Enabling Ableton : facilitating music technology in secondary music education through Discholars : an exegesis presented in partial fulfilment of the requirements of the degree of Master of Creative Enterprise at Massey University, Wellington, New Zealand

Discholars is a company designed to enhance and modernise music education in New Zealand by offering tuition in digital and electronic instruments. It was founded in response to the ubiquity of music technology in the music industry and the opportunity that provides for music education. The creative focus of this research has been to build a curriculum to teach music using a digital audio workstation (DAW) as the primary instrument. Through a series of structured lesson plans, this curriculum teaches musical concepts and production techniques. It incorporates modern research in music pedagogy and is designed to align with the New Zealand curriculum. Discholars' mission is to empower students to express themselves musically as a result of music technology tuition

Hydrogen storage and fuel processing strategies

PhD ThesisIt is widely recognised that fossil fuels are finite, and alternatives should be investigated to secure future energy supplies. Much research is directed towards hydrogen as a fuel, but the gas is unmanageable without an effective storage and distribution strategy. This work investigates the Methylcyclohexane-Toluene-Hydrogen (MTH) system of hydrogen storage with a view to providing vehicular fuel or storing energy produced by intermittent producers. Stable liquid-hydrocarbon hydrogen storage enables hydrogen distribution using the existing fossil fuel network, eliminating the need to build a new fuel infrastructure. A literature survey is carried out covering the area of Liquid Organic Hydrogen Carriers (LOHCs). A study of the technoeconomic bottlenecks which would prevent the widespread use of the MTH system is conducted to direct the project research efforts, which reveals that the vehicular on-board dehydrogenation system must be reduced in size to be practical. Process intensification is attempted by dehydrogenating methylcyclohexane in the liquid-phase, which is experimentally demonstrated in this work (an original contribution). However, to be feasible for a vehicle, the liquid-phase dehydrogenation system demands a specific window of conditions, with hydrocarbon vapour pressure, enthalpy of reaction and equilibrium constant all being important factors. No window is possible to satisfy all conditions for the MTH system, which renders this vehicular system infeasible. Alternative liquid carriers are investigated to solve the problem, but no clear candidate carrier is found without using highly experimental and costly molecules. This leads to a new investigation of other applications for the MTH system. MCH for power to a Scottish whisky distillery is investigated, followed by an investment appraisal of the distillery system. The system is technically feasible but attracts a high capital expenditure (almost £16M) and operational cost (£2.4M annually) which is uncompetitive with alternative options such as biomass fuels. Finally, possible future work in the field of LOHC technology is considered.Chemistry Innovation KTN

Time to quit? Non-genetic heterogeneity in cell fate propensity after DNA damage

Cellular checkpoints are typically considered to both facilitate the ordered execution of the cell cycle and to act as a barrier to oncogene driven cell cycles and the transmission of unresolved genetic lesions from one phase to the next. Furthermore, these mechanisms are also believed to underpin the responses of cells, both in normal and cancerous tissues, to those therapies that either directly or indirectly generate DNA damage. In recent studies however, it has become clear these checkpoints permit the passage of significant genomic aberrations into subsequent cell cycle phases and even descendant cells, and that heterogeneous responses are apparent amongst genetically identical cells. The consequences of this checkpoint ‘negligence’ remain relatively uncharacterised despite the importance of checkpoints in current models for how genomic instability is avoided in the face of ubiquitous DNA damage. Unresolved DNA damage is presumably inherited by subsequent cell cycle phases and descendant cells yet characterisation of the consequences of this has been relatively limited to date. I therefore utilised microscopy-based lineage tracing of cells expressing genetically encoded fluorescent sensors, particularly the Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) probes (Sakaue-Sawano et al., 2008), with semi-automated image analysis to characterise the response of single cells and their descendants to DNA lesions across multiple cell cycle generations. This approach, complemented by generational tracing by flow cytometry, permitted me to characterise the timing of cell fate determination in treated and descendant cells, the non-genetic heterogeneity in checkpoint responses and overall lineage behaviour, correlations between cells (similarly to Sandler et al., 2015) and cell cycle timing dependencies in the response to DNA damaging agents. With these single cell analytical approaches I show that the consequences of DNA damage on descendant cell fate is dramatic, suggesting checkpoint mechanisms may have consequences and even cooperate across phases and generations. U2OS cell lineages traced for three generations following the induction of DNA damage in the form of strand breaks showed greatly induced cell death in the daughters and granddaughters of DNA damaged cells, termed delayed death. Furthermore, lineage behaviour was characterised as highly heterogeneous in when and whether cell death occurred. Complementary flow cytometric approaches validated the findings in U2OS cells and suggested HeLa cells may show similar behaviour. These findings indicate that checkpoint models need to incorporate multigenerational behaviour in order to better describe the response of cells to DNA damage. Understanding the processes governing cell fate determination in descendant cells will impact upon our understanding of the development of genomic instability during carcinogenesis and how DNA-damaging chemotherapeutics drive cells to ‘quit’ the cell cycle.Cambridge Cancer Centr

Scour-Resilient Bio-Inspired Geomorphic Designs: the Male Japanese Puffer Fish Nest

In 1995, divers noticed a strange circular pattern on the seabed off Japan. The geometric formations mysteriously appeared and dissolved, and no-one knew what made them. Finally, the creator of these remarkable formations was found: a new species of pufferfish from the genus Torquigener. The male puffer fish executes a design of mathematical perfection in the form of ornate circles. As he swims along the seabed, he laboriously flaps his fins and rearranges the sand, creating the geomorphic feature dubbed crop circle by the pioneers who first noticed them. The significance to understand the puffer fish design is magnified when we consider that the nest is able to maintain its morphological features for long periods even though it is built entirely of mobile particles in an area where the flow does not stop. As a relatively new discovery, the exact reasons behind why the pufferfish spends such a long time constructing and cultivating the nest it still a question that is shrouded in a substantial amount of mystery. Male puffer fish spend many days caring for the eggs, the only puffer fish genus to be overserved doing so; suggesting that Torquigener place an unusually large emphasis on ensuring the survival of their eggs. It is hypothesised that the nest is created as a mating display, as female puffer fish will visit the site, presumably assessing various characteristics of the nest. It is not known exactly what parameters the females judge the nest on; whether it be size, symmetric properties or decorative choice. However, due to some basic hydrodynamic experiments performed by Hiroshi Kawase, there is some evidence to suggest that there may be more to building the nest than solely attracting a mate. Several questions therefore arise regarding the nest. Is there an evolutionary reason that male puffer fish build these nests? Which characteristics of a nest make it attractive to female puffer fish? Are the eggs safer in a nest, perhaps from incoming currents? How exactly does fluid flow through nest, and can it be replicated and simulated? This project begins to tackle these questions through a numerical investigation (CFD) of the fluid flow through the nest in order to identify key fluid dynamic features, which may play a significant role in egg incubation and spawning using Star CCM+

A foundation for reliable spatial proteomics data analysis.

Quantitative mass-spectrometry-based spatial proteomics involves elaborate, expensive, and time-consuming experimental procedures, and considerable effort is invested in the generation of such data. Multiple research groups have described a variety of approaches for establishing high-quality proteome-wide datasets. However, data analysis is as critical as data production for reliable and insightful biological interpretation, and no consistent and robust solutions have been offered to the community so far. Here, we introduce the requirements for rigorous spatial proteomics data analysis, as well as the statistical machine learning methodologies needed to address them, including supervised and semi-supervised machine learning, clustering, and novelty detection. We present freely available software solutions that implement innovative state-of-the-art analysis pipelines and illustrate the use of these tools through several case studies involving multiple organisms, experimental designs, mass spectrometry platforms, and quantitation techniques. We also propose sound analysis strategies for identifying dynamic changes in subcellular localization by comparing and contrasting data describing different biological conditions. We conclude by discussing future needs and developments in spatial proteomics data analysis..G., C.M.M., and M.F. were supported by the European Union 7th Framework Program (PRIME-XS Project, Grant No. 262067). L.M.B. was supported by a BBSRC Tools and Resources Development Fund (Award No. BB/K00137X/1). T.B. was supported by the Proteomics French Infrastructure (ProFI, ANR-10-INBS-08). A.C. was supported by BBSRC Grant No. BB/D526088/1. A.J.G. was supported by BBSRC Grant No. BB/E024777/ and a generous gift from King Abdullah University for Science and Technology, Saudi Arabia. D.J.N.H. was supported by a BBSRC CASE studentship (BB/I016147/1)

Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination, and repair) and are dynamic structures that adopt either open or closed conformations, the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core, an ideal structure to interact with open DNA junction cavities. Combining experimental studies and MD simulations, we show that an Au pillarplex can bind DNA 4-way (Holliday) junctions in their open form, a binding mode not accessed by synthetic agents before. Pillarplexes can bind 3-way junctions too, but their large size leads them to open up and expand that junction, disrupting the base pairing, which manifests in an increased hydrodynamic size and lower junction thermal stability. At high loading, they rearrange both 4-way and 3-way junctions into Y-shaped forks to increase the available junction-like binding sites. Isostructural Ag pillarplexes show similar DNA junction binding behavior but lower solution stability. This pillarplex binding contrasts with (but complements) that of metallo-supramolecular cylinders, which prefer 3-way junctions and can rearrange 4-way junctions into 3-way junction structures. The pillarplexes’ ability to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures. In human cells, the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher-order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction binders into organometallic chemistry

Clinical and health economic evaluation of a post-stroke arrhythmia monitoring service

Atrial fibrillation (AF) is a major cause of recurrent stroke and transient ischaemic attack (TIA) in the UK. As many patients can have asymptomatic paroxysmal AF, prolonged arrhythmia monitoring is advised in selected patients following a stroke or TIA. This service evaluation assessed the clinical and potential health economic impact of prolonged arrhythmia monitoring post-stroke using R-TEST monitoring devices.This was a prospective, case-controlled, service evaluation in a single health board in the North of Scotland. Patients were included if they had a recent stroke or TIA, were in sinus rhythm, and did not have another indication for, or contraindication to, oral anticoagulation. A health economic model was developed to estimate the clinical and economic value delivered by the R-TEST monitoring. Approval to use anonymised patient data in this service evaluation was obtained.During the evaluation period, 100 consecutive patients were included. The average age was 70 ± 11 years, 46% were female. Stroke was the presenting complaint in 83% of patients with the other 17% having had a TIA. AF was detected in seven of 83 (8.4%) patients who had had a stroke and one of 17 (5.9%) patients with a TIA. Health economic modelling predicted that adoption of R-TEST monitoring has a high probability of demonstrating both clinical and economic benefits.In conclusion, developing a post-stroke arrhythmia monitoring service using R-TEST devices is feasible, effective at detecting AF, and represents a probable clinical and economic benefi

Variability in IC5070: two young stars with deep recurring eclipses

Investigating the structure and properties of the innermost parts of protoplanetary accretion disks on sub-AU scales is currently only possible via indirect methods. One option to map the planet-forming zone is to search for occultations of the central young stellar object (YSO) by circumstellar material, e.g., warps or clumps in the inner disks. Such disk eclipses typically last hours to days (Cody et al. 2014) and have been identified in massive HAeBe stars such as UX Ori (Herbst & Shevchenko 1999) and lower mass objects such as AA Tau (Bouvier et al. 1999). Of particular interest are quasi-periodic dimming events. They allow distance determinations of the occulting material from the central star. In such cases the actual azimuthal physical extent of the material can be determined from the duration of the dimming event relative to the period. Observations over several periods enable investigations into temporal changes in the line of sight column density distribution, and multi-wavelength data allows us to probe the dust scattering properties. Our citizen science project HOYS-CAPS (Froebrich et al. 2018) aims to identify such periodic dimming events around YSOs. We used this data-set to search for periodic signatures in light-curves from YSOs in the Pelican nebula (IC 5070). For this field we have ~200 individual observations in the V, R, and I-band filters, distributed over ~800 days. Hence, the average cadence is 4 days, but the most frequent gap (30%) between subsequent observations is 2 days. Observations are usually taken as 8 × 2 minutes integrations in all filters to achieve a consistent S/N

Multilingual markers of depression in remotely collected speech samples: A preliminary analysis

Background: Speech contains neuromuscular, physiological and cognitive components, and so is a potential biomarker of mental disorders. Previous studies indicate that speaking rate and pausing are associated with major depressive disorder (MDD). However, results are inconclusive as many studies are small and underpowered and do not include clinical samples. These studies have also been unilingual and use speech collected in controlled settings. If speech markers are to help understand the onset and progress of MDD, we need to uncover markers that are robust to language and establish the strength of associations in real-world data. // Methods: We collected speech data in 585 participants with a history of MDD in the United Kingdom, Spain, and Netherlands as part of the RADAR-MDD study. Participants recorded their speech via smartphones every two weeks for 18 months. Linear mixed models were used to estimate the strength of specific markers of depression from a set of 28 speech features. // Results: Increased depressive symptoms were associated with speech rate, articulation rate and intensity of speech elicited from a scripted task. These features had consistently stronger effect sizes than pauses. // Limitations: Our findings are derived at the cohort level so may have limited impact on identifying intra-individual speech changes associated with changes in symptom severity. The analysis of features averaged over the entire recording may have underestimated the importance of some features. // Conclusions: Participants with more severe depressive symptoms spoke more slowly and quietly. Our findings are from a real-world, multilingual, clinical dataset so represent a step-change in the usefulness of speech as a digital phenotype of MDD

Organometallic Pillarplexes that bind DNA 4-way Holliday Junctions and Forks.

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination and repair) and are dynamic structures which adopt either open or closed conformations, with the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core giving them an ideal structure to interact with the central cavities of open DNA junctions. Combining experimental studies and MD simulations we show that an Au pillarplex can bind DNA 4-way junctions (Holliday junctions) in their open form, a binding mode not accessed by synthetic agents before. The Au pillarplexes can bind designed 3-way junctions too but their large size leads them to open up and expand that junction, disrupting the base pairing which manifests in an increase in hydrodynamic size and a lower junction thermal stability. At high loading they re-arrange both 4-way and 3-way junctions into Y-shaped DNA forks to increase the available junction-like binding sites. The structurally related Ag pillarplexes show similar DNA junction binding behaviour, but a lower solution stability. This pillarplex binding contrasts with (but complements) that of the metallo-supramolecular cylinders, which prefer 3-way junctions and we show can rearrange 4-way junctions into 3-way junction structures. The ability of pillarplexes to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures where they are key interconnecting components. Studies in human cells, confirm that the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction-binders into organometallic chemistry