Analysis of the ERK5 MAPK Signalling Pathway in Endothelial Cells

Angiogenesis is the development of new capillary vessels from pre-existing ones. It involves the proliferation, migration and differentiation of endothelial cells. It is activated by different stimuli and requires the coordination of several signalling pathways. The most important growth factor for angiogenesis is VEGF. However, other factors also play an important role. For example, H2S is a gaseous molecule that exerts its pro-angiogenic effect through activation of the pro-survival Akt signalling pathway. In vitro studies have further shown the ability of H2S to enhance endothelial cell proliferation, adhesion, migration, and tube formation. The ERK5 signalling cascade is the most recently discovered mammalian MAPK (mitogen-activated protein kinase) pathway. ERK5 knockout mice die due to impaired heart development and endothelial cell dysfunction. Furthermore, VEGF promotes ERK5 activation in primary endothelial cells and ERK5 is required for VEGF-induced tubular morphogenesis. Importantly, VEGF activates ERK5 in endothelial cells, which in turn activates the AKT pro-survival pathway to suppress apoptosis of endothelial cells. As H2S also mediates its vasoprotective effect through AKT activation, the hypothesis of this thesis was that H2S protects endothelial cells by activating the ERK5 pathway. The aim of this thesis was therefore to investigate whether H2S activates ERK5 and to develop the necessary tools to further investigate the mechanisms involved. In this thesis, an assay detecting and quantifying an electrophoretic mobility shift by western blotting has been developed to measure ERK5 activation in mammalian cells. Furthermore, ERK5 could be shown to be activated by H2S in HeLa cells. Importantly, H2S also activated ERK5 in endothelial cells, demonstrating that ERK5 signalling mediates the pro-survival response of H2S in endothelial cells. To further analyse ERK5 activation in response to various stimuli, including H2S, additional tools to determine ERK5 phosphorylation were evaluated, including mass spectrometric determination of phosphorylation sites and the characterisation of a novel phosphor-specific antibody

Influence of Emotionality on Discourse Production in Aphasia: A Stimulus Validation Study

The purpose of this study was to validate experimental video stimuli designed to examine the influence of emotionality on discourse produced by Arabic speakers with aphasia. Ten healthy Arabic speakers described events depicted in 15 videos within three emotional categories: positive, negative, and neutral. Participants responded to a questionnaire judging the videos on three emotion dimensions, logical sequence, and interest. Elicited discourse was analyzed for content units. Results of the questionnaire and content unit analysis were instrumental in selecting a subset of nine videos used in investigating discourse production in aphasia. Results also predicted performance in the aphasia study

Smart Operations of Air-Conditioning and Lighting Systems in a Government Buildings for Peak Power Reduction

This paper presents the achievements of implementing smart operations strategies for air-conditioning (A/C) and lighting systems in Justice Palace Complex (JPC), Kuwait during the summer 2007. The peak load of this building was 3700 kW. The achievements are summarized as direct savings between 13:00 and 22:00 h by closing supply and return air fans of 52 air-handling units with a connected load 400 kW, and an additional saving of 550 kW during the same period by optimizing the cooling production and distribution. Also an all time saving of 22 kW by de-lamping, and additional saving of 27 kW through TDC of lighting were achieved. In conclusion project achieved an overall reduction in power demand of around 20% between 13:00 to 17:00 h and reduction ranging from 7% to 15% between 17:00 to 20:00 h

Cost Effectiveness for Solar Control Film for Residential Applications

For the existing housing, retrofitting single or double glazed clear glass window with solar films can be an effective measure to reduce their peak power demand, and large scale application of the same on national level can be an effective tool for demand side management. This paper analyses the field performance data of a solar control film, retrofitted in a Kuwait villa, for establishing its technical viability and cost effectiveness. The paper concludes that the solar film, besides enhancing the thermal comfort, reduced the peak cooling demand and the peak power demand by 6.7% and 4.7%, respectively, during the peak summer period

Improving the Water Efficiency of Cooling Production System

For most of the time, cooling towers (CTs) of cooling systems operate under partial load conditions and by regulating the air circulation with a variable frequency drive (VFD), significant reduction in the fan power can be achieved. In Kuwait and other counties of Arabian Peninsula, reduced airflow can lead to reduction in water consumption as well, since during the summer season, the dry bulb temperature of the ambient air is higher than the incoming hot water temperature, and the air undergoes sensible cooling. This paper presents the findings of a study conducted in the Avenues mall, Kuwait. Initially, the CTs operated only at high speed, and on a typical summer day nearly one fourth of the make-up water was used for self cooling of air. The study based on measured data revealed that the use of VFD can reduce the water wastage for self-cooling of air by as much as 75% and overall water consumption by 18.6% while keeping the cooling system performance at design level

Smart Operations of Air-Conditioning and Lighting Systems in a Government Buildings for Peak Power Reduction

This paper presents the achievements of implementing smart operations strategies for air-conditioning (A/C) and lighting systems in Justice Palace Complex (JPC), Kuwait during the summer 2007. The peak load of this building was 3700 kW. The achievements are summarized as direct savings between 13:00 and 22:00 h by closing supply and return air fans of 52 air-handling units with a connected load 400 kW, and an additional saving of 550 kW during the same period by optimizing the cooling production and distribution. Also an all time saving of 22 kW by de-lamping, and additional saving of 27 kW through TDC of lighting were achieved. In conclusion project achieved an overall reduction in power demand of around 20% between 13:00 to 17:00 h and reduction ranging from 7% to 15% between 17:00 to 20:00 h

Smart Operations of Air-Conditioning and Lighting Systems in Government Buildings for Peak Power Reduction

During the summer 2007 smart operation strategies for air-conditioning (A/C) and lighting systems were developed and tested in a number of governmental buildings in Kuwait as one of the solutions to reduce the national peak demand for electrical power that commonly occur around 15:00 h. The working hours for these building are generally between 07:00 and 14:00 h and their peak demand exceeds 600 MW. The smart operation strategies implemented in these buildings included pre-closing treatment (PCT) between 13:00 and 14:00 h and time-of-day control (TDC) after 14:00 h. Also de-lamping was carried out in some of the buildings to readjust the higher than recommended illumination levels. This paper presents the achievements of implementing these smart operations strategies in Justice Palace Complex (JPC) as a case study. The peak load of this building was 3700 kW. The achievements are summarized as an all time saving of 22 kW by de-lamping, an additional saving of 27 kW through TDC of lighting, direct savings between 13:00 and 22:00 h by closing supply and return air fans of 52 air-handling units with a connected load 400 kW, and an additional saving of 550 kW during the same period by optimizing the cooling production and distribution. In conclusion project achieved an overall reduction in power demand of around 20% between 13:00 to 17:00 h and reduction ranging from 7% to 15% between 17:00 to 20:00 h

Implementation of Energy and Power Saving Scheme in The Avenues Mall

This paper presents the results on an energy audit and subsequent implementation of energy efficient operation and maintenance strategies between April 2008 and March 2009 in Phase 1 of the Avenues mall with total area of 170,000 m2. It has cooling production system with a capacity of 7200 RT and prior to energy audit, its peak power demand was close to 15 MW and annual energy consumption was 84000 MWh/y. Overall reductions of 9919 MWh/y in the annual energy consumption and 345 kW in peak power demand were achieved. The major contributors for the savings were time-of-day control for the air-handling units and lighting and optimization of chilled water flow. The project facilitated a benefit of 19838 KD/y to the Mabanee and company. More importantly, it achieved financial benefits to the Ministry of Electricity and Water of nearly 160,000 KD for reduction in power generation and transmission equipment cost and 372000 KD/y towards reduction in annual electricity subsidy in addition to an environmental benefit of reduction in CO2 emissions by 6940 t/y

Influence of emotionality on pragmatic features of discourse produced by Arabic-speaking adults with aphasia

A review of the literature indicates a facilitative effect of emotional content on communicative abilities in aphasia, including discourse production (e.g., Bloom, Borod, Obler, & Gerstman, 1992; Bloom, Borod, Santschi-Haywood, Pick, & Obler, 1996; Landis, Graves, & Goodglass, 1982; Ramsberger, 1979; Reuterskioeld, 1991). To explore how emotional content influences discourse-level pragmatic features in narratives produced by Arabic-speaking adults with aphasia, Grice's (1975) pragmatic framework for discourse analysis was adopted. The primary question addressed by the current study was whether or not discourse elicited using stimuli with emotional content (positive or negative) is superior in quantity, quality, relevance, and manner than that elicited using non-emotional content (neutral) in an aphasia group and a healthy group of adults.Two experiments were conducted. The first experiment was designed to determine the appropriateness of the testing stimuli---a set of video-clips that had been purposefully constructed for this study. The goal was to ensure that each video-clip met specific requirements with regard to valence category, emotional intensity, logical sequence, and interest level. A group of young healthy adults narrated the events portrayed in the clips and completed an emotionality judgment questionnaire about the clips. Results of the stimulus validation experiment guided the selection of a subset of nine video-clips---three clips per emotional category: positive, negative, and neutral---that were utilized in the main experiment.In the main experiment, discourse was elicited from a group of adults with aphasia and normal controls using the video-clips. Samples were analyzed for pragmatic features using six measures: amount of production and communicative efficiency to assess discourse quantity; accuracy of production to assess discourse quality; coherence to assess discourse manner; and lexical selection and topic maintenance to assess discourse relevance. Results indicated that emotional content positively influenced performance on the majority of pragmatic variables. Results also revealed that adults with aphasia were less appropriate than normal controls on the majority of discourse measures under investigation. The findings are discussed in relation to current models of emotional, cognitive, and language processing