Passage shaping in Axial Flow Turbines

This thesis describes the novel combination of reverse compound lean, leading edge extension and non-axisymmetric endwall profiling in a highly loaded turbine geometry, for the reduction of secondary flow and loss. The thesis describes each geometrical modification in turn (in addition to their combination) and details their development from concept to experimentally measured performance. The designs are assessed using 3D Navier Stokes modelling. The best performing designs were manufactured and tested experimentally using pneumatic probes, flow visualisation and static pressure tappings. The key sections of the thesis include: • A review of previous non-axisymmetric profiled endwalls, with a view to understanding their performance in a full 3D passage design • The assessment of reverse compound lean in a highly loaded turbine cascade • The design development and subsequent testing of a 3D turbine passage design for minimising pressure loss associated with and kinetic energy in secondary flows. In summary, Passage Shaping works by using reverse compound lean to draw the secondary flows in to the endwall, where a combination of leading edge extension and non-axisymmetric endwall profiling work on the secondary flows to reduce their intensity. The key changes in the downstream flowfield, as a result of the passage shaping designs, are a reduction in loss (both profile and secondary) and a reduction in secondary flow, resulting in a more uniform exit yaw angl

Role of the ipsilateral primary motor cortex in the visuo-motor network during fine contractions and accurate performance

It is widely recognized that continuous sensory feedback plays a crucial role in accurate motor control in everyday life. Feedback information is used to adapt force output and to correct errors. While primary motor cortex contralateral to the movement (cM1) plays a dominant role in this control, converging evidence supports the idea that ipsilateral primary motor cortex (iM1) also directly contributes to hand and finger movements. Similarly, when visual feedback is available, primary visual cortex (V1) and its interactions with the motor network also become important for accurate motor performance. To elucidate this issue, we performed and integrated behavioral and electroencephalography (EEG) measurements during isometric compression of a compliant rubber bulb, at 10% and 30% of maximum voluntary contraction, both with and without visual feedback. We used a semi-blind approach (functional source separation (FSS)) to identify separate functional sources of mu-frequency (8-13Hz) EEG responses in cM1, iM1 and V1. Here for the first time, we have used orthogonal FSS to extract multiple sources, by using the same functional constraint, providing the ability to extract different sources that oscillate in the same frequency range but that have different topographic distributions. We analyzed the single-trial timecourses of mu power event-related desynchronization (ERD) in these sources and linked them with force measurements to understand which aspects are most important for good task performance. Whilst the amplitude of mu power was not related to contraction force in any of the sources, it was able to provide information on performance quality. We observed stronger ERDs in both contralateral and ipsilateral motor sources during trials where contraction force was most consistently maintained. This effect was most prominent in the ipsilateral source, suggesting the importance of iM1 to accurate performance. This ERD effect was sustained throughout the duration of visual feedback trials, but only present at the start of no feedback trials, consistent with more variable performance in the absence of feedback. Overall, we found that the behavior of the ERD in iM1 was the most informative aspect concerning the accuracy of the contraction performance, and the ability to maintain a steady level of contraction. This new approach of using FSS to extract multiple orthogonal sources provides the ability to investigate both contralateral and ipsilateral nodes of the motor network without the need for additional information (e.g. electromyography). The enhanced signal-to-noise ratio provided by FSS opens the possibility of extracting complex EEG features on an individual trial basis, which is crucial for a more nuanced understanding of fine motor performance, as well as for applications in brain-computer interfacing

Brain state dynamics differ between eyes open and eyes closed rest

The human brain exhibits spatio-temporally complex activity even in the absence of external stimuli, cycling through recurring patterns of activity known as brain states. Thus far, brain state analysis has primarily been restricted to unimodal neuroimaging data sets, resulting in a limited definition of state and a poor understanding of the spatial and temporal relationships between states identified from different modalities. Here, we applied hidden Markov model (HMM) to concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI) eyes open (EO) and eyes closed (EC) resting-state data, training models on the EEG and fMRI data separately, and evaluated the models' ability to distinguish dynamics between the two rest conditions. Additionally, we employed a general linear model approach to identify the BOLD correlates of the EEG-defined states to investigate whether the fMRI data could be used to improve the spatial definition of the EEG states. Finally, we performed a sliding window-based analysis on the state time courses to identify slower changes in the temporal dynamics, and then correlated these time courses across modalities. We found that both models could identify expected changes during EC rest compared to EO rest, with the fMRI model identifying changes in the activity and functional connectivity of visual and attention resting-state networks, while the EEG model correctly identified the canonical increase in alpha upon eye closure. In addition, by using the fMRI data, it was possible to infer the spatial properties of the EEG states, resulting in BOLD correlation maps resembling canonical alpha-BOLD correlations. Finally, the sliding window analysis revealed unique fractional occupancy dynamics for states from both models, with a selection of states showing strong temporal correlations across modalities. Overall, this study highlights the efficacy of using HMMs for brain state analysis, confirms that multimodal data can be used to provide more in-depth definitions of state and demonstrates that states defined across different modalities show similar temporal dynamics.</p

Resetting the late timing of ‘night owls’ has a positive impact on mental health and performance

Background There is conflict between living according to our endogenous biological rhythms and our external environment, with disruptions resulting in negative consequences to health and performance. This is often documented in shift work and jet lag, but ‘societal norms’ (eg, typical working hours) can create profound issues for ‘night owls’, people whose internal biological timing predisposes them to follow an unusually late sleep-wake cycle. Night owls have also been associated with health issues, mood disturbances, poorer performance and increased mortality rates. Methods This study used a randomized control trial design aimed to shift the late timing of night owls to an earlier time (phase advance), using non-pharmacological, practical interventions in a real-world setting. These interventions targeted light exposure (through earlier wake up/sleep times), fixed meals times, caffeine intake and exercise. Results Overall, participants demonstrated a significant advance of ~2 h in sleep/wake timings as measured by actigraphy and circadian phase markers (dim light melatonin onset and peak time of the cortisol awakening response), whilst having no adverse effect on sleep duration. Notably, the phase advance was accompanied by significant improvements to self-reported depression and stress, as well as improved cognitive (reaction time) and physical (grip strength) performance measures during the typical 'suboptimal morning hours. Conclusions Our findings propose a novel strategy for shifting clock timing towards a pattern that is more aligned to societal demands that could significantly improve elements of performance, mental health and sleep timing in the real world.</p

An Investigation of Links Between Simple Sequences and Meiotic Recombination Hotspots

Previous evidence has shown that the simple sequences microsatellites and poly-purine/poly-pyrimidine tracts (PPTs) could be both a cause, and an effect, of meiotic recombination. The causal link between simple sequences and recombination has not been much explored, however, probably because other evidence has cast doubt on its generality, though this evidence has never been conclusive. Several questions have remained unanswered in the literature, and I have addressed aspects of three of them in my thesis. First, what is the scale and magnitude of the association between simple sequences and recombination? I found that microsatellites and PPTs are strongly associated with meiotic double-strand break (DSB) hotspots in yeast, and that PPTs are generally more common in human recombination hotspots, particularly in close proximity to hotspot central regions, in which recombination events are markedly more frequent. I also showed that these associations can't be explained by coincidental mutual associations between simple sequences, recombination and other factors previously shown to correlate with both. A second question not conclusively answered in the literature is whether simple sequences, or their high levels of polymorphism, are an effect of recombination. I used three methods to address this question. Firstly, I investigated the distributions of two-copy tandem repeats and short PPTs in relation to yeast DSB hotspots in order to look for evidence of an involvement of recombination in simple sequence formation. I found no significant associations. Secondly, I compared the fraction of simple sequences containing polymorphic sites between human recombination hotspots and coldspots. The third method I used was generalized linear model analysis, with which I investigated the correlation between simple sequence variation and recombination rate, and the influence on the correlation of additional factors with potential relevance including GC-content and gene density. Both the direct comparison and correlation methods showed a very weak and inconsistent effect of recombination on simple sequence polymorphism in the human genome.Whether simple sequences are an important cause of recombination events is a third question that has received relatively little previous attention, and I have explored one aspect of it. Simple sequences of the types I studied have previously been shown to form non-B-DNA structures, which can be recombinagenic in model systems. Using a previously described sodium bisulphite modification assay, I tested for the presence of these structures in sequences amplified from the central regions of hotspots and cloned into supercoiled plasmids. I found significantly higher sensitivity to sodium bisulphite in humans in than in chimpanzees in three out of six genomic regions in which there is a hotspot in humans but none in chimpanzees. In the DNA2 hotspot, this correlated with a clear difference in numbers of molecules showing long contiguous strings of converted cytosines, which are present in previously described intramolecular quadruplex and triplex structures. Two out of the five other hotspots tested show evidence for secondary structure comparable to a known intramolecular triplex, though with similar patterns in humans and chimpanzees. In conclusion, my results clearly motivate further investigation of a functional link between simple sequences and meiotic recombination, including the putative role of non-B-DNA structures

The contribution of sleep and co-occurring neurodevelopmental conditions to quality of life in children with epilepsy

BACKGROUND: Health-related quality of life (HRQOL) in children with epilepsy (CWE) is multifactorial and can be affected not only by epilepsy-specific variables but also co-occurring conditions such as sleep disturbances, autism, and attention deficit hyperactivity disorder (ADHD). While highly prevalent in CWE, these conditions are underdiagnosed despite having a significant impact on HRQOL. Sleep problems have a complex relationship with epilepsy and neurodevelopmental characteristics. However, little is known about how these issues interact and contribute to HRQOL. OBJECTIVES: The current study aims to explore the relationship between sleep and neurodevelopmental characteristics on HRQOL in CWE. METHODS: 36 CWE aged 4-16 years old were recruited from two hospitals and asked to wear an actiwatch for a period of 14 days and caregivers completed a series of questionnaires assessing co-occurrences and epilepsy-specific variables. RESULTS: A high proportion of CWE (78.13%) presented significant sleep problems. Informant-reported sleep problems were significantly predictive of HRQOL above seizure severity and the number of antiseizure medications. Interestingly, informant-reported sleep problems were no longer significantly predictive of HRQOL when neurodevelopmental characteristics were considered, indicating a possible mediating effect. Similarly, actigraphy-defined sleep (variability in sleep onset latency) displayed a similar effect but only for ADHD characteristics, whereas autistic characteristics and variability in sleep onset latency continued to exert an individual effect on HRQOL. CONCLUSION: These data from our study shed light on the complicated relationship between sleep, neurodevelopmental characteristics and epilepsy. Findings suggest that the impact of sleep on HRQOL in CWE is possibly mediated by neurodevelopmental characteristics. Furthermore, the impact this triangular relationship exerts on HRQOL is dependent on the type of tool used to measure sleep. These findings highlight the importance of a multidisciplinary approach to epilepsy management