Multi-parametric metabolic assessment of cells under stress conditions

Glycolysis, glutaminolysis, the Krebs cycle and oxidative phosphorylation are the main metabolic pathways. Exposing cells to key metabolic substrates (glucose, glutamine and pyruvate); investigation of the contribution of substrates in stress conditions such as uncoupling and hypoxia was conducted. Glycolysis, O2 consumption, O2 and ATP levels and hypoxia inducible factor (HIF) signalling in PC12 cells were investigated. Upon uncoupling with FCCP mitochondria were depolarised similarly in all cases, but a strong increase in respiration was only seen in the cells fed on glutamine with either glucose or pyruvate. Inhibition of glutaminolysis reversed the glutamine dependant effect. Differential regulation of the respiratory response to FCCP by metabolic environment suggests mitochondrial uncoupling has a potential for substrate-specific inhibition of cell function. At reduced O2 availability (4 % and 0 % O2), cell bioenergetics and local oxygenation varied depending on the substrate composition. Results indicate that both supply and utilisation of key metabolic substrates can affect the pattern of HIF-1/2α accumulation by differentially regulating iO2¬, ATP levels and Akt/Erk/AMPK pathways. Inhibition of key metabolic pathways can modulate HIF regulatory pathways, metabolic responses and survival of cancer cells in hypoxia. Hypoxia leads to transcriptional activation, by HIF, of pyruvate dehydrogenase (PDH) kinase which phosphorylates and inhibits PDH, a mitochondrial enzyme that converts pyruvate into acetyl-CoA. The levels of PDH (total and phosphorylated), PDH kinase and HIF-1α were analysed in HCT116 and HCT116 SCO2-/- (deficient in complex IV of the respiratory chain) grown under 20.9 % and 3 % O2. Data indicate that regulation of PDH can occur in a manner independent of the HIF-1/PDH kinase 1 axis, mitochondrial respiration and the demand for acetyl-CoA. Collectively these results can be applied to many diseases; reduced nutrient supply and O2 during ischemia/stroke, hypoglycaemia in diabetes mellitus and cancer associated changes in uncoupling protein expression levels.

A cycle route planner mobile-app for Dublin city

In a road network, cyclists are the group exposed to the maximum amount of risk. Route choice of a cyclist is often based on level of expertise, perceived or actual road risks, personal decisions, weather conditions and a number of other factors. Consequently, cycling tends to be the only significant travel mode where optimised route choice is not based on least-path or least-time. This paper presents an Android platform based mobile-app for personalised route planning of cyclists in Dublin. The mobile-app, apart from its immediate advantage to the cyclists, acts as the departure point for a number of research projects and aids in establishing some critical calibration values for the cycling network in Dublin. 

Building effectiveness communication ratios (BECs): an integrated ‘life-cycle’ methodology for mitigating energy-use in buildings

Current building regulations are generally prescriptive in nature. It is widely accepted in Europe that this form of building regulation is stifling technological innovation and leading to inadequate energy efficiency in the building stock. This has increased the motivation to move design practices towards a more ‘performance-based’ model in order to mitigate inflated levels of energy-use consumed by the building stock. A performance based model assesses the interaction of all building elements and the resulting impact on holistic building energy-use. However, this is a nebulous task due to building energy-use being affected by a myriad of heterogeneous agents. Accordingly, it is imperative that appropriate methods, tools and technologies are employed for energy prediction, measurement and evaluation throughout the project’s life cycle. This research also considers that it is imperative that the data is universally accessible by all stakeholders. The use of a centrally based product model for exchange of building information is explored. This research describes the development and implementation of a new building energy-use performance assessment methodology. Termed the Building Effectiveness Communications ratios (BECs) methodology, this performance-based framework is capable of translating complex definitions of sustainability for energy efficiency and depicting universally understandable views at all stage of the Building Life Cycle (BLC) to the project’s stakeholders. The enabling yardsticks of building energy-use performance, termed Ir and Pr, provide continuous design and operations feedback in order to aid the building’s decision makers. Utilised effectively, the methodology is capable of delivering quality assurance throughout the BLC by providing project teams with quantitative measurement of energy efficiency. Armed with these superior enabling tools for project stakeholder communication, it is envisaged that project teams will be better placed to augment a knowledge base and generate more efficient additions to the building stock.

A knowledge management system to optimise comfort throughout the building life-cycle

Comfort is, in essence, satisfaction with the environment, and with respect to the indoor environment it is primarily satisfaction with the thermal conditions and air quality. Improving comfort has social, health and economic benefits, and is more financially significant than any other building cost. Despite this, comfort is not strictly managed throughout the building lifecycle. This is mainly due to the lack of an appropriate system to adequately manage comfort knowledge through the construction process into operation. Previous proposals to improve knowledge management have not been successfully adopted by the construction industry. To address this, the BabySteps approach was devised. BabySteps is an approach, proposed by this research, which states that for an innovation to be adopted into the industry it must be implementable through a number of small changes. This research proposes that improving the management of comfort knowledge will improve comfort. ComMet is a new methodology proposed by this research that manages comfort knowledge. It enables comfort knowledge to be captured, stored and accessed throughout the building life-cycle and so allowing it to be re-used in future stages of the building project and in future projects. It does this using the following: Comfort Performances – These are simplified numerical representations of the comfort of the indoor environment. Comfort Performances quantify the comfort at each stage of the building life-cycle using standard comfort metrics. Comfort Ratings - These are a means of classifying the comfort conditions of the indoor environment according to an appropriate standard. Comfort Ratings are generated by comparing different Comfort Performances. Comfort Ratings provide additional information relating to the comfort conditions of the indoor environment, which is not readily determined from the individual Comfort Performances. Comfort History – This is a continuous descriptive record of the comfort throughout the project, with a focus on documenting the items and activities, proposed and implemented, which could potentially affect comfort. Each aspect of the Comfort History is linked to the relevant comfort entity it references. These three components create a comprehensive record of the comfort throughout the building lifecycle. They are then stored and made available in a common format in a central location which allows them to be re-used ad infinitum. The LCMS System was developed to implement the ComMet methodology. It uses current and emerging technologies to capture, store and allow easy access to comfort knowledge as specified by ComMet. LCMS is an IT system that is a combination of the following six components: Building Standards; Modelling & Simulation; Physical Measurement through the specially developed Egg-Whisk (Wireless Sensor) Network; Data Manipulation; Information Recording; Knowledge Storage and Access.Results from a test case application of the LCMS system - an existing office room at a research facility - highlighted that while some aspects of comfort were being maintained, the building’s environment was not in compliance with the acceptable levels as stipulated by the relevant building standards. The implementation of ComMet, through LCMS, demonstrates how comfort, typically only considered during early design, can be measured and managed appropriately through systematic application of the methodology as means of ensuring a healthy internal environment in the building.