Iterative Music

An interactive installation of Iterative Music (a process developed by Dr Steve Gisby) in which audience members were able to upload their own sounds over a local network

In order and out of time: Compositions exploring processes, polymeters and balance

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.These compositions explore concepts based on processes and polymeter. Drawing on influences ranging from Steve Reich to Conlon Nancarrow and Nik Bärtsch they use and develop an approach to rhythmic thinking based on ostinati constructed of layers of different speeds. Through the use of click tracks, they look at how an ensemble can be enabled to perform rhythms that, without the electronic support, would be unplayable – crossing a line between the possible and the impossible. By means of processes built on a number of different ideas, the pieces explore how these can be used to affect both the behaviour and evolution of musical material, as well as using them to create fixed structures within which I then move subjectively and more intuitively. The question of balance, of moving between two points or approaches that are seemingly opposites, has also been examined: looking at how the journey affects the destination, where the simple becomes complex, and where personal meets impersonal

Performing temporal processes

This article explores the way that the performance of temporal processes in recent contemporary music reveals something about the nature of musical time. Process music deals with time as a part of its material, offering the opportunity to experience time as time: the expression and experience of units of time that are defined by, and enclose, processes, in works whose forms are defined by their durations. The nature of time in four examples, by Alistair Zaldua, Mathias Spahlinger, Steve Gisby, and Sophie Stone, is discussed with reference to theories of time by Jonathan D. Kramer and Henri Bergson

Normmodellen som analysverktyg för offentlig förvaltning

Den här uppsatsen vill belysa Normmodellen som ett analysredskap för institutionell utveckling inom offentlig förvaltning. På vilket sätt behöver den offentliga förvaltningen organisera sig för att möta kraven från en globaliserad värld, som kommer att ställa krav på den offentliga förvaltningens demokratiska organisationsform. En hierarkisk styrd kommunal organisation kommer att få det svårt att möta inflytandet från omvärlden. Förändringarna sker snabbt och nya regler från EU eller andra system kommer att påverka utvecklingen. Kapitalet har genom alla tider rört sig fritt över gränserna och nu kommer regler och system, som ställer krav på den offentliga förvaltningen. Hur skapar man ett demokratiskt system som bygger på individernas valda företrädare och det som de står för, samtidigt som samma förvaltning skall möta krav som kommer från andra delar av världen. Hur blir vi som medborgare inkluderade i utvecklingen och hur blir våra offentliga organisationer delar av detta? Jag har i ett case där jag undersökt vuxenutbildningens utveckling och förutsättningar att utvecklas i en delregion. Där kommunal förvaltning möter andra kommunala förvaltningar och där man löst problemet genom att låta den större kommunen bestämma. Risken är att man fråntar de mindre kommunernas medborgare inflytande över sin vuxenutbildning. I caset har man löst det genom att inrätta en gemensam styrelse för vuxenutbildningen med företrädare från kommunerna, men den större kommunen har majoriteten i styrelsen. Styrelsen för i praktiken en undanskymd tillvaro i konkurrens med ett kommunförbund för Gymnasieskolan, som handhar en del av vuxenutbildningen. Styrelsen och dess verksamhet handhas av en operativ enhet. Denna operativa enhet är organisatoriskt underställd den större kommunen. Samverkan sker med en rad olika organisationer av offentlig och halv offentlig karaktär. Det är statliga bolag och ideella folkbildningsorganisationer, förutom de kommunala utbildningsaktörerna. Jag har i uppsatsen med stöd av olika teoretiska modeller och resonemang visat på de förutsättningar som krävs för att skapa en nätverksbaserad organisation där de medverkande aktörerna inkluderas och därmed kan påverka utvecklingen även i delregionen. De teoretiska modellerna har hämtat sin näring från Hydéns normmodell kombinerat med framför allt Habermas och Santos modeller för hur normer etableras och förändras. Mitt syfte har varit att visa hur normmodellen skulle kunna vara ett analysverktyg för att utveckla hållbara offentliga organisationer där metastyrning och "governance" är centrala. En offentlig förvaltning som effektivt och rationellt kan leverera det som brukarna efterfrågar. En offentlig förvaltning som kan hantera komplexiteten i en allt mer globaliserad värld. Det gäller för den offentliga förvaltningen att bygga samverkan som inkluderar aktörerna och stödjer förtroende och tillit mellan dessa. En organisation eller nätverk av aktörer skapar gemensamma normer som jag menar baserar sig på gemensamma referenspunkter. Jag har relaterat dessa referenspunkter till Scheins modell för grundläggande värderingar - styrande värdering - artefakt. Referenspunkten utgörs av en artefakt i form av ett grundläggande ord eller begrepp kring vilket aktörerna samlas. Med stöd av normmodellen som analysverktyg kommer man fram till individernas grundläggande värderingar. Normmodellen ger genom att man kombinerar frågor som rör förutsättningar för Systemet/ Strukturen, Kunskap och Vilja/Drivkraft en samlad bild av hur individerna i en organisation ser på vad som är gemensamt värdeskapande och också anger normen för deras handlande. I caset visade det sig att det som alla samlades kring, för att skapa en gemensam värdegrund var ordet neutral. Den samlande operativa enheten måste vara neutral för att skapa förtroende och tillit, menade de intervjuade. Den operativa enheten i caset ansågs vara neutral och fick därmed också förtroendet att samordna aktiviteterna. Styrningen av den operativa enheten och därmed den gemensamma nätverksorganisationen är inte renodlade i caset. Det finns en sammanblandning av ekonomi struktur och värderingar som innebär att den styrande värderingen Scheins modell inte stödjer innebörden i artefakten och begreppet neutral. Det innebär svårigheter att skapa ett nätverk av vuxenutbildnings-aktörer som är hållbart. Resultatet av analys med stöd av normmodellen är att den fungerar som ett instrument, för att synliggöra organisationers normer och värdering. Normmodellen behöver kombineras med andra modeller som Santos och Habermas, för att tydliggöra systemets struktur. Intervjuerna ger en bra bild av kunskap och vilja/drivkraft, som jag ser som de grundläggande värderingarna Scheins modell. De styrande värderingarna kan man få till viss del genom intervjuerna, men de behöver filtreras och analyseras utifrån olika aspekter som makt, medium enligt Habermas definition, berättelser om förhållanden, beslut i styrelser eller motsvarande. Denna information ser jag behöver processas inom ramen för systemet innan det blir en del av analysen i nommodellen

An exploration of career changers’ perceptions of the transformation process and how they recaptured career success

Research suggests that reasons for selecting, remaining in or changing career have undergone radical change over the last fifty years (Baruch, 2004). These patterns are said to be the result of changes in the ways individuals think about their career (Hall, 1996; DeFillippi & Arthur, 1994; Maineiro & Sullivan, 2005) which have led them to feel more at ease with boundary crossing (Arthur, 2014). To date, however, complex career change i.e. switching from one occupation to another (Parnes, 1954) has received relatively little attention (Jiang et al, 2019). There have been continued calls (e.g. Sullivan & Ariss, 2019) for more research in this area in order to understand the challenges associated with the transition process, particularly in relation to status loss i.e. becoming a novice having previously being an expert (Hoeksel et al, 2019). In addition, whilst career success literature is abundant (e.g. Heslin, 2005; Shultz et al, 2019) studies offering insights into ‘how’ it is achieved are sparse (Carless & Arnup, 2010). Calls for research in this area focus on the need to consider the role of learning (e.g. Hunter, 2019) especially during the so-called ‘honeymoon’ period and upto five years post-change (Zhou et al, 2017). This pattern continues in the learning literature too where, despite criticisms of formal learning (e.g. Boud, 1999; Wang et al, 2013), research looking at the use and value of informal learning continues to be scarce (e.g. Hoeksel et al, 2019). Furthermore, rather than looking at what learning needs complex career changers have (Anderson et al, 2014), ‘what works’ and why it is valued (e.g. Brown, 2015; Logan et al, 2016) or links between learning activities and longer-term outcomes (Tack et al, 2018; MacPhail et al, 2019), existing learning research is narrowly focused on ‘silos’ or specific types/methods of learning (Cerasoli et al, 2018). To address these gaps in current knowledge and to respond to calls for research which reflects the individual’s voice (Dries & Verbruggen, 2011; Arthur et al, 2005) this study adopted a qualitative approach. In addition, given the challenge of collecting tacit data, especially in relation to complex and/or emotional experiences such as career change, multiple methods were judged to be beneficial (King, 2004); in this case 18 complex career changers (teachers turned teacher-educators, healthcare practitioners turned academics, and practitioners turned teachers) took part in semi-structured interviews and completed Rich Pictures (Bell & Morse, 2013b) Thematic analysis of the data revealed themes across three main domains: ‘occupational re�orientation’, ‘recapturing success’, and ‘incremental learning’. Findings show that, whilst a risky and destabilising experience, for individuals in this study complex change was a restorative experience i.e. enabled them to get closer to what had become important to them. Recapturing career success, however, was subject to a complex interplay between transition stage (early or later), related psychological factors (e.g. risk, trust), and choice of learning method(s)

Seamless editing of the chloroplast genome in plants

BACKGROUND: Gene editing technologies enable the precise insertion of favourable mutations and performance enhancing trait genes into chromosomes whilst excluding all excess DNA from modified genomes. The technology gives rise to a new class of biotech crops which is likely to have widespread applications in agriculture. Despite progress in the nucleus, the seamless insertions of point mutations and non-selectable foreign genes into the organelle genomes of crops have not been described. The chloroplast genome is an attractive target to improve photosynthesis and crop performance. Current chloroplast genome engineering technologies for introducing point mutations into native chloroplast genes leave DNA scars, such as the target sites for recombination enzymes. Seamless editing methods to modify chloroplast genes need to address reversal of site-directed point mutations by template mediated repair with the vast excess of wild type chloroplast genomes that are present early in the transformation process. RESULTS: Using tobacco, we developed an efficient two-step method to edit a chloroplast gene by replacing the wild type sequence with a transient intermediate. This was resolved to the final edited gene by recombination between imperfect direct repeats. Six out of 11 transplastomic plants isolated contained the desired intermediate and at the second step this was resolved to the edited chloroplast gene in five of six plants tested. Maintenance of a single base deletion mutation in an imperfect direct repeat of the native chloroplast rbcL gene showed the limited influence of biased repair back to the wild type sequence. The deletion caused a frameshift, which replaced the five C-terminal amino acids of the Rubisco large subunit with 16 alternative residues resulting in a ~30-fold reduction in its accumulation. We monitored the process in vivo by engineering an overlapping gusA gene downstream of the edited rbcL gene. Translational coupling between the overlapping rbcL and gusA genes resulted in relatively high GUS accumulation (~0.5 % of leaf protein). CONCLUSIONS: Editing chloroplast genomes using transient imperfect direct repeats provides an efficient method for introducing point mutations into chloroplast genes. Moreover, we describe the first synthetic operon allowing expression of a downstream overlapping gene by translational coupling in chloroplasts. Overlapping genes provide a new mechanism for co-ordinating the translation of foreign proteins in chloroplasts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12870-016-0857-6) contains supplementary material, which is available to authorized users

Characterisation of ACBD3 and PI4Kβ expression in breast cancer and the effects of ACBD3 overexpression

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel UniversityTargeted breast cancer treatments are essential for increasing chemotherapy effectiveness whilst simultaneously reducing side effects and are the focus of a whole generation of drug development in cancer and elsewhere. The ACBD3 gene encodes an essential structural tether protein of the same name that has an unusually large number of cellular roles, diverse binding partners, and few redundancies. Chromosome 1q is frequently amplified in breast cancer and the ACBD3 locus (1q42.12) was previously found to be amplified in multiple breast cell lines and primary breast tumours. Previous research found that ACBD3 mRNA was upregulated in breast tumour tissue matched against adjacent normal tissue and that ACBD3 overexpression promoted cancer stem cell renewal and activated the Wnt/β-Catenin signalling pathway in breast cancer cell lines. Due to the broad functions of ACBD3 and its contextual role in cells it was hypothesised that ACBD3 expression may have other affects in breast cancer. ACBD3 was overexpressed at the mRNA and protein level in breast cancer patient tumours compared to normal tissue and mRNA expression over the median value was detrimental for breast cancer patient survival, relapse free survival and distant metastasis free survival. IHC staining of breast cancer and normal breast tissue cores found that ACBD3 was highly expressed in epithelial ductal cells. ACBD3 mRNA and protein expression was higher in a panel of breast cancer cell lines compared to a normal like breast cell line and ER+ cell lines had the highest protein expression of ACBD3. ACBD3 mRNA and protein expression was upregulated in a previously engineered T47D everolimus chemotherapy resistant cell, the T47D breast cancer cell line was transfected with eGFP-ACBD3 but this did not affect everolimus resistance. ACBD3 overexpression did increase cell growth and there were also a number of expression changes to oncoproteins. A GOLD domain deletion mutant of ACBD3 was constructed and this led to more oncoprotein expression changes when expressed in the T47D cell line. Transcriptional and translational regulation are sensitive to cell density which has implications for all ex vivo study of ACBD3 and several compounds have been found that augment ACBD3 expression. ACBD3 was hypothesised to be a marker of progression in breast cancer and may promote a Luminal B pathology over Luminal A. its overexpression increased growth in a Luminal A cell line, increased expression of proteins associated with inflammation and secretion and reduced immunogenic protein expression. Luminal B patients had the largest reduction in relapse free survival when ACBD3 mRNA expression was high. ACBD3 expression appears to be a biomarker for breast cancer patient outcomes and may have some validity in predicting response to therapy and was also associated with ER+ and signalling. New mechanisms by which ACBD3 might cause inflammation were determined in addition to known roles for ACBD3 in redox stress and in iron import. ACBD3 also reduced immunogenic proteins when overexpressed. ACBD3 is certainly associated with worse outcomes and with progression in breast cancer and ACBD3 dependent pathways should be considered as a target for treatment in the future. The consensus of these results agree that ACBD3 expression in breast cancer is associated with characteristics of stemness and that ACBD3 may decrease immune system detection in addition to Wnt signalling.Breast Cancer Hope and Brunel University Londo