Pregnancy-specific glycoprotein function, conservation and receptor investigation

Pregnancy-specific glycoproteins (PSGs) are highly glycosylated secreted proteins encoded by multi-gene families in some placental mammals. They are carcinoembryonic antigen (CEA) family and immunoglobulin (Ig) superfamily members. PSGs are immunomodulatory, and have been demonstrated to possess antiplatelet and pro-angiogenic properties. Low serum levels of these proteins have been correlated with adverse pregnancy outcomes. Objectives: Main research goals of this thesis were: 1). To attempt to replicate previously reported cytokine responses to PSG-treatment of immune cells and subsequently to investigate functionally important amino acids within PSG1. 2). To determine whether candidate receptor, integrin αvβ3, was a binding partner for PSG1 and to investigate whether PSG1 possessed functionality in a leukocyte-endothelial interaction assay. 3). To determine whether proteins generated from recently identified putative PSG genes in the horse shared functional properties with PSGs from other species. Outcomes: 1). Sequential domain deletion of PSG1 as well as mutation of conserved residues within the PSG1 Ndomain did not affect PSG1-induced TGF-β1. The investigated response was subsequently found to be the result of latent TGF-β1 contaminating the recombinant protein. Protein further purified by SEC to remove this showed no induction of TGF-β1. The most N-terminal glycosylation site was demonstrated to have an important role in PSG N domain secretion. PSG1 attenuated LPS-induced IL-6 and TNF-α. Investigations into signalling underpinning this proved inconclusive. 2). Integrin αvβ3 was identified as a novel PSG1 receptor mediating an as yet unknown function. Preliminary investigations into a role for PSGs as inhibitors of leukocyte endothelial interactions showed no effect by PSG1. 3). Horse PSG protein, CEACAM49, was shown to be similarly contaminated by latent TGF-β1 particle and once removed did not demonstrate TGF-β1 release. Interestingly horse PSG did show anti-platelet properties through inhibition of the plateletfibrinogen interaction as previously published for mouse and human PSGs.

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.

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.