Visualising ribosome profiling and using it for reading frame detection and exploration of eukaryotic translation initiation

Ribosome profiling (ribo-seq) is a recently developed technique that provides genomewide information on protein synthesis (GWIPS) in vivo. The high resolution of ribo-seq is one of the exciting properties of this technique. In Chapter 2, I present a computational method that utilises the sub-codon precision and triplet periodicity of ribosome profiling data to detect transitions in the translated reading frame. Application of this method to ribosome profiling data generated for human HeLa cells allowed us to detect several human genes where the same genomic segment is translated in more than one reading frame. Since the initial publication of the ribosome profiling technique in 2009, there has been a proliferation of studies that have used the technique to explore various questions with respect to translation. A review of the many uses and adaptations of the technique is provided in Chapter 1. Indeed, owing to the increasing popularity of the technique and the growing number of published ribosome profiling datasets, we have developed GWIPS-viz (http://gwips.ucc.ie), a ribo-seq dedicated genome browser. Details on the development of the browser and its usage are provided in Chapter 3. One of the surprising findings of ribosome profiling of initiating ribosomes carried out in 3 independent studies, was the widespread use of non-AUG codons as translation initiation start sites in mammals. Although initiation at non-AUG codons in mammals has been documented for some time, the extent of non-AUG initiation reported by these ribo-seq studies was unexpected. In Chapter 4, I present an approach for estimating the strength of initiating codons based on the leaky scanning model of translation initiation. Application of this approach to ribo-seq data illustrates that initiation at non-AUG codons is inefficient compared to initiation at AUG codons. In addition, our approach provides a probability of initiation score for each start site that allows its strength of initiation to be evaluated.

A programmer's environment for music analysis

A model for representing music scores in a form suitable for general processing by a music-analyst-programmer is proposed and implemented. Typical input to the model consists of one or more pieces of music which are encoded in a file-based score representation. File-based representations are in a form unsuited for general processing, as they do not provide a suitable level of abstraction for a programmer-analyst. Instead, a representation is created giving a programmer's view of the score. This frees the analyst-programmer from implementation details, that otherwise would form a substantial barrier to progress. The score representation uses an object-oriented approach to create a natural and robust software environment for the musicologist. The system is used to explore ways in which it could benefit musicologists. Methodologies for analysing music corpora are presented in a series of analytic examples which illustrate some of the potential of this model. Proving hypotheses or performing analysis on corpora involves the construction of algorithms. Some unique aspects of using this score model for corpus-based musicology are: - Algorithms impose a discipline which arises from the necessity for formalism. - Automatic analysis enables musicologists to complete tasks that otherwise would be infeasible because of limitations of their energy, attentiveness, accuracy and time.

Study abroad and complexity, accuracy and fluency (CAF) development: a longitudinal investigation of French and Chinese Learners of L2 English

This longitudinal study tracked third-level French (n=10) and Chinese (n=7) learners of English as a second language (L2) during an eight-month study abroad (SA) period at an Irish university. The investigation sought to determine whether there was a significant relationship between length of stay (LoS) abroad and gains in the learners' oral complexity, accuracy and fluency (CAF), what the relationship was between these three language constructs and whether the two learner groups would experience similar paths to development. Additionally, the study also investigated whether specific reported out-of-class contact with the L2 was implicated in oral CAF gains. Oral data were collected at three equidistant time points; at the beginning of SA (T1), midway through the SA sojourn (T2) and at the end (T3), allowing for a comparison of CAF gains arising during one semester abroad to those arising during a subsequent semester. Data were collected using Sociolinguistic Interviews (Labov, 1984) and adapted versions of the Language Contact Profile (Freed et al., 2004). Overall, the results point to LoS abroad as a highly influential variable in gains to be expected in oral CAF during SA. While one semester in the TL country was not enough to foster statistically significant improvement in any of the CAF measures employed, significant improvement was found during the second semester of SA. Significant differences were also revealed between the two learner groups. Finally, significant correlations, some positive, some negative, were found between gains in CAF and specific usage of the L2. All in all, the disaggregation of the group data clearly illustrates, in line with other recent enquiries (e.g. Wright and Cong, 2014) that each individual learner's path to CAF development was unique and highly individualised, thus providing strong evidence for the recent claim that SLA is "an individualized nonlinear endeavor" (Polat and Kim, 2014: 186).

Within the carnal: re-reading Merleau-Ponty through the language of drawing

In order to present visual art as a paradigm for philosophy, Merleau-Ponty investigated the creative processes of artists whose work corresponded closely with his philosophical ideas. His essays on art are widely valued for emphasising process over product, and for challenging the primacy of the written word in all spheres of human expression. While it is clear that he initially favoured painting, Merleau-Ponty began to develop a much deeper understanding of the complexities of how art is made in his late work in parallel with his advancement of a new ontology. Although his ontology remains unfinished and only exists as working notes and a manuscript entitled The Visible and Invisible, Merleau-Ponty had begun to appreciate the fundamental role drawing plays in the making of art and the creation of a language of expression that is as vital as the written or spoken word. Through an examination of Merleau-Ponty’s unfinished manuscript and working notes my thesis will investigate his working methods and use of materials and also explore how he processed his ideas by using my own art practice as the basis of my research. This research will take the form of an inquiry into how the unfinished and incomplete nature of text and artworks, while they are still ‘works in progress’, can often reveal the more human and carnal components of creative processes. Applying my experience as a practitioner and a teacher in an art school, I focus on the significance of drawing practice for Merleau-Ponty’s later work, in order to rebalance an overemphasis on painting in the literature. Understanding the differences between these two art forms, and how they are taught, can offer an alternative engagement with Merleau-Ponty’s later work and his struggle to find a language to express his developing new ontology. In addition, by re-reading his work through the language of drawing, I believe we gain new insights which reaffirm Merleau-Ponty's relevance to contemporary art making and aesthetics.