Hierarchical Multi-classification with Predictive Clustering Trees in Functional Genomics

Struyf, J., Dzeroski, S. Blockeel, H. and Clare, A. (2005) Hierarchical Multi-classification with Predictive Clustering Trees in Functional Genomics. In proceedings of the EPIA 2005 CMB Workshop

The Cambrian Muse: Welsh Identity and Hanoverian Loyalty in the Poems of Jane Brereton (1685-1740)

Prescott, S. (2005). The Cambrian Muse: Welsh Identity and Hanoverian Loyalty in the Poems of Jane Brereton (1685-1740). Eighteenth -Century Studies. 38(4), pp.587-603. RAE2008

A importância da marca no processo de tomada de decisão de compra industrial

Dissertação de Mestrado apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências da Comunicação, com especialização em Marketing e Comunicação Estratégica.

Contributo para o desenvolvimento de um Instrumento de Investigação Neuropsicológica

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Ciências Sociais, especialidade em Psicologia

Contributo para o desenvolvimento de um Instrumento de Investigação Neuropsicológica

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Ciências Sociais, especialidade em Psicologia

The Sensor Network Workbench: Towards Functional Specification, Verification and Deployment of Constrained Distributed Systems

As the commoditization of sensing, actuation and communication hardware increases, so does the potential for dynamically tasked sense and respond networked systems (i.e., Sensor Networks or SNs) to replace existing disjoint and inflexible special-purpose deployments (closed-circuit security video, anti-theft sensors, etc.). While various solutions have emerged to many individual SN-centric challenges (e.g., power management, communication protocols, role assignment), perhaps the largest remaining obstacle to widespread SN deployment is that those who wish to deploy, utilize, and maintain a programmable Sensor Network lack the programming and systems expertise to do so. The contributions of this thesis centers on the design, development and deployment of the SN Workbench (snBench). snBench embodies an accessible, modular programming platform coupled with a flexible and extensible run-time system that, together, support the entire life-cycle of distributed sensory services. As it is impossible to find a one-size-fits-all programming interface, this work advocates the use of tiered layers of abstraction that enable a variety of high-level, domain specific languages to be compiled to a common (thin-waist) tasking language; this common tasking language is statically verified and can be subsequently re-translated, if needed, for execution on a wide variety of hardware platforms. snBench provides: (1) a common sensory tasking language (Instruction Set Architecture) powerful enough to express complex SN services, yet simple enough to be executed by highly constrained resources with soft, real-time constraints, (2) a prototype high-level language (and corresponding compiler) to illustrate the utility of the common tasking language and the tiered programming approach in this domain, (3) an execution environment and a run-time support infrastructure that abstract a collection of heterogeneous resources into a single virtual Sensor Network, tasked via this common tasking language, and (4) novel formal methods (i.e., static analysis techniques) that verify safety properties and infer implicit resource constraints to facilitate resource allocation for new services. This thesis presents these components in detail, as well as two specific case-studies: the use of snBench to integrate physical and wireless network security, and the use of snBench as the foundation for semester-long student projects in a graduate-level Software Engineering course.

Functional genomics of motile commensal intestinal bacteria

Flagella confer upon bacteria the ability to move and are therefore organelles of significant bacteriological importance. The innate immune system has evolved to recognise flagellin, (the major protein component of the bacterial flagellar filament). Flagellate microbes can potentially stimulate the immune systems of mammals, and thus have significant immunomodulatory potential. The flagellum-biogenesis genotype and phenotype of Lactobacillus ruminis, an autochthonous intestinal commensal, was studied. The flagellum-biogenesis genotypes of motile enteric Eubacterium and Roseburia species were also investigated. Flagellin proteins were recovered from these commensal species, their amino-termini were sequenced and the proteins were found to be pro-inflammatory, as assessed by measurement of interleukin-8 (IL-8) secretion from human intestinal epithelial cell lines. For L. ruminis, this IL-8 secretion required signalling through Toll Like Receptor 5. A model for the regulation of flagellum-biogenesis in L. ruminis was inferred from transcriptomics data and bioinformatics analyses. Motility gene expression in this species may be under the control of a novel regulator, LRC_15730. Potential promoters for genes encoding flagellin proteins in the Eubacterium and Roseburia genomes analysed were inferred in silico. Relative abundances of the target Eubacterium and Roseburia species in the intestinal microbiota of 25 elderly individuals were determined. These species were found to be variably abundant in these individuals. Motility genes from these species were variably detected in the shotgun metagenome databases generated by the ELDERMET project. This suggested that a greater depth of sequencing, or improved evenness of sequencing, would be required to capture the full diversity of microbial functions for specific target or low abundance species in microbial communities by metagenomics. In summary, this thesis used a functional genomics approach to describe flagellum-mediated motility in selected Gram-positive commensal bacteria. The regulation of flagellum biosynthesis in these species, and the consequences of flagella expression from a host-interaction perspective were also considered.

Form-focused instruction in Irish-medium immersion education: a critical examination of teachers' perspectives and practices. A small-scale qualitative case study

It has been suggested that the less than optimal levels of students’ immersion language “persist in part because immersion teachers lack systematic approaches for integrating language into their content instruction” (Tedick, Christian and Fortune, 2011, p.7). I argue that our current lack of knowledge regarding what immersion teachers think, know and believe and what immersion teachers’ actual ‘lived’ experiences are in relation to form-focused instruction (FFI) prevents us from fully understanding the key issues at the core of experiential immersion pedagogy and form-focused integration. FFI refers to “any planned or incidental instructional activity that is intended to induce language learners to pay attention to linguistic form” (Ellis, 2001b, p.1). The central aim of this research study is to critically examine the perspectives and practices of Irish-medium immersion (IMI) teachers in relation to FFI. The study ‘taps’ into the lived experiences of three IMI teachers in three different IMI school contexts and explores FFI from a classroom-based, teacher-informed perspective. Philosophical underpinnings of the interpretive paradigm and critical hermeneutical principles inform and guide the study. A multi-case study approach was adopted and data was gathered through classroom observation, video-stimulated recall and semistructured interviews. Findings revealed that the journey of ‘becoming’ an IMI teacher is shaped by a vast array of intricate variables. IMI teacher identity, implicit theories, stated beliefs, educational biographies and experiences, IMI school cultures and contexts as well as teacher knowledge and competence impacted on IMI teachers’ FFI perspectives and practices. An IMI content teacher identity reflected the teachers’ priorities as shaped by pedagogical challenges and their educational backgrounds. While research participants had clearly defined instructional beliefs and goals, their roadmap of how to actually accomplish these goals was far from clear. IMI teachers described the multitude of choices and pedagogical dilemmas they faced in integrating FFI into experiential pedagogy. Significant gaps in IMI teachers’ declarative knowledge about and competence in the immersion language were also reported. This research study increases our understanding of the complexity of the processes underlying and shaping FFI pedagogy in IMI education. Innovative FFI opportunities for professional development across the continuum of teacher education are outlined, a comprehensive evaluation of IMI is called for and areas for further research are delineated.

Functional metagenomic analysis of the human gut microbiome to identify novel salt tolerance genes

The ability to adapt to and respond to increases in external osmolarity is an important characteristic that enables bacteria to survive and proliferate in different environmental niches. When challenged with increased osmolarity, due to sodium chloride (NaCl) for example, bacteria elicit a phased response; firstly via uptake of potassium (K+), which is known as the primary response. This primary response is followed by the secondary response which is characterised by the synthesis or uptake of compatible solutes (osmoprotectants). The overall osmotic stress response is much broader however, involving many diverse cellular systems and processes. These ancillary mechanisms are arguably more interesting and give a more complete view of the osmotic stress response. The aim of this thesis was to identify novel genetic loci from the human gut microbiota that confer increased tolerance to osmotic stress using a functional metagenomic approach. Functional metagenomics is a powerful tool that enables the identification of novel genes from as yet uncultured bacteria from diverse environments through cloning, heterologous expression and phenotypic identification of a desired trait. Functional metagenomics does not rely on any previous sequence information to known genes and can therefore enable the discovery of completely novel genes and assign functions to new or known genes. Using a functional metagenomic approach, we have assigned a novel function to previously annotated genes; murB, mazG and galE, as well as a putative brp/blh family beta-carotene 15,15’-monooxygenase. Finally, we report the identification of a completely novel salt tolerance determinant with no current known homologues in the databases. Overall the genes identified originate from diverse taxonomic and phylogenetic groups commonly found in the human gastrointestinal (GI) tract, such as Collinsella and Eggerthella, Akkermansia and Bacteroides from the phyla Actinobacteria, Verrucomicrobia and Bacteroidetes, respectively. In addition, a number of the genes appear to have been acquired via lateral gene transfer and/or encoded on a prophage. To our knowledge, this thesis represents the first investigation to identify novel genes from the human gut microbiota involved in the bacterial osmotic stress response.

A qualitative study of trends in patient preferences for the management of partial dentition

Objective: To identify factors influencing attitudes of partially dentate adults towards dental treatment in Ireland. Background: People are retaining more teeth later in life than ever before. Management of partially dentate older adults will be a major requirement for the future and it is important to determine factors which may influence patients’ attitudes to care. Methods: Subjects: A purposive sample of 22 partially dentate patients was recruited; 12 women and 12 men, ranging in age from 45 to 75 years. Data Collection: Semi-structured individual interviews. Results: Dental patients have increasing expectations in relation to (i) a more sophisticated approach to the management of missing teeth and (ii) their right to actively participate in decision making regarding the management of their tooth loss. There is some evidence of a cohort effect with younger patients (45–64 years) having higher expectations. Conclusions: The evidence of a cohort effect within this study in relation to higher patient expectations indicates that both contemporary and future patients are likely to seek a service based on conservation and restoration of missing teeth by fixed prostheses.

State building as strategy: An interrogation of NATO's comprehensive approach in Afghanistan between 2006 and 2011

The core of this thesis is the study of NATO’s Comprehensive Approach strategy to state building in Afghanistan between 2006 and 2011. It argues that this strategy sustained operational and tactical practices which were ineffective in responding to the evolved nature of the security problem. The thesis interrogates the Comprehensive Approach along ontological, empirical and epistemological lines and concludes that the failure of the Comprehensive Approach in the specific Afghan case is, in fact, indicative of underlying theoretical and pragmatic flaws which, therefore, generalize the dilemma. The research is pragmatic in nature, employing mixed methods (quantitative and qualitative) concurrently. Qualitative methods include research into primary and secondary literature sources supplemented with the author’s personal experiences in Afghanistan in 2008 and various NATO HQ and Canadian settings. Quantitative research includes an empirical case study focussing on NATO’s Afghan experience and its attempt at state building between 2006 and 2011. This study incorporates a historical review of NATO’s evolutionary involvement in Afghanistan incorporating the subject timeframe; offers an analysis of human development and governance related data mapped to expected outcomes of the Afghan National Development Strategy and NATO’s comprehensive campaign design; and interrogates the Comprehensive Approach strategy by means of an analysis of conceptual, institutional and capability gaps in the context of an integrated investigational framework. The results of the case study leads to an investigation of a series of research questions related to the potential impact of the failure of the Comprehensive Approach for NATO in Afghanistan and the limits of state building as a means of attaining security for the Alliance.

Accurate localized resolution of identity approach for linear-scaling hybrid density functionals and for many-body perturbation theory

© 2015 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.A key component in calculations of exchange and correlation energies is the Coulomb operator, which requires the evaluation of two-electron integrals. For localized basis sets, these four-center integrals are most efficiently evaluated with the resolution of identity (RI) technique, which expands basis-function products in an auxiliary basis. In this work we show the practical applicability of a localized RI-variant ('RI-LVL'), which expands products of basis functions only in the subset of those auxiliary basis functions which are located at the same atoms as the basis functions. We demonstrate the accuracy of RI-LVL for Hartree-Fock calculations, for the PBE0 hybrid density functional, as well as for RPA and MP2 perturbation theory. Molecular test sets used include the S22 set of weakly interacting molecules, the G3 test set, as well as the G2-1 and BH76 test sets, and heavy elements including titanium dioxide, copper and gold clusters. Our RI-LVL implementation paves the way for linear-scaling RI-based hybrid functional calculations for large systems and for all-electron many-body perturbation theory with significantly reduced computational and memory cost.

Evaluating functional network inference using simulations of complex biological systems.

MOTIVATION: Although many network inference algorithms have been presented in the bioinformatics literature, no suitable approach has been formulated for evaluating their effectiveness at recovering models of complex biological systems from limited data. To overcome this limitation, we propose an approach to evaluate network inference algorithms according to their ability to recover a complex functional network from biologically reasonable simulated data. RESULTS: We designed a simulator to generate data representing a complex biological system at multiple levels of organization: behaviour, neural anatomy, brain electrophysiology, and gene expression of songbirds. About 90% of the simulated variables are unregulated by other variables in the system and are included simply as distracters. We sampled the simulated data at intervals as one would sample from a biological system in practice, and then used the sampled data to evaluate the effectiveness of an algorithm we developed for functional network inference. We found that our algorithm is highly effective at recovering the functional network structure of the simulated system-including the irrelevance of unregulated variables-from sampled data alone. To assess the reproducibility of these results, we tested our inference algorithm on 50 separately simulated sets of data and it consistently recovered almost perfectly the complex functional network structure underlying the simulated data. To our knowledge, this is the first approach for evaluating the effectiveness of functional network inference algorithms at recovering models from limited data. Our simulation approach also enables researchers a priori to design experiments and data-collection protocols that are amenable to functional network inference.

Sea Urchin Body Plan Development and Evolution: An Integrative Transcriptomic Approach

My dissertation work integrates comparative transcriptomics and functional analyses to investigate gene expression changes underlying two significant aspects of sea urchin evolution and development: the dramatic developmental changes associated with an ecologically significant shift in life history strategy and the development of the unusual radial body plan of adult sea urchins.

In Chapter 2, I investigate evolutionary changes in gene expression underlying the switch from feeding (planktotrophic) to nonfeeding (lecithotrophic) development in sea urchins. In order to identify these changes, I used Illumina RNA-seq to measure expression dynamics across 7 developmental stages in three sea urchin species: the lecithotroph Heliocidaris erythrogramma, the closely related planktotroph Heliocidaris tuberculata, and an outgroup planktotroph Lytechinus variegatus. My analyses draw on a well-characterized developmental gene regulatory network (GRN) in sea urchins to understand how the ancestral planktotrophic developmental program was altered during the evolution of lecithotrophic development. My results suggest that changes in gene expression profiles occurred more frequently across the transcriptome during the evolution of lecithotrophy than during the persistence of planktotrophy. These changes were even more pronounced within the GRN than across the transcriptome as a whole, and occurred in each network territory (skeletogenic, endomesoderm and ectoderm). I found evidence for both conservation and divergence of regulatory interactions in the network, as well as significant changes in the expression of genes with known roles in larval skeletogenesis, which is dramatically altered in lecithotrophs. I further explored network dynamics between species using coexpression analyses, which allowed me to identify novel players likely involved in sea urchin neurogenesis and endoderm patterning.

In Chapter 3, I investigate developmental changes in gene expression underlying radial body plan development and metamorphosis in H. erythrogramma. Using Illumina RNA-seq, I measured gene expression profiles across larval, metamorphic, and post-metamorphic life cycle phases. My results present a high-resolution view of gene expression dynamics during the complex transition from pre- to post-metamorphic development and suggest that distinct sets of regulatory and effector proteins are used during different life history phases.

Collectively, my investigations provide an important foundation for future, empirical studies to investigate the functional role of gene expression change in the evolution of developmental differences between species and also for the generation of the unusual radial body plan of sea urchins.

Bordetella pertussis from functional genomics to intranasal vaccination.

Whooping cough still represents a major health problem, despite the use of effective vaccines for several decades. Being classically a typical childhood disease, whooping cough in young adults is now more common than it used to be, suggesting that protection after vaccination wanes during adolescence. As an alternative to the current vaccines, we wish to develop live attenuated vaccines to be delivered by the nasal route, such as to mimic the natural route of infection and to induce long lasting immunity. Bordetella pertussis, the etiological agent of whooping cough, produces a number of virulence factors, including toxins. Its recently determined genome sequence makes it now possible to apply functional genomics, such as transcriptomics and systematic knock-out mutagenesis. The expression of most known B. pertussis virulence genes is controlled by the two-component system BvgA/S. DNA microarray analyses have led to the identification of novel genes in the BvgA/S regulon, some of which are activated by BvgA/S and others are repressed by BvgA/S. In addition, some genes appear to be differentially modulated by nicotinic acid and MgSO4, both known to modulate the expression of BvgA/S-regulated genes. Among others, the functional genomics approach has uncovered two strongly BvgA/S-activated genes, named hotA and hotB (for 'homolog of toxin'), the products of which show high sequence similarities to pertussis toxin subunits. The identification of the full array of virulence factors, as well as an integrated understanding of the bacterial physiology should allow us to design attenuated B. pertussis strains useful for intranasal vaccination. A first generation of attenuated strains has already shown full protection in mice after a single intranasal administration. Such strains may also serve as vaccine carriers for heterologous antigens, in order to vaccinate against several different pathogens simultaneously.