Shh/Boc signaling is required for sustained generation of ipsilateral projecting ganglion cells in the mouse retina

Sonic Hedgehog (Shh) signaling is an important determinant of vertebrate retinal ganglion cell (RGC) development. In mice, there are two major RGC populations: (1) the Islet2-expressing contralateral projecting (c)RGCs, which both produce and respond to Shh; and (2) the Zic2-expressing ipsilateral projecting RGCs (iRGCs), which lack Shh expression. In contrast to cRGCs, iRGCs, which are generated in the ventrotemporal crescent (VTC) of the retina, specifically express Boc, a cell adhesion molecule that acts as a high-affinity receptor for Shh. In Boc −/− mutant mice, the ipsilateral projection is significantly decreased. Here, we demonstrate that this phenotype results, at least in part, from the misspecification of a proportion of iRGCs. In Boc−/− VTC, the number of Zic2-positive RGCs is reduced, whereas more Islet2/Shh-positive RGCs are observed, a phenotype also detected in Zic2 and Foxd1 null embryos.

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

Towards Fuzzy Compositional Modelling

X. Fu, Q. Shen and R. Zhao. 'Towards fuzzy compositional modelling,' In Proceedings of the 16th International Conference on Fuzzy Systems, 2007, pp. 1233-1238. Sponsorship: EPSRC

Data-driven fuzzy rule generation and its application for student academic performance evaluation

K. Rasmani and Q. Shen. Data-driven fuzzy rule generation and its application for student academic performance evaluation. Applied Intelligence, 25(3):305-319, 2006.

A scenario-driven decision support system for serious crime investigation

Q. Shen, J. Keppens, C. Aitken, B. Schafer, and M. Lee. A scenario driven decision support system for serious crime investigation. Law, Probability and Risk, 5(2):87-117, 2006. Sponsorship: UK Engineering and Physical Sciences Research Council grant GR/S63267; partially supported by grant GR/S98603

Euro-Commentary : Scenario Analysis and Regional Economic Development: The Case of Mid Wales

Fuller-Love, Nerys, et al., 'Euro-Commentary : Scenario Analysis and Regional Economic Development: The Case of Mid Wales', European Urban and Regional Studies (2006) 13(2) pp.143-149 RAE2008

Entrepreneurship and rural economic development: a scenario analysis approach

Fuller-Love, N., Midmore, P., Thomas, D., Henley, A. (2006). Entrepreneurship and rural economic development: A scenario analysis approach. International Journal of Entrepreneurial Behaviour and Research, 12 (5), 289-305. RAE2008

Spontaneous DC Current Generation in a Resistively Shunted Semiconductor Superlattice Driven by a TeraHertz Field

We study a resistively shunted semiconductor superlattice subject to a high-frequency electric field. Using a balance equation approach that incorporates the influence of the electric circuit, we determine numerically a range of amplitude and frequency of the ac field for which a dc bias and current are generated spontaneously and show that this region is likely accessible to current experiments. Our simulations reveal that the Bloch frequency corresponding to the spontaneous dc bias is approximately an integer multiple of the ac field frequency.

Fractional and unquantized dc voltage generation in THz-driven semiconductor superlattices

We consider the spontaneous creation of a dc voltage across a strongly coupled semiconductor superlattice subjected to THz radiation. We show that the dc voltage may be approximately proportional either to an integer or to a half- integer multiple of the frequency of the applied ac field, depending on the ratio of the characteristic scattering rates of conducting electrons. For the case of an ac field frequency less than the characteristic scattering rates, we demonstrate the generation of an unquantized dc voltage.

BRITE: Universal Topology Generation from a User's Perspective

Effective engineering of the Internet is predicated upon a detailed understanding of issues such as the large-scale structure of its underlying physical topology, the manner in which it evolves over time, and the way in which its constituent components contribute to its overall function. Unfortunately, developing a deep understanding of these issues has proven to be a challenging task, since it in turn involves solving difficult problems such as mapping the actual topology, characterizing it, and developing models that capture its emergent behavior. Consequently, even though there are a number of topology models, it is an open question as to how representative the topologies they generate are of the actual Internet. Our goal is to produce a topology generation framework which improves the state of the art and is based on design principles which include representativeness, inclusiveness, and interoperability. Representativeness leads to synthetic topologies that accurately reflect many aspects of the actual Internet topology (e.g. hierarchical structure, degree distribution, etc.). Inclusiveness combines the strengths of as many generation models as possible in a single generation tool. Interoperability provides interfaces to widely-used simulation and visualization applications such as ns and SSF. We call such a tool a universal topology generator. In this paper we discuss the design, implementation and usage of the BRITE universal topology generation tool that we have built. We also describe the BRITE Analysis Engine, BRIANA, which is an independent piece of software designed and built upon BRITE design goals of flexibility and extensibility. The purpose of BRIANA is to act as a repository of analysis routines along with a user–friendly interface that allows its use on different topology formats.

Hierarchal Characterization and Generation of Blogosphere Workloads

We present a thorough characterization of the access patterns in blogspace, which comprises a rich interconnected web of blog postings and comments by an increasingly prominent user community that collectively define what has become known as the blogosphere. Our characterization of over 35 million read, write, and management requests spanning a 28-day period is done at three different levels. The user view characterizes how individual users interact with blogosphere objects (blogs); the object view characterizes how individual blogs are accessed; the server view characterizes the aggregate access patterns of all users to all blogs. The more-interactive nature of the blogosphere leads to interesting traffic and communication patterns, which are different from those observed for traditional web content. We identify and characterize novel features of the blogosphere workload, and we show the similarities and differences between typical web server workloads and blogosphere server workloads. Finally, based on our main characterization results, we build a new synthetic blogosphere workload generator called GBLOT, which aims at mimicking closely a stream of requests originating from a population of blog users. Given the increasing share of blogspace traffic, realistic workload models and tools are important for capacity planning and traffic engineering purposes.

Specification of optimum holistic building environmental and energy performance information to support informed decision making

Political drivers such as the Kyoto protocol, the EU Energy Performance of Buildings Directive and the Energy end use and Services Directive have been implemented in response to an identified need for a reduction in human related CO2 emissions. Buildings account for a significant portion of global CO2 emissions, approximately 25-30%, and it is widely acknowledged by industry and research organisations that they operate inefficiently. In parallel, unsatisfactory indoor environmental conditions have proven to negatively impact occupant productivity. Legislative drivers and client education are seen as the key motivating factors for an improvement in the holistic environmental and energy performance of a building. A symbiotic relationship exists between building indoor environmental conditions and building energy consumption. However traditional Building Management Systems and Energy Management Systems treat these separately. Conventional performance analysis compares building energy consumption with a previously recorded value or with the consumption of a similar building and does not recognise the fact that all buildings are unique. Therefore what is required is a new framework which incorporates performance comparison against a theoretical building specific ideal benchmark. Traditionally Energy Managers, who work at the operational level of organisations with respect to building performance, do not have access to ideal performance benchmark information and as a result cannot optimally operate buildings. This thesis systematically defines Holistic Environmental and Energy Management and specifies the Scenario Modelling Technique which in turn uses an ideal performance benchmark. The holistic technique uses quantified expressions of building performance and by doing so enables the profiled Energy Manager to visualise his actions and the downstream consequences of his actions in the context of overall building operation. The Ideal Building Framework facilitates the use of this technique by acting as a Building Life Cycle (BLC) data repository through which ideal building performance benchmarks are systematically structured and stored in parallel with actual performance data. The Ideal Building Framework utilises transformed data in the form of the Ideal Set of Performance Objectives and Metrics which are capable of defining the performance of any building at any stage of the BLC. It is proposed that the union of Scenario Models for an individual building would result in a building specific Combination of Performance Metrics which would in turn be stored in the BLC data repository. The Ideal Data Set underpins the Ideal Set of Performance Objectives and Metrics and is the set of measurements required to monitor the performance of the Ideal Building. A Model View describes the unique building specific data relevant to a particular project stakeholder. The energy management data and information exchange requirements that underlie a Model View implementation are detailed and incorporate traditional and proposed energy management. This thesis also specifies the Model View Methodology which complements the Ideal Building Framework. The developed Model View and Rule Set methodology process utilises stakeholder specific rule sets to define stakeholder pertinent environmental and energy performance data. This generic process further enables each stakeholder to define the resolution of data desired. For example, basic, intermediate or detailed. The Model View methodology is applicable for all project stakeholders, each requiring its own customised rule set. Two rule sets are defined in detail, the Energy Manager rule set and the LEED Accreditor rule set. This particular measurement generation process accompanied by defined View would filter and expedite data access for all stakeholders involved in building performance. Information presentation is critical for effective use of the data provided by the Ideal Building Framework and the Energy Management View definition. The specifications for a customised Information Delivery Tool account for the established profile of Energy Managers and best practice user interface design. Components of the developed tool could also be used by Facility Managers working at the tactical and strategic levels of organisations. Informed decision making is made possible through specified decision assistance processes which incorporate the Scenario Modelling and Benchmarking techniques, the Ideal Building Framework, the Energy Manager Model View, the Information Delivery Tool and the established profile of Energy Managers. The Model View and Rule Set Methodology is effectively demonstrated on an appropriate mixed use existing ‘green’ building, the Environmental Research Institute at University College Cork, using the Energy Management and LEED rule sets. Informed Decision Making is also demonstrated using a prototype scenario for the demonstration building.

High speed nonlinear optical components for next-generation optical communications

Electronic signal processing systems currently employed at core internet routers require huge amounts of power to operate and they may be unable to continue to satisfy consumer demand for more bandwidth without an inordinate increase in cost, size and/or energy consumption. Optical signal processing techniques may be deployed in next-generation optical networks for simple tasks such as wavelength conversion, demultiplexing and format conversion at high speed (≥100Gb.s-1) to alleviate the pressure on existing core router infrastructure. To implement optical signal processing functionalities, it is necessary to exploit the nonlinear optical properties of suitable materials such as III-V semiconductor compounds, silicon, periodically-poled lithium niobate (PPLN), highly nonlinear fibre (HNLF) or chalcogenide glasses. However, nonlinear optical (NLO) components such as semiconductor optical amplifiers (SOAs), electroabsorption modulators (EAMs) and silicon nanowires are the most promising candidates as all-optical switching elements vis-à-vis ease of integration, device footprint and energy consumption. This PhD thesis presents the amplitude and phase dynamics in a range of device configurations containing SOAs, EAMs and/or silicon nanowires to support the design of all optical switching elements for deployment in next-generation optical networks. Time-resolved pump-probe spectroscopy using pulses with a pulse width of 3ps from mode-locked laser sources was utilized to accurately measure the carrier dynamics in the device(s) under test. The research work into four main topics: (a) a long SOA, (b) the concatenated SOA-EAMSOA (CSES) configuration, (c) silicon nanowires embedded in SU8 polymer and (d) a custom epitaxy design EAM with fast carrier sweepout dynamics. The principal aim was to identify the optimum operation conditions for each of these NLO device configurations to enhance their switching capability and to assess their potential for various optical signal processing functionalities. All of the NLO device configurations investigated in this thesis are compact and suitable for monolithic and/or hybrid integration.

Generation and characterisation of biologically active milk-derived protein and peptide fractions

In recent years, extensive research has been carried out on the health benefits of milk proteins and peptides. Biologically active peptides are defined as specific protein fragments which have a positive impact on the physiological functions of the body; such peptides are produced naturally in vivo, but can also be generated by physical and/or chemical processes, enzymatic hydrolysis and/or microbial fermentation. The aims of this thesis were to investigate not only the traditional methods used for the generation of bioactive peptides, but also novel processes such as heat treatment, and the role of indigenous milk proteases, e.g., in mastitic milk, in the production of such peptides. In addition, colostrum was characterised as a source of bioactive proteins and peptides. Firstly, a comprehensive study was carried out on the composition and physical properties of colostrum throughout the early-lactation period. Marked differences in the physico-chemical properties of colostrum compared with milk were observed. Various fractions of colostrum were also tested for their effect on the secretion of pro- and anti-inflammatory cytokines from a macrophage cell line and bone marrow dendritic cells, as well as insulin secretion from a pancreatic beta cell line. A significant reduction in the secretion of the pro-inflammatory cytokines, TNF-α, IL-6, IL-1β and IL-12, a significant increase in the secretion of the anti-inflammatory cytokine, IL-10, as well as a significant increase in insulin secretion were observed for various colostrum fractions. Another study examined the early proteomic changes in the milk of 8 cows in response to infusion with the endotoxin lipopolysaccharide (LPS) at quarter level in a model mastitic system; marked differences in the protein and peptide profile of milk from LPS challenged cows were observed, and a pH 4.6-soluble fraction of this milk was found to cause a substantial induction in the secretion of IL-10 from a murine macrophage cell line. Heat-induced hydrolysis of sodium caseinate was investigated from the dual viewpoints of protein breakdown and peptide formation, and, a peptide fraction produced in this manner was found to cause a significant increase in the secretion of the anti-inflammatory cytokine, IL-10, from a murine macrophage cell line. The effects of sodium caseinate hydrolysed by chymosin on the gut-derived satiety hormone glucagon-like peptide-1 (GLP-1) were investigated; the resulting casein-derived peptides displayed good in vitro and in vivo secretion of GLP-1. Overall, the studies described in this thesis expand on current knowledge and provide good evidence for the use of novel methods for the isolation, generation and characterisation of bioactive proteins and/or peptides.