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The Ratio of RyR2 and CSQ2 in Calcium Handling
No full textAtrial fibrillation (AF) is the most common arrhythmia of the heart, affecting 2-3% of the population. AF decreases the quality of life and increases the risk of mortality in patients. Although many patients see improvement with available treatments, a significant number do not. This necessitates further study into mechanisms of AF to elucidate new therapeutic targets. Many arrhythmias arise from the dysfunction of calcium handling within cardiomyocytes. The contraction of cardiomyocytes relies on the regulated release of calcium from the sarcoplasmic reticulum (SR), via the ryanodine receptor (RyR2). In many arrhythmias, RyR2 becomes “leaky” and spontaneously releases calcium in a process called store overload-induced calcium release (SOICR). This can lead to the development of delayed afterdepolarisations and trigger arrhythmic contractions. The function of RyR2 can be modulated by many accessory proteins, including calsequestrin 2 (CSQ2). CSQ2 primarily buffers Ca2+ within the SR, but can also influence RyR2’s propensity for SOICR. Both human and animal studies indicate a relative increase of RyR2, and/or a relative decrease of CSQ2 (increased RyR2:CSQ2) can result in an arrhythmic phenotype.
My project aimed to investigate the functional effects of changing RyR2:CSQ2 on the propensity for SOICR by co-expressing RyR2 and CSQ2 within HEK293 cells, by using fluorescently tagged RyR2 and CSQ2. HEK293 cells were loaded with a Ca2+-dye and underwent single-cell calcium imaging with increasing [Ca2+]¬O (0.1-1 mM) to determine the effect of changing RyR2:CSQ2 on the propensity for SOICR. The results of this show a biphasic effect of decreasing RyR2:CSQ2 on the propensity for SOICR, where high RyR2:CSQ2 cells had a higher frequency of SOICR events than the CSQ2-null cells (p=0.0326), and the medium RyR2:CSQ2 cells (p=0.0008), and low RyR2:CSQ2 cells (p<0.0001). These findings indicate that a high RyR2:CSQ2 ratio increases RyR2’s propensity for SOICR more than a complete loss of CSQ2. Despite this, my finding of decreased RyR2:CSQ2 being protective against SOICR also provides hope for future novel therapeutics that can restore the balance of expression between RyR2 and CSQ2
A Comparative Study of Electricity Demand Forecasting Models for Residential Hot Water at the Individual Household Level
No full textUnderstanding short term future electricity demand is necessary for maintaining a robust and efficient electricity grid. Research on electricity demand forecasting has traditionally ranged in scale from country-wide grid-level down to individual buildings. However, with emerging technologies allowing smart control of appliances, interest in forecasting the electricity demand of individual appliances is increasing. Smart control of appliances can improve energy efficiency and provide beneficial cost-reducing services to an electricity grid.
In New Zealand, electric hot water cylinders which are present in ~90% of households are currently controlled en-mass using ripple-control as part of centralised demand response programmes to reduce demand at peak times. Smart control of individual cylinders based on their forecasted demand could result in a larger reduction in demand with more nuanced control and less chance of households running out of hot water. This thesis compares a number of existing forecasting methods to the problem of forecasting the electricity demand of residential hot water cylinders at the individual household level. The forecasting models selected for analysis in this thesis were chosen based on their suitability according to existing literature, and preliminary exploratory analysis. A range of conventional forecasting models were assessed including autoregressive integrated moving averages (ARIMA), linear regression, and seasonal and trend decomposition with local polynomial regression (STL). In addition, one artificial intelligence model was assessed, namely support vector machines (SVM). A random walk model was included as a naive benchmark model for comparative purposes.
Existing one minute resolution household electricity demand data that was previously collected in the GREEN Grid study was used for forecasting model development. We selected 22 suitable households from this dataset where the demand of electric hot water cylinders was separately metered. Data was averaged over half-hour periods to mimic data currently available from smart meters in New Zealand. The hot water demand data from each household was separated chronologically into 'training' and 'validating' sets. Models were fitted to the training data and tested against the validating data to prevent inaccurate results from overfitting. The models were compared based on (i) forecast accuracy, (ii) computational speed of model fitting, (iii) interpretability, and (iv) ability to replicate underlying physical processes.
A relationship was discovered between the electricity demand of other appliances in the household and future hot water demand, which was incorporated into some models. SVM models were found to be the most accurate, with 16% lower errors than the naive model, however they performed very poorly in other metrics. The most complex conventional model incorporated STL with ARIMA while including other electricity demand as an external regressor. This performed almost as well as the SVM models in accuracy, while also performing reasonably well in other metrics, and based on the analysis in this thesis, would be the recommended model for use in smart control
Materialising Ancestral Madang: Pottery Production and Subsistence Trading on the Northeast Coast of New Guinea
No full textMaterialising Ancestral Madang documents the emergence of pottery production processes and exchange networks along the northeast coast of New Guinea during the last millennium before the present. This dynamic period in the Pacific’s human past involved important fluctuations to people’s mobility, social interaction, and technological organisation. It therefore remains crucial to understanding and historicising the expansive maritime subsistence trading networks that famously characterised the coast in the late 19th and early 20th centuries. This book investigates these transformations by exploring the archaeology of Madang District; the heart of the Madang exchange network that revolved around the production and distribution of distinctive red-slipped pots. Potsherds of this style have been previously found spanning a 200 km radius, reaching Karkar Island, the Bismarck Archipelago, and even the New Guinea Highlands. By combining archaeological survey, excavation, craft ethnography, and archaeometric analyses, the volume systematically delineates the production groups that were working within this broader community of practice. The study shows that pre-colonial potters made use of a range of local raw materials and were free to improvise with their forming and decorating techniques but learned and reproduced similar technological sequences over the past 500–600 years. It is likely that social restrictions permitted only potters from a small number of clans to produce ceramics and that the finished vessels were then distributed both informally within the local area and strategically during extensive trade voyages along the northeast coast of New Guinea. These results therefore cast light on an important but previously obscured aspect of Pacific culture history and provide a model for how craft production and exchange processes have manifested and commodified across the generations.Peer Reviewe
New Business Models for Legal Services
No full textThis working paper outlines possible innovations to legal services, drawing on examples of new models developing both here and abroad
Optimal coalition structure generation on large-scale renewable energy smart grids
No full textMost renewable energy sources are dependent on unpredictable weather conditions, which have considerable variation over space and time. The intermittent nature of this production means that any renewable energy prosumer may sometimes produce an amount of energy in excess of its local consumption needs and sometimes in deficiency. This thesis is concerned with developing methods that can improve the effectiveness and widespread adoption of renewable energy usage. In order for renewable energy to be more economically viable, there needs to be a scheme for sharing energy among the prosumers so that those with excess energy can give their excess amounts to those in energy deficiency. That is the task addressed in this thesis.
The way to deal with this problem is to setup an optimal arrangement of local coalitions of renewable energy prosumers such that energy is shared within the coalitions in an optimally efficient manner. As is formally explained early on in this work, finding such an optimal coalition arrangement is an example of a Coalition Structure Generation (CSG) problem. The most straightforward way to find an optimal solution for a given pool of prosumer agents in these circumstances is to examine every possible coalition partition (coalition structure) and evaluate its comparative utility. This is known as ``exhaustive search'' (ES) and can be computationally expensive. As has been shown earlier, the number of such evaluations in ES even for a pool of twenty agents can be in the tens of trillions.
The problem for us in the renewable energy domain is that, because of the constantly changing weather conditions among the scattered prosumers, the CSG optimization calculation must be carried out every hour of the day. This means that the ES approach in the CSG optimization calculation for a reasonable number of prosumer agents is computationally intractable. So a more computationally feasible stochastic optimization method must be used, which searches through the coalition structure search space in order to find a reasonably good solution even if it is not the global optimum.
To this end, a number of stochastic optimization search methods have been investigated in this thesis, including some of our own novel extensions to existing approaches. These search methods have been examined with respect to two different connection arrangements with respect to the outside world – (1) when the local prosumer networks have a connection to a public utility power grid and can therefore buy needed energy (at a high price) from the grid and sell excess energy (at a low price) to the grid and (2) when the local prosumer networks are isolated from any public utility, which is referred to as ``island mode''. The overall goal of these investigations has been to find an optimization approach that arrives at a near-optimal (near the global optimum of the given search space) that is computationally efficient (i.e. it does not require a vast amount of computer memory or running time).
Based on these empirical examinations, which have employed realistic parameters drawn from existing consumption and renewable energy data sets, the following conclusions concerning renewable energy can be drawn from this study:
• It is feasible to employ ordinary computer resources to obtain on an
hourly basis near-optimal energy-sharing coalition structures that will
lead to the more effective and economical use of renewable energy.
• This energy-sharing approach will contribute to more rapid adoption
and proliferation of existing renewable energy equipment and
infrastructure.
The principal contributions towards these end that this thesis work has
made are as follows:
• A modelling framework has been set up that can be used for extensive
empirical determinations of near-optimal energy-sharing coalition
structures.
• A detailed empirical study has been carried out that has examined the
relative capabilities in this context of various optimal coalition structure
search methods, including genetic algorithms (GA), dynamic
programming (DP), particle swarm optimization (PSO), population-based
incremental learning (PBIL), and several variants to PBIL.
• The novel extensions to basic PBIL optimization have included Top-k
Merit Weighting PBIL (PBIL-MW), Set-ID Encoding Schemes, and
Hierarchical PBIL-MW
Clinical anatomy of the neurofascial sheath
No full textBackground: The peripheral nerve blockade (PNB) and minimally invasive surgery are central to the “Fast Track Surgery” strategy which uses multimodal perioperative rehabilitation programs and aims to facilitate early discharge from the hospital and more rapid resumption of normal activities of daily living after surgery. The anatomical basis for the PNB is one that conceives of the nerve to be enclosed by a tubular fascial sheath, called the neurofascial sheath (NFS), into which the local anaesthetic (LA) solution is injected. The confinement of the LA in the NFS can prolong the effective time of anaesthetic and reduce drug dosage and complications. However, in the literature, the anaesthetic effects of the intra-NFS injection vary significantly and have shown significant regional variations.
The NFS is composed of the endoneurium, perineurium, epineurium and extraneural fascia, from innermost to outermost, respectively. It has been suggested that during the PNB, the optimal needle placement is in a potential space between the extraneural fascia and the epineurium. An intraneural injection is defined as the needle tip penetrates the epineurium. The intraneural injection may damage the nerve and thus is not recommended. However, some studies argue that the intraneural injection may not cause nerve injury but help to more precisely localise the injected LA. This debate is mainly because the origin and architecture of the NFS and its anatomical relationship among its sublayers and with the neighbouring structures remain unclear. For example, it is generally believed that the perineurium extends from the meninges of the brain or spinal cord and serves as the blood-nerve barrier to protect the axons from mechanical and chemical attacks. However, some recent studies found that both arachnoid and dura maters (parts of the meninges) do not extend beyond the skull base or vertebrae in the human, suggesting that the NFS may have different origins, particularly for the distal segment of a peripheral nerve. Several questions remain to be clarified. Does an intact NFS exist along a peripheral nerve? Where do the different sublayers of the NFS originate? Does the architecture of the NFS vary at different locations? What is the anatomical relationship between the NFS and its neighbouring structures? Therefore, the central hypothesis of this thesis is that the NFS of a peripheral nerve has a consistent fibrous configuration along its whole course.
Objectives: The overall aim of this thesis is to identify the origin and configuration of the NFS of various peripheral nerves. The specific objectives are to investigate the origin and configuration of the NFS of (1) the distal segment of the spinal nerve, (2) the proximal segment of the spinal nerve, and (3) the proximal (intracranial) segment of the cranial nerve.
Material and Methods: A total of 80 cadavers (39 females, 41 males; age range, 38-97 years) were used in this thesis. The coloured latex injection, micro-dissection, epoxy sheet plastination, confocal microscopy, 3-dimensional reconstruction methods were applied in the cadaveric studies. For Objective 1, a total of 64 volunteers and 45 patients were included in the observation and measurement of the femoral nerve and lateral femoral cutaneous nerve (LFCN), and the ultrasound-guided fascia iliac compartment block (FICB) or the femoral nerve block. The studies of this thesis were performed in accord with the institutional ethical guidelines and approved by the Human Research Ethics Committee of the University of Otago for the cadaver study only, the Medical Ethics Committee of Anhui Medical University and the Committee on Medical Ethics of the First Affiliated Hospital of Anhui Medical University, China, for both cadaver and living subject studies.
Results and discussion:
Objective 1: The origin and configuration of the NFS of the femoral nerve and the LFCN were defined in the pelvis and upper thigh regions. In the pelvis, the fascia iliaca was originated from the peripheral fascicular aponeurotic sheet of the iliopsoas. The fascia iliaca compartment was a funnel-shaped adipose space between the fascia iliaca and the epimysium of the iliopsoas, had a superior and an inferior opening and contained the femoral nerve and the LFCN but not obturator nerve. In the upper thigh, the fascial lata was originated from the prolongation of the inguinal ligament and the newly identified “iliolata ligaments”. The fascia iliaca and the aponeurotic fibres of the transversus abdominis and the internal oblique abdominis formed a conjoint tendinous sheet under the inguinal ligament. The LFCN pierced the conjoint tendinous sheet and entered into an adipose compartment which was sandwiched in between the fascia lata and the epimysium of the sartorius muscle and then a ligamental canal which was formed by the iliolata ligaments. All these structures were detectable under ultrasound scanning in healthy volunteers. These findings endorse the classical FICB and indicate that the conjoint tendinous sheet can be used as a key ultrasound landmark for the ultrasound-guided FICB. The conjoint tendinous sheet and the ligamental canal of the iliolata ligaments are two major sites susceptible to the entrapment of the LFCN. Based on the fibrous origin and configuration of the NFS, the conjoint tendinous sheet, the sartorius muscle and the anterior superior iliac spine are recommended as the anatomical landmarks to identify and visualise the LFCN with ultrasound and a theoretical strategy for decompression of the LFCN is proposed.
Objective 2: The origin and configuration of the NFS of the proximal segment of the spinal nerve were revealed in the lumbar intervertebral foramina (IVF). The boundaries (particularly the lateral and medial boundaries) and subdivisions of the lumbar IVF were precisely defined. The inferior border of the upper pedicle and the dorsal root ganglion were used to subdivide the lumbar IVF into the supermedial extension, the superior compartment and the inferior compartment. The configuration and localisation of the neurovascular and adipose zones were different between the upper (IVFs L1-2 & L2-3) and lower (IVFs L3-4 & L4-5) lumbar spines. In the upper lumbar spine, the superomedial extension was occupied by the nerve roots and vessels within a dural sleeve and the venous plexus with sparse adipose tissue. The superior compartment was occupied by the nerve roots, dorsal root ganglion, vessels and adipose tissue. The inferior compartment contained a small anteroinferior adipose pocket and a large posterosuperior neurovascular zone and the venous plexus. In the lower lumbar spine, the adipose tissue almost entirely occupied the inferior compartment, and the neurovascular structures were limited within the superior compartment. The adipose zone was gradually tapered and rotated from the inferior compartment to the medial part of the superior compartment and further to the superomedial extension. The findings highlight differences of the fine 3D architecture of the NFS of the proximal spinal nerve and its relationship with surrounding vascular and adipose tissue between the upper and lower lumbar IVFs. The findings may contribute to optimise the surgical approaches through the IVF at different lumbar spinal levels and help to shorten the learning curve of the transforaminal operative techniques.
Objective 3: The origin and configuration of the NFS of the proximal (intracranial) segment of the trigeminal nerve (TN) and its relationship with Meckel’s cave (MC) were studied. The results showed: (1) the trigeminal ganglion was sandwiched in between the arachnoid and dural walls of MC, (2) the rootlets and divisions of the TN were enclosed in the centrally reflected arachnoid sleeves and the peripheral dural sheaths, respectively, and the peripheral dural sheath contributed to the epineurium and perineurium of the division but extended only up to the level of the extracranial exit of the nerves, and (3) the dural wall of MC originated from the meningeal dura and appeared as a half-crescent shape with a wide superficial-lateral edge and a thin deep-medial edge which merges with the endosteal dura of the middle cranial fossa. These findings reveal the fine architecture of the NFS of the TN and its relationship with MC and will contribute to a better understanding of the nature and growth pattern of the TN tumour, and may provide guidance on the precise surgical approach to TN in the future.
Conclusions: The findings of this study disagree with the central hypothesis of this thesis that the NFS of a peripheral nerve has a consistent fibrous configuration along its whole course. The origin and fibrous configuration of the NFS of a peripheral nerve vary in a region-dependent pattern. The results of this study will not only help to optimise PNB techniques, but also provide a better understanding of the minimally invasive surgical approach and the perineurial tumour spread pathway. The results also indicate that for any given peripheral nerve, the NFS of its different segments should be studied specifically in a region-dependent manner
Waitangi Tribunal evidence brief (WAI2915): explaining and responding to causes of Māori disparities in the child protection system
No full textThis invited brief responds to the three inquiry questions:
(a) Why has there been such a significant and consistent disparity between the number of tamariki Māori and non- Māori children being taken into state care under the auspices of Oranga Tamariki and its predecessors?
(b) To what extent will the legislative policy and practice changes introduced since 2017, and currently being implemented, change this disparity for the better?
(c) What (if any) additional changes to Crown legislation, policy or practice might be required in order to secure outcomes consistent with Te Tiriti/the Treaty and its principles?
In response to these questions, our brief describes and explains disparities and their intersectional nature; discusses the interaction of risk and multiple bias types; comments on if the 2017 changes will be sufficient to address them; and explains how one iwi-Oranga Tamariki partnership is currently operating. Suggestions to improve devolution and procedural fairness in decision-making are discussed
Cultural traditions and sustainable rural livelihoods : a case study from the Kandyan villages, central Sri Lanka
No full textConsiderable attention has been directed recently towards the role of culture and traditional values in the sustainable well-being of rural communities. Development scholars seem to have accepted that cultural attributes and values actually matter in development, but there is still much debate over 'how', 'why' and 'where' they matter.
This thesis explores the significance of cultural traditions and the roles they play in the context of attaining sustainable rural livelihoods. The hegemony of 'Western values' is contested and the need for greater appreciation of 'other', non-Western values and traditions is emphasised. The research specifically explores how cultural traditions can support a livelihood perspective in pragmatic and more effective ways, whereby tangible and intangible aspects of culture and traditional values can be explicitly treated as an important resource, namely 'cultural capital' .
Drawing upon evidence from field-based research in five craft-working villages in the Kandy region of central Sri Lanka, the study shows how culture and traditional values play a significant role in influencing livelihood choices, asset ownership, livelihood resilience and sustainability. The study utilises qualitative research methods with participatory techniques to evaluate 'how' people recognise and interpret their culture and traditional values, and 'what' specific roles these play in contributing to sustainable livelihood systems. It is suggested that the evaluation of livelihood assets through a cultural perspective provides a valuable and nuanced understanding of a community's genuine strengths and resource endowments and how these are, or might be, converted into livelihood outcomes .
In addition to contributing to academic research and development planning in Sri Lanka, the thesis has wider relevance for development studies and livelihood analysis, and proposes future strategies for incorporating culture more effectively into development interventions which might hopefully lead to sustainable livelihoods
The nature and origin of gold mineralization at Sams Creek, north-west Nelson
No full textGold mineralization is hosted by a peralkaline granite dyke which outcrops over about eight kilometers in the area of Sams Creek, a tributary of the Takaka River, north-west Nelson. The granite is riebeckite and acmite bearing, with antiperthitic alkali feldspars; it has A-type chemistry, implying an origin by partial melting at a temperature > 800°C. Associated with the granite is a suite of lamprophyre dykes; now highly altered, they probably range from original camptonites to quartz - bearing calc-alkaline types. A quartz- bearing lamprophyre has intruded along the footwall contact of the granite over much of the observed outcrop length; it may have been a source rock for gold. Granite intrusion is inferred to have occurred before or during the 0 2 deformation in the surrounding shales and quartzites, suggesting a minimum age of 400Ma. Deformation involving E-W compression has caused the granite to break into essentially rigid pieces, of the order of 50m in size, surrounded by ductilely deforming sediments. Strain has been concentrated into the footwall lamprophyre, which has also served as a conduit for hydrothermal fluids. Locally, small brittle - ductile shear zones occur within the granite; some of them post - date the mineralization. Tectonic imbrication of the granite and the development of fracture permeability have probably controlled the locus of gold mineralization.
Two styles of hydrothermal alteration are observed: in Main Zone, hydrolysis of riebeckite produced the assemblage magnetite+ siderite; an influx of Fe, As, S and associated Au then produced the assemblage quartz + albite + K-feldspar + pyrite + arsenopyrite. Gold is present as the native element, poikilitically enclosed by arsenopyrite. In the western part of the area, iron has been lost during the early stages of alteration to produce the assemblage quartz - albite - K-feldspar; with further reaction, feldspars alter to sericite, and pyrite and arsenopyrite are deposited. Gold values are lower than in Main Zone. The mineralizing fluids are inferred to have been metamorphic in origin. Geothermometry based on the assemblage arsenopyrite - pyrite - sphalerite suggests a temperature of 370 ±50 °C for Main Zone. Fluid inclusions in the western part of the area show evidence of immiscibility between H2O and CO2; their homogenization temperature directly yields an estimate of 260 ± 25°C for the hydrothermal fluid. Water-bearing inclusions from Main Zone, taken in conjunction with the arsenopyrite – sphalerite geothermometer, suggest a pressure of between one and two kilobars for the mineralization. In Main Zone, progressive hydrolysis of granite was accompanied by falling aO2 , which resulted in the precipitation of arsenopyrite; this in turn caused a localized fall in total. dissolved sulphur which caused gold to co-precipitate. The fluid pH was ~ 9. Further west, in the sericitically altered zone, the fluid pH was buffered to between 5 and 5.4 by the alteration of K-feldspar to sericite. The lower pH has been critical in limiting gold mineralization in the western part of the area
The colours of that place: setting and memory in Irish short fiction
No full textThis creative-practice thesis explores the interplay of memory and setting in the short fiction of Colum McCann, with a view to illuminating my own collection of short stories.
In Chapter one I have chosen four fundamental aspects and two functions of setting to analyse how McCann uses setting to evoke memory in his first short story collection Fishing the Sloe-Black River.
The ways in which McCann experiments with narrative time to create diverse settings in his novella ‘Thirteen Ways of Looking,’ are the focus of Chapter two. In that chapter I argue that McCann’s use of homodiegetic and heterodiegetic narration provides an inventive means to depict character experience and memory. Given McCann’s recurring references to memory, I assert that his novella can be defined as a ‘fiction of memory.’ I also explore the role of figurative language in McCann’s evocation of memory in relation to setting, and illustrate how the epigraphic inclusion of Wallace Stevens’ ‘Thirteen Ways of Looking at a Blackbird’ affects the narrative content of the novella.
In Chapter three I examine the function of the exegesis in creative practice research, which is followed by an exploration of the parallels between the critical theories of T.S Eliot, Harold Bloom, Gérard Genette and Mikhail Bakhtin. I then offer a commentary on my creative process, and discuss my novella Dear Billie, in relation to McCann’s novella Thirteen Ways of Looking, and the hypertextual connections of my short story ‘Falling Softly, Softly Falling’ in juxtaposition with James Joyce’s ‘The Sisters’ and McCann’s ‘Sisters.’
Chapter four summarises the discoveries of my critical and creative research by looking at how the methodological approach of ‘bricolage’ informed my knowledge as a creative practitioner and researcher. Finally, it reflects on creative-practice researcher Bradley Haseman’s appeal for the recognition of performative research to be considered as a research outcome in its own right. Therefore, in Chapter five I consider the outcome of my creative component to be my collection Nothing to Say I was Here, which, like McCann’s Thirteen Ways of Looking, comprises a novella and three short stories.
By assuming a creative-practice research approach, it is my intention to offer a writerly interpretation of McCann’s short fiction in order to demonstrate the interconnection of memory and setting, and finally, to explore how this has enriched my own creative process