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.

The political philosophy of Miki Kiyoshi: A close reading of the philosophical foundations of cooperative communitarianism

The thesis is a historical and philological study of the mature political theory of Miki Kiyoshi (1897-1945) focused on Philosophical Foundations of Cooperative Communitarianism (1939), a full translation of which is included. As the name suggests, it was a methodological and normative communitarianism, which critically built on liberalism, Marxism and Confucianism to realise a regional political community. Some of Miki’s Western readers have wrongly considered him a fascist ideologue, while he has been considered a humanist Marxist in Japan. A closer reading cannot support either view. The thesis argues that the Anglophone study of Japanese philosophy is a degenerating research programme ripe for revolution in the sense of returning full circle to an original point. That means returning to the texts, reading them contextually and philologically, in principle as early modern European political theory is read by intellectual historians, such as the representatives of Cambridge School history of political thought. The resulting reading builds critically on the Japanese scholarship and relates it to contemporary Western and postcolonial political theory and the East Asian tradition, particularly neo-Confucianism. The thesis argues for a Cambridge School perspective radicalised by the critical addendum of geo-cultural context, supplemented by Geertzian intercultural hermeneutics and a Saidian ‘return to philology’. As against those who have seen radical reorientations in Miki’s political thought, the thesis finds gradual progression and continuity between his neo-Kantian, existentialist, Marxian anthropology, Hegelian and finally communitarian phases. The theoretical underpinnings are his philosophical anthropology, a structurationist social theory of praxis, and a critique of liberalism, Marxism, nationalism and idealism emphasising concrete as opposed to abstract theory and the need to build on existing cultural traditions to modernise rather than westernise East Asia. This post-Western fusion was imagined to be the beginning of a true and pluralistic universalism.

Nihilism and emptiness: Nishitani's encounter with Nietzsche

In this thesis, I examine the relationship between the Kyoto School philosopher, Nishitani Keiji, and the work of Friedrich Nietzsche, focusing on the two thinkers’ respective approaches to the problem of nihilism. The work begins by positioning Nishitani’s interpretation of Nietzsche’s account of nihilism with reference to diverse readings of Nietzsche in Western scholarship. I then consider the development of Nishitani’s reading of Nietzsche from his lecture series on nihilism, The Self- Overcoming of Nihilism, through to his magnum opus, Religion and Nothingness. I make two key contributions to recent scholarly debate on Nishitani’s relationship to Nietzsche. The first is to emphasise the importance of Nishitani’s response to the idea of eternal recurrence for understanding his critical approach to Nietzsche’s thinking. I argue against the view, offered by Bret Davis, that Nishitani’s criticisms of Nietzsche are primarily based on the former’s negative assessment of the idea of will to power. The second contribution is to situate Nishitani’s critical approach to eternal recurrence within his broader attempt to formulate a Zen-influenced conception of temporality and historicity. I then argue for the necessity of this conceptual background for coming to grips with his conception of the ‘transhistorical’ grounds of historicity in emptiness (śūnyatā), as outlined in the later chapters of Religion and Nothingness.

Reading Lydgate's Troy Book: patronage, politics, and history in Lancastrian England

This thesis, Reading Lydgate's Troy Book: Patronage, Politics and History in Lancastrian England, discusses the relationship between John Lydgate as a court poet to his patron Henry V. I contend that the Troy Book is explored as a vehicle to propagate the idea that the House of Lancaster is the legitimate successor to King Richard II in order to smooth over the usurpation of 1399. Paul Strohm's England's Empty Throne was a key influence to the approach of this thesis' topic. I examine that although Chaucer had a definitive impact on Lydgate's writing, Lydgate is able to manipulate this influence for his own ambitions. In order to enhance his own fame, Lydgate works to promote Chaucer's canon so that as Chaucer's successor, he will inherit more prestige. The Trojan war is seen in context with the Hundred Years War, and can be applied contextually to political events. Lydgate presents characters that are vulnerable to human failings, and their assorted, complicated relationships. Lydgate modernises the Troy Book to reflect and enhance his Lancastrian society, and the thesis gives a contextual view of Lydgate's writing of the Troy Book. Lydgate writes for a more varied target audience than his thirteenth-century source, Guido delle Colonne, and there is a deliberation on the female characters of the Troy Book which promulgates the theory that Lydgate takes a proactive and empathetic interest in women's roles in society. Furthermore Lydgate has never really been accepted as a humanist, and I look at Lydgate's work from a different angle; he is a self-germinating humanist. Lydgate revives antiquity to educate his fifteenth-century audience, and his ambition is to create a memorial for his patron in the vernacular, and enhance his own fame as a poet separate from Chaucer's shadow.

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.

THE EFFECT OF A PROGRAM OF PORTABLE ELECTRONIC PIANO KEYBOARD EXPERIENCE ON THE ACQUISITION OF SIGHT-SINGING SKILL IN THE NOVICE HIGH SCHOOL CHORUS

The problem was to determine whether a method of aural and visual vocal training that included a program of portable electronic piano keyboard experience would be more effective in teaching sight-singing skills to novice high school chorus students than a method that included only aural and visual vocal training. A sub-problem was to determine whether novice chorus students enjoyed playing electronic keyboards in chorus as a reinforcement experience in sight-singing training. Students were randomly assigned to two treatment groups, tested with the Musical Aptitude Profile, Tonal Imagery, part A, and then trained separately. The experimental group sang repetitions of melodic patterns and utilized techniques associated with the Kodály Method while simultaneously playing keyboard. The comparison group received a similar treatment without using keyboards. The students were pre- and post-tested in sight-singing using the Vocal Sight-Reading Inventory. Results of the Analysis of Covariance using MAP scores as the covariate revealed no significant difference (p<.05) between post-test scores of the two groups. Improvement was noted in 96% of students from pre-test to post-test regardless of grouping. The repeated measures ANOVA revealed a significant relationship (p<.006) between aptitude group and post-test score. High aptitude students in both groups were found to benefit more from the training than low aptitude students. High aptitude keyboard group students achieved an average gain score that was 8.67 points higher than the comparison group. Of the total experimental group, 92% enjoyed playing keyboards in chorus. It is recommended that future research be undertaken to study the use of keyboards with advanced high school choruses and with uncertain singers in the high school chorus. Research is also needed to develop graded, valid, and reliable sight-singing tests for use in high school chorus. Techniques of the Kodály Method should be further investigated for use in high school sight-singing training.

Bayes and empirical-Bayes multiplicity adjustment in the variable-selection problem

This paper studies the multiplicity-correction effect of standard Bayesian variable-selection priors in linear regression. Our first goal is to clarify when, and how, multiplicity correction happens automatically in Bayesian analysis, and to distinguish this correction from the Bayesian Ockham's-razor effect. Our second goal is to contrast empirical-Bayes and fully Bayesian approaches to variable selection through examples, theoretical results and simulations. Considerable differences between the two approaches are found. In particular, we prove a theorem that characterizes a surprising aymptotic discrepancy between fully Bayes and empirical Bayes. This discrepancy arises from a different source than the failure to account for hyperparameter uncertainty in the empirical-Bayes estimate. Indeed, even at the extreme, when the empirical-Bayes estimate converges asymptotically to the true variable-inclusion probability, the potential for a serious difference remains. © Institute of Mathematical Statistics, 2010.

Missing data in randomized clinical trials for weight loss: scope of the problem, state of the field, and performance of statistical methods.

BACKGROUND: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.

Trash: a local solution to a global problem

Gemstone Team GREEN JUSTICE

Production and recognition bias of stylistic sentences using a story reading task.

Four experiments examined participants' ability to produce surface characteristics of sentences using an on-line story reading task. Participants read a series of stories in which either all, or the majority of sentences were written in the same "style," or surface form. Twice per story, participants were asked to fill in a blank consistent with the story. For sentences that contained three stylistic regularities, participants imitated either all three characteristics (Experiment 2) or two of the three characteristics (Experiment 1), depending on the proportion of in-style sentences. Participants demonstrated a recognition bias for the read style in an unannounced recognition task. When participants read stories in which the two styles were the dative/double object alternation, participants demonstrated a syntactic priming effect in the cloze task, but no consistent recognition bias in a later recognition test (Experiments 3 and 4).

Atherosclerosis: Viewing the problem from a different perspective including possible treatment options

This paper proposes that atherosclerosis is initiated by a signaling event that deposits calcium hydroxyapatite (Ca-HAP). This event is preceded by a loss of mechanical structure in the arterial wall. After Ca-HAP has been deposited, it is unlikely that it will be reabsorbed because the solubility product constant (K sp) is very small, and the large stores of Ca +2 and PO 4-3 in the bones oppose any attempts to dissolve Ca-HAP by decreasing the common ions. The hydroxide ion (OH -) of Ca-HAP can be displaced in nature by fluoride (F -) and carbonate (CO 3-2) ions, and it is proposed that anions associated with cholesterol ester hydrolysis and, in very small quantities, the enolate of 7-ketocholesterol could also displace the OH -of Ca-HAP, forming an ionic bond. The free energy of hydration of Ca-HAP at 310 K is most likely negative, and the ionic radii of the anions associated with the hydrolysis of cholesterol ester are compatible with the substitution. Furthermore, examination of the pathology of atherosclerotic lesions by Raman and NMR spectroscopy and confocal microscopy supports deposition of Ca-HAP associated with cholesterol. Investigating the affinity of intermediates of cholesterol hydrolysis for Ca-HAP compared to lipoproteins such as HDL, LDL, and VLDL using isothermic titration calorimetry could add proof of this concept and may lead to the development of a new class of medications targeted at the deposition of cholesterol within Ca-HAP. Treatment of acute ischemic events as a consequence of atherosclerosis with denitrogenation and oxygenation is discussed. © the author(s), publisher and licensee Libertas Academica Ltd.

Superresolution: an ill-posed problem in Fourier optics

info:eu-repo/semantics/published

The Superresolution Problem in Doppler Difference Laser Anemometry

info:eu-repo/semantics/published

Description of a procedure to identify strategies: The case of the tiles problem

In this paper we present a procedure to describe strategies in problems which can be solved using inductive reasoning. This procedure is based on some aspects of the analysis of the specific subject matter, concretely on the elements, the representation systems and the transformations involved. We show an example of how we used this procedure for the tiles problem. Finally we present some results and conclusions.

Nested heuristic methods for the location-routeing problem

The concept of 'nested methods' is adopted to solve the location-routeing problem. Unlike the sequential and iterative approaches, in this method we treat the routeing element as a sub-problem within the larger problem of location. Efficient techniques that take into account the above concept and which use a neighbourhood structure inspired from computational geometry are presented. A simple version of tabu search is also embedded into our methods to improve the solutions further. Computational testing is carried out on five sets of problems of 400 customers with five levels of depot fixed costs, and the results obtained are encouraging.