Functional genomic hypothesis generation and experimentation by a robot scientist

King R. D., Whelan, K. E., Jones, F. M., Reiser, P. G. K., Bryant, C. H., Muggleton, S., Kell, D. B. and Oliver, S. G. (2004) Functional genomic hypothesis generation and experimentation by a robot scientist. Nature 427 (6971) p247-252

Machine learning of functional class from phenotype data

Clare, A. and King R.D. (2002) Machine learning of functional class from phenotype data. Bioinformatics 18(1) 160-166

Staged Competence Learning in Developmental Robotics

M.H. Lee, Q. Meng and F. Chao, 'Staged Competence Learning in Developmental Robotics', Adaptive Behavior, 15(3), pp 241-255, 2007. the full text will be available in September 2008

Locational distribution of gene functional classes in Arabidopsis thaliana

Riley, M. C., Clare, A., King, R. D. (2007). Locational distribution of gene functional classes in Arabidopsis thaliana. BMC Bioinformatics 8, Article No: 112 Sponsorship: EPSRC / RAEng

Jurisdiction and the Internet: Regulatory Competence over Online Activity

null RAE2008

Brachypodium distachyon. A new model system for functional genomics in grasses

John Draper, Luis A.J. Mur, Glyn Jenkins, Gadab C. Ghosh-Biswas, Pauline Bablak, Robert Hasterok,and Andrew P.M. Routledge (2001). Brachypodium distachyon. A new model system for functional genomics in grasses. Plant Physiology, 127 (4), 1539-1555. Sponsorship: BBSRC / Gatsby Foundation RAE2008

A Pragmatic Approach to DHT Adoption

Despite the peer-to-peer community's obvious wish to have its systems adopted, specific mechanisms to facilitate incremental adoption have not yet received the same level of attention as the many other practical concerns associated with these systems. This paper argues that ease of adoption should be elevated to a first-class concern and accordingly presents HOLD, a front-end to existing DHTs that is optimized for incremental adoption. Specifically, HOLD is backwards-compatible: it leverages DNS to provide a key-based routing service to existing Internet hosts without requiring them to install any software. This paper also presents applications that could benefit from HOLD as well as the trade-offs that accompany HOLD. Early implementation experience suggests that HOLD is practical.

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.

Lightweight Formal Verification in Classroom Instruction of Reasoning about Functional Code

In college courses dealing with material that requires mathematical rigor, the adoption of a machine-readable representation for formal arguments can be advantageous. Students can focus on a specific collection of constructs that are represented consistently. Examples and counterexamples can be evaluated. Assignments can be assembled and checked with the help of an automated formal reasoning system. However, usability and accessibility do not have a high priority and are not addressed sufficiently well in the design of many existing machine-readable representations and corresponding formal reasoning systems. In earlier work [Lap09], we attempt to address this broad problem by proposing several specific design criteria organized around the notion of a natural context: the sphere of awareness a working human user maintains of the relevant constructs, arguments, experiences, and background materials necessary to accomplish the task at hand. We report on our attempt to evaluate our proposed design criteria by deploying within the classroom a lightweight formal verification system designed according to these criteria. The lightweight formal verification system was used within the instruction of a common application of formal reasoning: proving by induction formal propositions about functional code. We present all of the formal reasoning examples and assignments considered during this deployment, most of which are drawn directly from an introductory text on functional programming. We demonstrate how the design of the system improves the effectiveness and understandability of the examples, and how it aids in the instruction of basic formal reasoning techniques. We make brief remarks about the practical and administrative implications of the system’s design from the perspectives of the student, the instructor, and the grader.

Neuropeptide Co-Release with Gaba May Explain Functional Non-Monotonic Uncertainty Responses in Dopamine Neurons

Co-release of the inhibitory neurotransmitter GABA and the neuropeptide substance-P (SP) from single axons is a conspicuous feature of the basal ganglia, yet its computational role, if any, has not been resolved. In a new learning model, co-release of GABA and SP from axons of striatal projection neurons emerges as a highly efficient way to compute the uncertainty responses that are exhibited by dopamine (DA) neurons when animals adapt to probabilistic contingencies between rewards and the stimuli that predict their delivery. Such uncertainty-related dopamine release appears to be an adaptive phenotype, because it promotes behavioral switching at opportune times. Understanding the computational linkages between SP and DA in the basal ganglia is important, because Huntington's disease is characterized by massive SP depletion, whereas Parkinson's disease is characterized by massive DA depletion.

Market-oriented new product development of functional beverages

Strategic reviews of the Irish Food and Beverage Industry have consistently emphasised the need for food and beverage firms to improve their innovation and marketing capabilities, in order to maintain competitiveness in both domestic and overseas markets. In particular, the functional food and beverages market has been singled out as an extremely important emerging market, which Irish firms could benefit from through an increased technological and market orientation. Although health and wellness have been the most significant drivers of new product development (NPD) in recent years, failure rates for new functional foods and beverages have been reportedly high. In that context, researchers in the US, UK, Denmark and Ireland have reported a marked divergence between NPD practices within food and beverage firms and normative advice for successful product development. The high reported failure rates for new functional foods and beverages suggest a failure to manage customer knowledge effectively, as well as a lack of knowledge management between functional disciplines involved in the NPD process. This research explored the concept of managing customer knowledge at the early stages of the NPD process, and applied it to the development of a range of functional beverages, through the use of advanced concept optimisation research techniques, which provided for a more market-oriented approach to new food product development. A sequential exploratory research design strategy using mixed research methods was chosen for this study. First, the qualitative element of this research investigated customers’ choice motives for orange juice and soft drinks, and explored their attitudes and perceptions towards a range of new functional beverage concepts through a combination of 15 in-depth interviews and 3 focus groups. Second, the quantitative element of this research consisted of 3 conjoint-based questionnaires administered to 400 different customers in each study in order to model their purchase preferences for chilled nutrient-enriched and probiotic orange juices, and stimulant soft drinks. The in-depth interviews identified the key product design attributes that influenced customers’ choice motives for orange juice. The focus group discussions revealed that groups of customers were negative towards the addition of certain functional ingredients to natural foods and beverages. K-means cluster analysis was used to quantitatively identify segments of customers with similar preferences for chilled nutrient-enriched and probiotic orange juices, and stimulant soft drinks. Overall, advanced concept optimisation research methods facilitate the integration of the customer at the early stages of the NPD process, which promotes a multi-disciplinary approach to new food product design. This research illustrated how advanced concept optimisation research methods could contribute towards effective and efficient knowledge management in the new food product development process.

The differences in the social competence of children who attend integrated junior infant classes and children who attend segregated learning environments

There are a number of reasons why this researcher has decided to undertake this study into the differences in the social competence of children who attend integrated Junior Infant classes and children who attend segregated learning environments. Theses reasons are both personal and professional. My personal reasons stem from having grown up in a family which included both an aunt who presented with Down Syndrome and an uncle who presented with hearing impairment. Both of these relatives' experiences in our education system are interesting. My aunt was considered ineducable while her brother - my uncle - was sent to Dublin (from Cork) at six years of age to be educated by a religious order. My professional reasons, on the other hand, stemmed from my teaching experience. Having taught in both special and integrated classrooms it became evident to me that there was somewhat 'suspicion' attached to integration. Parents of children without disabilities questioned whether this process would have a negative impact on their children's education. While parents of children with disabilities debated whether integrated settings met the specific needs of their children. On the other hand, I always questioned whether integration and inclusiveness meant the same thing. My research has enabled me to find many answers. Increasingly, children with special educational needs (SEN) are attending a variety of integrated and inclusive childcare and education settings. This contemporary practice of educating children who present with disabilities in mainstream classrooms has stimulated vast interest on the impact of such practices on children with identified disabilities. Indeed, children who present with disabilities "fare far better in mainstream education than in special schools" (Buckley, cited in Siggins, 2001,p.25). However, educators and practitioners in the field of early years education and care are concerned with meeting the needs of all children in their learning environments, while also upholding high academic standards (Putman, 1993). Fundamentally, therefore, integrated education must also produce questions about the impact of this practice on children without identified special educational needs. While these questions can be addressed from the various areas of child development (i.e. cognitive, physical, linguistic, emotional, moral, spiritual and creative), this research focused on the social domain. It investigates the development of social competence in junior infant class children without identified disabilities as they experience different educational settings.

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.

Nutraceutical and functional food bioactive peptides in beef

In recent years, the potential to positively modulate human health through dietary approaches has received considerable attention. Bioactive peptides which are released during the hydrolysis or fermentation of food proteins or following digestion may exert beneficial physiological effects in vivo. The aim of this work was to isolate, characterise and evaluate Angiotensin-І-converting enzyme (ACE-І) inhibitory, antimicrobial and antioxidant peptides from the bovine myofibrillar proteins actin and myosin. In order to generate these peptides, the myofibrillar proteins actin and myosin were hydrolysed with digestive enzymes pepsin, trypsin and α-chymotrypsin, or with the industrial thermolysin-like enzyme “Thermoase”, Amano Inc. It was found that each hydrolysate generated contained peptides which possessed ACE inhibitory, antioxidant and antimicrobial activity. The peptides responsible in part for the observed ACE inhibitory, antioxidant and antimicrobial activity of a number of hydrolysates were isolated using the method of RP-HPLC and the bioactive peptides contained within each active fraction was determined using either MALDI-TOF MS/MS or N-terminal peptide sequencing. During the course of this thesis six ACE inhibitory and five antimicrobial peptides were identified. It was determined that the reported antioxidant activity was a direct result of a number of peptides working in synergy with each other. The IC50 values of the six ACE inhibitory peptides ranged in values of 6.85 to 75.7 µM which compare favourably to values previously reported for other food derived ACE inhibitory peptides, particularly the well known milk peptides IPP and VPP, IC50 values of 5 and 9 µM respectively. All five antimicrobial peptides identified in this thesis displayed activity against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus and Listeria innocua with MIC values ranging from 0.625 to10 mM. The activity of each antimicrobial peptide was strain specific. Furthermore the role and importance of charged amino acids to the activity of antimicrobial peptides was also determined. Generally the removal of charged amino acids from the sequence of antimicrobial peptides resulted in a loss of antimicrobial activity. In conclusion, this thesis revealed that a range of bioactive peptides exhibiting ACE inhibitory, antioxidant and antimicrobial activities were encrypted in bovine myofibrillar proteins that could be released using digestive and industrial enzymes. Finally enzymatic hydrolysates of muscle proteins could potentially be incorporated into functional foods; however, the potential health benefits would need to be proven in human clinical studies.

Functional genomics of commensal Lactobacilli

Catabolic flexibility affords a bacterium the ability to utilise different sugar sources as carbon for energy. This is important for commensal lactobacilli like Lactobacillus ruminis which can be exposed to a variety of carbohydrates in vivo. However, little is known about the fermentation capabilities, metabolic pathways, genetic diversity or potential survival mechanisms used by L. ruminis in vivo. A combination of in vitro and in silico techniques was used to identify the catabolic pathways of L. ruminis. I also compared 16 L. ruminis strains using a panel of biochemical and survival assays, genetically, whole genome sequencing and RNA sequencing. Multi locus sequence typing revealed that strains clustered according to their host sources. Transcriptome analysis by RNAseq of two motile strains under three growth conditions, including swarming, identified the up-regulation of carbohydrate-related genes under swarming conditions. This suggests that carbohydrate flexibility may have an uncharacterised role in L. ruminis swarming. Following on from the assessment of L. ruminis catabolic flexibility, the porcine diet was supplemented with galactooligosaccharides or L. ruminis ATCC 25644 plus galactooligosaccharides. Supplementation of the porcine diet with galactooligosaccharide had no effect on microbiota diversity. In contrast, the L. ruminis plus galactooligosaccharide treatment significantly reduced the microbiota diversity. Diet is a major factor that affects the diversity of the gut microbiota. In order to get a more thorough understanding of diet and gut health in animals such as racehorses and domesticated herbivores, I determined the core microbiota of animals consuming different feeds. Interestingly, the gut microbiota diversity correlated with the host phylogeny of the animal. The genome of Lactobacillus equi (2.19 Mb), isolated from a healthy Irish thoroughbred was also sequenced and annotated, and comprised 2,263 predicted genes. The large repertoire of predicted carbohydrate-related genes may offer L. equi an advantage in the complex and harsh hindgut environment. In summary, this thesis uses functional genomics to assess the effect that carbohydrates have on commensal lactobacilli and the microbiota as a whole.