, EMSAs revealed that only scFv2 was able to bind to native N-His-Rep and prevent it from interacting with the TbYDV LIR. Each scFv was cloned into plant expression vectors and co-bombarded into NT-1 cells with the TbYDV-based InPAct GUS expression vector and pBT1-Rep to examine whether the scFvs could prevent Rep from mediating RCR. Although it was expected that the addition of the scFvs would result in decreased GUS expression, GUS expression was found to slightly increase. This increase was even more pronounced when the scFvs were targeted to the cell nucleus by the inclusion of the Simian virus 40 large T antigen (SV40) nuclear localisation signal (NLS). It was postulated that the scFvs were binding to a proportion of Rep, leaving a small amount available to mediate RCR. The outcomes of this project provide evidence that very high levels of recombinant protein can theoretically be expressed using InPAct vectors with judicious selection and control of viral replication proteins. However, the question of whether the scFvs generated in this project have sufficient affinity for TbYDV Rep to prevent its activity in a stably transformed plant remains unknown. It may be that other scFvs with different combinations of VH and VL may have greater affinity for TbYDV Rep. Such scFvs, when expressed at high levels in planta, might also confer resistance to TbYDV and possibly heterologous geminiviruses.

Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks—Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control.