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DIY Connections and Collaborations: Mid-West to North-East
Get PDFAlternative music cultures can be found in various Irish cities and towns outside of the capital Dublin. These scenes may retain their own local idiosyncrasies, but those subscribing to do-it-yourself (DIY) ideals in Ireland are clearly influenced by sounds and styles from further afield. As punk mutated into different forms from the 1980s onwards, political and musical cues came from the countries to the East and West of Ireland - hardcore (Fairchild, 1995) from the United States, and anarcho-punk (Dines, 2004) from Britain. The DIY aesthetics of the early punk movements have since translated to numerous music genres and practices since, including rap, indie, and dance (Bennett, 2018) . This article looks at contemporary DIY practices in Ireland, with a specific focus on two urban centres approximately 300 kilometres apart from each other – Dundalk, in the north-east of the country and Limerick, in the mid-west. Both have burgeoning independent music scenes, with young music-makers across disparate genres (alternative rock, hip-hop, electronica) subscribing to the ideals of do-it-yourself through the self-promotion, recording and distribution of music. This article examines contemporary perspectives from practitioners involved in these scenes. It explores networks - formal and informal - that are developing, with a specific focus on collectives in the two locales investigated for this study
Time scales of physical change in the lake environment
Get PDFThermal stratification underpins most of the biogeochemical and ecological processes in lakes. The maximum depth of the surface layer in a lake (“epilimnion depth” or “mixed layer depth”), in particular, affects the vertical distribution of energy, organisms and organic materials in lakes. A full understanding of the epilimnion depth is essential for lake studies, especially given the potential sensitivity of this parameter to global climate change. There is, however, a lack of consistency in the definition of this metric in existing literature. There is also an absence of studies exploiting high-frequency data to examine the variability in epilimnion depth over time and across lakes. To address these gaps, a comprehensive comparison of methods was undertaken to estimate epilimnion depth using data from two European lakes. This showed that estimated epilimnion depth estimates varied substantially depending on the method and threshold used. There was also a high level of sensitivity to the critical threshold value used in calculations. A method defined as the shallowest depth where the density was 0.1 kg m-3 more than the surface density gave the most consistent results. Using the recommendations from the previous chapter, multi-lake comparison of mixed layer depth dynamics was conducted for 19 lakes, using data from a total of 100 summers. This study revealed large differences in the day-to-day variability of the summer epilimnion depth and emphasised the role of lake area in determining variability in this metric. Given that the epilimnion depth is a widespread and ecologically meaningful metric in limnology, these findings have far-reaching applications especially when predicting the impacts of extreme in-lake changes. A systematic literature review found that most studies that addressed the effects of climate extremes on in-lake changes based their metric of extremeness on local weather data. A comparison of weather-related extreme events and in-lake mixing events was undertaken for two sites over 30 years and found that that extreme weather-related and in-lake mixing events often did not co-occur. These results highlighted the importance of using in-lake based extreme event metrics for lake-focused science. Collectively, the research presented in this dissertation contributes towards rethinking existing and future methods in lake science for the protection of lake ecosystems
Return to Fingal: The heritage and practice of Irish traditional music in North County Dublin
Get PDFThis dissertation presents a critical examination of the heritage and practice of Irish traditional music today in North County Dublin, a local government administrative county also known as Fingal. The area has experienced much population growth and demographic change in recent years. This research critically examines the practice of the music within local community settings with a focus on recreational musicians and how they engage with the music, including learning and performing. An ecosystem approach is adopted in the examination, involving the application of a five-domain analytical framework developed by Schippers and Grant (2016), to comprehend an array of actors, physical and social factors, wider community and commercial influences and, not least, official actions at national and local levels that impact now on the practice of Irish traditional music in Fingal.
The research identifies an increase in interest in playing Irish traditional music in Fingal between circa 1980 and 2010. The increase was associated with particular locations within the county, while in many other areas the music continued to have limited visibility and that remains the position today. Engagement with the music has also weakened in some areas over the past decade. To understand why that should be so despite public investment and plans supporting traditional music being in place, the research examines national and local policies and actions to foster the music at county level. The methodology included undertaking interviews with 52 individuals drawn from across the community demographic. The dissertation presents detailed accounts of how ten individuals personally engage with traditional music and recognises a need for the development of a new vision and official measures to encourage and support recreational musicians engaging in participatory performance in their communities
Come Enjoy the Craic: Locating an Irish Traditional Music Festival in Drogheda
Get PDFThe Irish traditional music festival ‘Fleadh Cheoil na hÉireann’ was first held in Drogheda, Co. Louth in August 2018 and subsequently in August 2019. The host town benefitted not only economically during the festival, but also from enhanced investment in infrastructure and marketing. This created a legacy that has outlasted the event itself. Irish traditional music has typically been associated with the west of Ireland and narratives and marketing related to the tradition typically involves reference to rurality. As an urban place on the east coast near the border with Northern Ireland, Drogheda presented a new location and new spaces for the festivalisation of Irish traditional music culture while simultaneously requiring organisers to consider the use of urban public space for festival activities. The local authority was a significant stakeholder in Fleadh Cheoil na hÉireann in Drogheda and utilised the opportunity to create and disseminate an identity for the town and region that would have a legacy for tourism beyond the staging of the event. Using reflective ethnography and interviews with local authority representatives and the festival organisers, this study critically considers how towns are thinking about their public spaces in terms of outdoor staging, public congregation and access. This chapter focuses on the use of such public space during the festival and the development of an identity for Drogheda as a place of festivals. The chapter highlights the importance of urban 'public spaces' and their utilisation as something both local government policymakers and festival audiences are looking for. Such 'public spaces' once re-imagined are now seen as 'experience spaces' in which the quantity and variety of festival experience possibilities are vital
A Journey Towards a Community of Musical Practice Through Music Generation Louth's Introducing Strings Programme for Schools
Get PDFIntroducing Strings is a large-scale performance music education programme established by Music Generation Louth in 2012 to widen access to musical participation and learning amongst children and young people in Louth. This study provides context for and presents a critical reflection of the development of the programme. It highlights key successes of the programme over its initial nine years and identifies a number of challenges that have emerged during that period. It determines the critical success factors that enable the programme to make a deeper impact beyond its function of being an economically effective model of performance music education.
The research presented herein follows the model of a work-based project and, as a researcher, I provide both an emic perspective and an applied ethnomusicology approach. Throughout the project, this research informed and influenced the planning and programming choices for the MGL Introducing Strings programme, other whole class ensemble projects across Music Generation Louth. The learning has been disseminated across the Music Generation programme nationally and will continue to do so into the future. Themes that have emerged include musical enculturation and the development of communities of musical practice, partnership, performance, pathways for progression, pedagogy to include informal music teaching and learning, musical choices and continuing professional development for musician educators. This dissertation assesses the impact of one music performance education programme and its evolution towards achieving a community of musical practice in County Louth
Investigation of ion channels involved in cholinergic activity in mouse bronchial smooth muscles
Get PDFIn airway smooth muscle cells (ASMCs), multiple ion channels are expressed, however their involvement in cholinergic contractions have been controversial. In the present study, using isometric tension and live cell-Ca2+ imaging, the role of ion channels for instance TMEM16A, and voltage-dependent and independent Ca2+ channels were investigated in murine bronchial smooth muscle. CaCCinh- A01, benzbromarone and MONNA, three TMEM16A inhibitors inhibited sustained contractions rather than initial, suggesting involvement of TMEM16A on sustained part of cholinergic contractions. However, another TMEM16A inhibitor, Ani9 had little effect on cholinergic contractions. With the hypothesis that the other three inhibitors might be blocking L-type Ca2+ channels, their effects were tested after addition of nifedipine. Nifedipine (1 μM) itself reduced the effect of all of the concentrations of carbachol (CCh). However, TMEM16A inhibitors further reduced the responses when added in the presence of nifedipine. All three blockers increased intracellular Ca2+ concentration in calcium imaging experiments. With further investigation using 0 Ca2+ Hanks and caffeine, it was confirmed these blockers were causing Ca2+ release. Tetracaine (100 μM), ryanodine receptor blocker had an inhibitory effect on intracellular calcium increased by benzbromarone. Thus, confirming that TMEM16A blockers are causing Ca2+ release through ryanodine receptors.
Store operated calcium entry (SOCE) is a major pathway in Ca2+ signalling which is activated upon depletion of Ca2+ from the SR during excitation-contraction coupling. Apart from store refilling channels and L-type Ca2+ channels, a role in cholinergic activity for Ca2+ release channels on the SR has also been reported. Ca2+ release from SR in the smooth muscle occurs through IP3Rs and RyRs (Kotlikoff & Wang, 1998). This project also investigated the involvement of calcium released activated calcium channel (CRAC; voltage independent Ca2+ channel) on cholinergic activity after inhibiting L-type Ca2+ channel (voltage
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dependent Ca2+ channel). It was observed that blocking both the channels at the same time, completely inhibited CCh contractions of all concentrations. As similar effect was observed in Ca2+ signals induced by 0.3 μM CCh. It was also observed that after blocking CRAC channel using GSK-7975A, Ani9 has more of an inhibitory effect on cholinergic contractions. We have also found that in high KCl contractile activity in ASM, along with VDCC, Ca2+ release through RyR and CRAC channel are also actively involved.
The key findings of the project was that TMEM16A has minor role in cholinergic activator induced contractile activity in healthy murine bronchial smooth muscle. SOCE and Ca2+ release through RyR are majorly involved in maintaining contractile activity in ASM
Multi-model projections of future evaporation in a subtropical lake
Get PDFLake evaporation plays an important role in the water budget of lakes. Predicting lake evaporation responses to climate change is thus of paramount importance for the planning of mitigation and adaption strategies. However, most studies that have simulated climate change impacts on lake evaporation have typically utilised a single mechanistic model. Whilst such studies have merit, projected changes in lake evaporation from any single lake model can be considered uncertain. To better understand evaporation responses to climate change, a multi-model approach (i.e., where a range of projections are considered), is desirable. In this study, we present such multi-model analysis, where five lake models forced by four different climate model projections are used to simulate historic and future change (1901–2099) in lake evaporation. Our investigation, which focuses on sub-tropical Lake Kinneret (Israel), suggested considerable differences in simulated evaporation rates among the models, with the annual average evaporation rates varying between 1232 mm year−1 and 2608 mm year−1 during the historic period (1901–2005). We explored these differences by comparing the models with reference evaporation rates estimated using in-situ data (2000–2005) and a bulk aerodynamic algorithm. We found that the model ensemble generally captured the intra-annual variability in reference evaporation rates, and compared well at seasonal timescales (RMSEc = 0.19, R = 0.92). Using the model ensemble, we then projected future change in evaporation rates under three different Representative Concentration Pathway (RCP) scenarios: RCP 2.6, 6.0 and 8.5. Our projections indicated that, by the end of the 21st century (2070–2099), annual average evaporation rates would increase in Lake Kinneret by 9–22 % under RCPs 2.6–8.5. When compared with projected regional declines in precipitation, our projections suggested that the water balance of Lake Kinneret could experience a deficit of 14–40 % this century. We anticipate this substantial projected deficit combined with a considerable growth in population expected for this region could have considerable negative impacts on water availability and would consequently increase regional water stress
Mechanism of action of GoSlo-SR-5-6 on Kv7.4 channels
Get PDFMechanism of action of GoSlo-SR-5-6 on Kv7.4 channels
Voltage-gated K+ channels (Kv7) play important roles in a range of physiological functions such as sensory transduction, smooth muscle contraction, epithelial secretion and neuronal excitability (Soldovieri et al., 2011). In the airway smooth muscle cells (ASMC), Kv7.4 and Kv7.5 are predominantly expressed and play an important role in the regulation of airway diameter and activators of Kv7 channels have been shown to induce relaxation of ASMC (Brueggemann et al., 2018). In the lab previously, a family of compounds called the GoSlo-SR were developed (Roy et al., 2012; Roy et al., 2014). Among these, GoSlo-SR-5-6 (SR-5-6), was established as a potent and efficacious activator of Kv7.1, Kv7.4 and Kv7.5 channels and was less effective on Kv7.2 and Kv7.3. In Kv7.4 channels, SR-5-6 increased the G/Gmax to ~1.6 and shifted the V1/2 by ~-50 mV (Zavaritskaya et al., 2020).
Phosphatidylinositol-(4,5)-bisphosphate (PIP2) is a small membrane lipid known to be critical for Kv7 channel function (Gamper & Shapiro, 2007). PIP2 is known to increase Gmax, slow deactivation and negatively shift the V1/2 and therefore has very similar effects to SR-5-6 on Kv7.4 channels. Given that PIP2 could mimic the effects of SR-5-6, potential PIP2 binding residues were mutated and the effect of each mutant was examined in the absence and presence of SR-5-6. Consequently, in this thesis, the data presented is aimed at:
1) Identifying potential residues in Kv7.4, important for the effect of SR-5-6 and assessing the state-dependent effect of SR-5-6 on Kv7.4 channels.
2) Assessing the effect of SR-5-6 on drug-sensitive Kv7.4 channels domain swapped with drug insensitive Kv7.3.
3) Examining the role of PIP2 modulation and PIP2 binding residues on SR- 5-6 mediated activation of Kv7.4 channels.
The first results chapter investigated the role of drug binding residues of known activators, to look for potential binding sites for SR-5-6 in Kv7.4 channels. Although the effect of SR-5-6 was not abolished in any of the mutants studied in this chapter, a mutant (L249A) was found, which practically abolished the negative shift in activation V1/2 of Kv7.4 channels. Although this mutant abolished
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the effect of SR-5-6 on DV1/2, it failed to reduce its effect on G/Gmax. In the later part of this chapter, the state-dependent activity of SR-5-6 on Kv7.4 channels was investigated. The findings suggested that the effects of this drug appeared to be greater than WT Kv7.4 when the VSDs were locked in the resting state (E136R). Also, with the partially activated state mutant (E136R/R207E), the channels were open at exceptionally negative potentials, but SR-5-6 could still enhance G/Gmax. Overall, the results suggested that the effects of SR-5-6 were not state- dependent.
In the subsequent chapter, a chimeric approach was utilized between Kv7.3 and Kv7.4 channels and examined the effects of swapping each main domain of the Kv7.3 channel onto a Kv7.4 background. The rationale was based on the earlier demonstration by Dudem (2019) that Kv7.3 channels were substantially less sensitive to 10 μM SR-5-6 (DV1/2 ~-16 mV; G/Gmax ~1) than Kv7.4 channels. However, when the S3-S4 linker, S4 domain, the S4-S5 linker, S5 domain, S6 domain, C-terminus, voltage-sensing domain (S1-S4), pore domain (S5-PL-S6) were swapped and mutated non-conserved residues between Kv7.3 and Kv7.4, none of these swap constructs or mutant channels mitigated the effects of SR-5- 6. These data indicated that this approach was not effective at identifying a binding site for SR-5-6 in this channel.
The final results chapter examined whether interfering with PIP2 altered the effects of SR-5-6. When PIP2 was depleted using the voltage-sensitive phosphatase CiVSP, a clear reduction was observed in the effectiveness of SR- 5-6 to shift DV1/2 and the change in G/Gmax was significantly reduced. Similarly, when wortmannin was used to inhibit the replenishment of membrane PIP2, it abolished the effect of SR-5-6 on G/Gmax. These results demonstrated that PIP2 may play an important role in mediating the effects of SR-5-6, particularly on G/Gmax. Given the results of the above experiments, it was therefore surprising that the effects of SR-5-6 were not blocked when a number of PIP2 binding mutant channels were studied. Furthermore, a number of these mutations in Kv7.4 channels did not result in loss-of-current mutations as reported in other Kv7 channels, which was surprising. This suggested that Kv7.4 may either have different PIP2 binding residues or alternatively, more than one mutation was needed to reduce the binding PIP2 in Kv7.4 channels
Challenges Associated with the Adoption of Artificial Intelligence in Medical Device Software
Get PDFThe utilization of Artificial Intelligence (AI) has changed and enhanced several industries across the world, such as education, research, manufacturing and healthcare. The potential of AI to create new and enhanced applications that can benefit patients and physicians has created interest and enthusiasm, especially in a Medical Device Software (MDS) context. Although, the adoption of AI in MDS has also brought concerns for regulatory agencies and policymakers. The complexity of AI has challenged the standard requirements set by regulatory agencies, especially in the context of the differences between traditional MDS and AI. Additionally, the unique capacity of AI to continuous learning for optimal performance in real-world settings may also bring potential harm and risk to patients and physicians. The challenges discussed in this paper are in relation to: (1) Software Development Life Cycle (SDLC) frameworks; (2) learning processes and adaptability of AI algorithms; (3) explainability and traceability; and (4) conflictive terminology. At the end of this paper, conclusions and future work are presented to contribute to the safety and methodical implementation of AI in health care settings
