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Detailed simulation of the indoor environment to aid ventilation system design in low energy houses
No full textAccording to the International Energy Agency, buildings represent over one-third of total final energy consumption. Thus, a more sustainable future begins with low energy buildings which must combine comfort and function using passive systems and new evolving technologies. Policies to reduce building energy consumption and carbon emissions have been developed worldwide during the last decades. As a consequence, Building Regulations and Standards require more insulated and air tight buildings which may lead to indoor environment issues when the ventilation system is not designed appropriately or it is not used as designed. Poor Indoor Air Quality (IAQ) in low energy buildings is a concern, not only as a result of reduced ventilation rates, but also due to the increased number of materials used in modern building construction. These materials, together with cleaning products and occupants' activities, emit pollutants to the indoor environment and can lead to health problems.Detailed building modelling and simulation can provide an indication of building performance and furthermore, it can be used to assess indoor environment issues. This research is focused on the variability of overheating risk and poor IAQ at different locations in the building at different times. The impact that different pollutant sources and ventilation strategies has on the distribution of thermal comfort levels and IAQ in low-energy houses has been assessed through a modelling study using the detailed thermal simulation program, ESP-r. CO2 is commonly used as a proxy for IAQ, but a novelty of this research is the integrated analysis of distribution for other pollutants, specifically formaldehyde, PM2.5, PM10 and nitrogen dioxide. A model was created based on monitored data from a Passivhaus development in Scotland. Acceptance criteria for calibrating the model were defined, addressing the current absence of specific guidelines for model calibration based on the monitored indoor environment. Then, a review of current literature of indoor pollutants was undertaken and source emission models were implemented in ESP-r making use of the available published literature, with release rates as a function of the prevailing temperature and humidity. Different scenarios were defined to investigate specific design questions and common ventilation issues regarding the indoor environmental quality (IEQ). Ventilation regimes included natural ventilation, mechanical ventilation and mechanical ventilation with heat recovery options. These scenarios were compared in terms of energy demand, plus temporal and spatial variation of indoor environment metrics (thermal comfort and IAQ).The general conclusion arising from the analysis is that, contrary to the usual assumption of even distribution of the indoor environmental conditions, there can be significant variations in the internal distribution. Important factors are number and location of occupants and the movement of air within the building. The results demonstrate that detailed modelling and simulation can predict IEQ issues and help to design ventilation strategies in low energy houses. Although this study was focused on climate representative of conditions in Scotland, similar variations would be expected in other climates.According to the International Energy Agency, buildings represent over one-third of total final energy consumption. Thus, a more sustainable future begins with low energy buildings which must combine comfort and function using passive systems and new evolving technologies. Policies to reduce building energy consumption and carbon emissions have been developed worldwide during the last decades. As a consequence, Building Regulations and Standards require more insulated and air tight buildings which may lead to indoor environment issues when the ventilation system is not designed appropriately or it is not used as designed. Poor Indoor Air Quality (IAQ) in low energy buildings is a concern, not only as a result of reduced ventilation rates, but also due to the increased number of materials used in modern building construction. These materials, together with cleaning products and occupants' activities, emit pollutants to the indoor environment and can lead to health problems.Detailed building modelling and simulation can provide an indication of building performance and furthermore, it can be used to assess indoor environment issues. This research is focused on the variability of overheating risk and poor IAQ at different locations in the building at different times. The impact that different pollutant sources and ventilation strategies has on the distribution of thermal comfort levels and IAQ in low-energy houses has been assessed through a modelling study using the detailed thermal simulation program, ESP-r. CO2 is commonly used as a proxy for IAQ, but a novelty of this research is the integrated analysis of distribution for other pollutants, specifically formaldehyde, PM2.5, PM10 and nitrogen dioxide. A model was created based on monitored data from a Passivhaus development in Scotland. Acceptance criteria for calibrating the model were defined, addressing the current absence of specific guidelines for model calibration based on the monitored indoor environment. Then, a review of current literature of indoor pollutants was undertaken and source emission models were implemented in ESP-r making use of the available published literature, with release rates as a function of the prevailing temperature and humidity. Different scenarios were defined to investigate specific design questions and common ventilation issues regarding the indoor environmental quality (IEQ). Ventilation regimes included natural ventilation, mechanical ventilation and mechanical ventilation with heat recovery options. These scenarios were compared in terms of energy demand, plus temporal and spatial variation of indoor environment metrics (thermal comfort and IAQ).The general conclusion arising from the analysis is that, contrary to the usual assumption of even distribution of the indoor environmental conditions, there can be significant variations in the internal distribution. Important factors are number and location of occupants and the movement of air within the building. The results demonstrate that detailed modelling and simulation can predict IEQ issues and help to design ventilation strategies in low energy houses. Although this study was focused on climate representative of conditions in Scotland, similar variations would be expected in other climates
The role of mitogen-activated protein kinase phosphate-2 (MKP-2) in macrophage functions
Get PDFMitogen-activated protein kinase phosphatase-2 (MKP-2) is a type 1 nuclear dual specificity phosphatase which known to play key roles in cellular function through dephosphorylation of the MAPKs (ERK, JNK and p38). MKP-2 has recently been shown to play a significant role in the immune response following parasite and bacterial infections. However, the effect of MKP-2 deletion on a number of other key macrophages functions including phagocytosis, motility and proliferation is yet to be studied. This thesis therefore utilised a novel DUSP4 gene knockout mouse and investigated the effect of cellular MKP-2 removal in bone marrow derived macrophage (BMDMs) using a number of approaches.Results obtained from macrophage characterisation experiments demonstrated that following LPS stimulation MKP-2 deleted BMDMs showed enhanced JNK activation as opposed to other MAPKs, this effect was found to correlate with enhanced endothelin-1 (EDN1) expression at both gene and protein synthesis level. This is the first study to reveal that EDN1 expression is negatively regulated by MKP-2. MKP-2 deletion also resulted in different kinetic profiles for phagocytosis and migration which was also differed in M1 and M2 stimulated cultures. MKP-2-/- macrophages showed more phagocytic activity but less motility upon LPS activation, this effect was reversed when cells were pre-treated with IL-4 which gave less phagocytic activity but more motility. Also MKP-2 deletion reduced macrophage migration towards C5a suggesting a new role for MKP-2 gene in regulating macrophage motility. Loss of MKP-2 also resulted in decreased macrophage proliferation activity.Finally, a metabolomics profile was established for both MKP-2+/+ and MKP-2-/- macrophages stimulated by different agents. MKP-2 deletion resulted in enhanced production of metabolites associated with glycolysis and the pentose phosphate pathway during the time at which MAPKs were upregulated indicative of a tight correlation between signalling and metabolic changes that underlie macrophage functions. In contrast, the proline and arginine pathway was downregulated in MKP-2 deleted macrophages. This was confirmed by studying nitric oxide production which was downregulated in MKP-2-/- macrophages upon LPS challenge which further correlated with changes in citrulline and ornithine. Collectively, this is the first study to investigate and determine the role of MKP-2 gene in macrophage functions; deletion or inhibition of MKP-2 in macrophages may be a therapeutically desirable approach.Mitogen-activated protein kinase phosphatase-2 (MKP-2) is a type 1 nuclear dual specificity phosphatase which known to play key roles in cellular function through dephosphorylation of the MAPKs (ERK, JNK and p38). MKP-2 has recently been shown to play a significant role in the immune response following parasite and bacterial infections. However, the effect of MKP-2 deletion on a number of other key macrophages functions including phagocytosis, motility and proliferation is yet to be studied. This thesis therefore utilised a novel DUSP4 gene knockout mouse and investigated the effect of cellular MKP-2 removal in bone marrow derived macrophage (BMDMs) using a number of approaches.Results obtained from macrophage characterisation experiments demonstrated that following LPS stimulation MKP-2 deleted BMDMs showed enhanced JNK activation as opposed to other MAPKs, this effect was found to correlate with enhanced endothelin-1 (EDN1) expression at both gene and protein synthesis level. This is the first study to reveal that EDN1 expression is negatively regulated by MKP-2. MKP-2 deletion also resulted in different kinetic profiles for phagocytosis and migration which was also differed in M1 and M2 stimulated cultures. MKP-2-/- macrophages showed more phagocytic activity but less motility upon LPS activation, this effect was reversed when cells were pre-treated with IL-4 which gave less phagocytic activity but more motility. Also MKP-2 deletion reduced macrophage migration towards C5a suggesting a new role for MKP-2 gene in regulating macrophage motility. Loss of MKP-2 also resulted in decreased macrophage proliferation activity.Finally, a metabolomics profile was established for both MKP-2+/+ and MKP-2-/- macrophages stimulated by different agents. MKP-2 deletion resulted in enhanced production of metabolites associated with glycolysis and the pentose phosphate pathway during the time at which MAPKs were upregulated indicative of a tight correlation between signalling and metabolic changes that underlie macrophage functions. In contrast, the proline and arginine pathway was downregulated in MKP-2 deleted macrophages. This was confirmed by studying nitric oxide production which was downregulated in MKP-2-/- macrophages upon LPS challenge which further correlated with changes in citrulline and ornithine. Collectively, this is the first study to investigate and determine the role of MKP-2 gene in macrophage functions; deletion or inhibition of MKP-2 in macrophages may be a therapeutically desirable approach
Truxene based materials for organic electronics
Get PDFThis thesis was previously held under moratorium from 26th October 2018 until 26th October 2023.Organic electronics has become a major area of research interest over the last 20–30years. As society moves away from a reliance on fossil fuels, “cleaner energy”sources are being developed to complement existing avenues for energy, with onesuch source being organic photovoltaics. Additionally, as technology becomes moreubiquitous in everyday life, consumer expectations have driven advancements toimprove the resolution and lifetime of devices while reducing their energy consumption. One way this has manifested itself is with the advent of organic light emitting diode (OLED) displays. In both of these examples, conjugated organic molecules can provide the fundamental function of these organic semiconductor based devices. This thesis describes the synthesis and characterisation of several truxene based materials, which have potential application as interlayers within these devices. Initially, the influence of alkyl chain length was examined on a series of tricarboxylic acids. No significant change was observed in the optical and electrochemical properties; however the thermal properties and crystallographic packing were affected. While these molecules were found to be unsuitable for vacuum deposition, one of the intermediate materials (2.3) demonstrated templating ability. When included in organic photovoltaic devices, the performance was improved by the presence of this truxene interlayer. Following a short screen of reaction conditions, a hexaester (4.4) was prepared in high yields on a multigram scale. As a result of the extended conjugation present, this material exhibited a high PLQY in addition to strong π-π stacking in the crystal structure. Finally, two molecules with cyano containing functionalities were synthesised. These materials both exhibited pseudo-reversible oxidations, and one (5.2) a pseudo-reversible reduction. Additionally, solvatochromism was observed for compound 5.3.Organic electronics has become a major area of research interest over the last 20–30years. As society moves away from a reliance on fossil fuels, “cleaner energy”sources are being developed to complement existing avenues for energy, with onesuch source being organic photovoltaics. Additionally, as technology becomes moreubiquitous in everyday life, consumer expectations have driven advancements toimprove the resolution and lifetime of devices while reducing their energy consumption. One way this has manifested itself is with the advent of organic light emitting diode (OLED) displays. In both of these examples, conjugated organic molecules can provide the fundamental function of these organic semiconductor based devices. This thesis describes the synthesis and characterisation of several truxene based materials, which have potential application as interlayers within these devices. Initially, the influence of alkyl chain length was examined on a series of tricarboxylic acids. No significant change was observed in the optical and electrochemical properties; however the thermal properties and crystallographic packing were affected. While these molecules were found to be unsuitable for vacuum deposition, one of the intermediate materials (2.3) demonstrated templating ability. When included in organic photovoltaic devices, the performance was improved by the presence of this truxene interlayer. Following a short screen of reaction conditions, a hexaester (4.4) was prepared in high yields on a multigram scale. As a result of the extended conjugation present, this material exhibited a high PLQY in addition to strong π-π stacking in the crystal structure. Finally, two molecules with cyano containing functionalities were synthesised. These materials both exhibited pseudo-reversible oxidations, and one (5.2) a pseudo-reversible reduction. Additionally, solvatochromism was observed for compound 5.3
A critique of the approach of the gulf cooperation council states to choice of court agreements with reference to the 2005 Hague convention on choice of court agreements
Get PDFProper regulation of the recognition of choice of court agreements can provide significant advantages for the parties in international business transactions. Effective rules governing the recognition of choice of court agreements allow the parties to litigate before the court of their choice and may oblige a non-chosen court to decline jurisdiction in favour of the chosen court. Therefore, the recognition of choice of court agreements by national courts promotes legal certainty and predictability for the parties, avoids parallel litigation and inconsistent judgments and reduces litigation costs.;Choice of court agreements are a fundamental concept in private international law that seeks to ensure that the parties' expectations are met and that their intentions are fulfilled. In 2005, the approach to dealing with choice of court agreements, both at the litigation stage and at the recognition of foreign judgments stage in a commercial context, was harmonised by the global Hague Convention on Choice of Court Agreements, which entered into force on 1 October 2015 and is currently applicable in 31 countries. It seeks to ensure legal certainty and predictability between parties in international business transactions.;Even though the recognition of choice of court agreements is an important consideration in international business transactions, it will be demonstrated that the rules governing the recognition of choice of court agreements in the Gulf Cooperation Council States, which consist of Kuwait, The Kingdom of Saudi Arabia, the United Arab Emirates, Oman, The Kingdom of Bahrain and Qatar, are limited and problematic for the contracting parties and might not be conducive to facilitating and encouraging international business transactions.;Therefore, the underlying research question of this study considers the extent to which the current legal regimes for recognition of choice of court agreements in the GCC States is conducive to facilitating and encouraging international business in those States, by enabling the parties to avoid the risks of uncertainty and unpredictability, parallel litigation and inconsistent judgments in their international business transactions, and how the legal situation can be improved by ratifying the 2005 Hague Convention and by modernising their rules as they apply to choice of court agreements.Proper regulation of the recognition of choice of court agreements can provide significant advantages for the parties in international business transactions. Effective rules governing the recognition of choice of court agreements allow the parties to litigate before the court of their choice and may oblige a non-chosen court to decline jurisdiction in favour of the chosen court. Therefore, the recognition of choice of court agreements by national courts promotes legal certainty and predictability for the parties, avoids parallel litigation and inconsistent judgments and reduces litigation costs.;Choice of court agreements are a fundamental concept in private international law that seeks to ensure that the parties' expectations are met and that their intentions are fulfilled. In 2005, the approach to dealing with choice of court agreements, both at the litigation stage and at the recognition of foreign judgments stage in a commercial context, was harmonised by the global Hague Convention on Choice of Court Agreements, which entered into force on 1 October 2015 and is currently applicable in 31 countries. It seeks to ensure legal certainty and predictability between parties in international business transactions.;Even though the recognition of choice of court agreements is an important consideration in international business transactions, it will be demonstrated that the rules governing the recognition of choice of court agreements in the Gulf Cooperation Council States, which consist of Kuwait, The Kingdom of Saudi Arabia, the United Arab Emirates, Oman, The Kingdom of Bahrain and Qatar, are limited and problematic for the contracting parties and might not be conducive to facilitating and encouraging international business transactions.;Therefore, the underlying research question of this study considers the extent to which the current legal regimes for recognition of choice of court agreements in the GCC States is conducive to facilitating and encouraging international business in those States, by enabling the parties to avoid the risks of uncertainty and unpredictability, parallel litigation and inconsistent judgments in their international business transactions, and how the legal situation can be improved by ratifying the 2005 Hague Convention and by modernising their rules as they apply to choice of court agreements
Characterisation of novel compounds as antagonists of protease-activated receptor-2 (PAR2)
Get PDFProtease-activated receptor-2 (PAR2) is a G-protein coupled receptor that is activated through proteolytic cleavage of the N-terminus leading to the coupling to a number of defined second messenger systems though G-protein engagement. Early signalling events such as the mobilisation of intracellular Ca2+ and downstream cascades including ERK MAP kinase mediate an array of cellular effects stimulated through PAR2. Many studies have demonstrated the involvement of PAR2 in a number of disease pathologies including arthritis, GI disorders and inflammatory pain. However, treatments for these and other conditions have been limited by the lack of potent and selective small-molecule antagonists. Recently, a number of new putative antagonists including GB88 and AZ8838 have been proposed to be effective in cells and in vivo. However, given the relative lack of information about these compounds this thesis examined the characteristics of these compounds in a number of PAR2 mediated cellular assays.In Chapter 3 it was found that 2f-LIGRLO-NH2 and trypsin activated NFƙB-transcriptional activity in a PAR2 overexpressing cell line with potencies as expected from other studies.;Somewhat surprisingly, GB88 and a number of derivatives generated in-house, behaved as partial agonists compared to synthetic peptide 2f-LIGRLO-NH2 in stimulating reporter activity with reduced efficacy but moderate potency. They were largely ineffective as antagonists. In HEK293 where PAR2 expression was moderate, GB88 derivatives also stimulated the phosphorylation of ERK again with reduced efficacy and lower what compared with synthetic peptide. Moreover, intracellular calcium mobilisation mediated by PAR2 coupling to Gq/11 as determined by treatment with YM254890 was also activated by GB88 and related compounds with similar characteristics. In neither assay did GB88 act as a antagonist compound.Studies in chapter four examined the effect of the novel PAR2 antagonist, AZ8838 both as a racaemic mixture and as a pure compound. It was found to inhibit PAR2 induced NFƙB-transcriptional activity in NFƙB-Reporter cells in a concentration dependent manner confirming its identification as an allosteric modulator.;AZ8838 also decreased ERK and p38 MAP kinase stimulated by either 2f-LIGRLO-NH2 or trypsin in NFƙB-Reporter cells as well as inhibiting phosphorylation of ERK in HEK293 cells. In addition, AZ8838 had the ability to reduce PAR2-mediated calcium mobilisation in a time dependent fashion with maximum inhibition observed following preincubation for 30 minutes or more. These effects were consistent for the S-AZ8838 isomer whilst R-AZ8838 is not.Taking together these studies suggest that GB88 may have different pharamcological prpoerties in different systems but that AZ8838 has the potential to be a truly breakthrough compound. If the ADMET properties of AZ8838 are good this compound could be used in clincal studies for the treatment of inflammatroy disorders.Protease-activated receptor-2 (PAR2) is a G-protein coupled receptor that is activated through proteolytic cleavage of the N-terminus leading to the coupling to a number of defined second messenger systems though G-protein engagement. Early signalling events such as the mobilisation of intracellular Ca2+ and downstream cascades including ERK MAP kinase mediate an array of cellular effects stimulated through PAR2. Many studies have demonstrated the involvement of PAR2 in a number of disease pathologies including arthritis, GI disorders and inflammatory pain. However, treatments for these and other conditions have been limited by the lack of potent and selective small-molecule antagonists. Recently, a number of new putative antagonists including GB88 and AZ8838 have been proposed to be effective in cells and in vivo. However, given the relative lack of information about these compounds this thesis examined the characteristics of these compounds in a number of PAR2 mediated cellular assays.In Chapter 3 it was found that 2f-LIGRLO-NH2 and trypsin activated NFƙB-transcriptional activity in a PAR2 overexpressing cell line with potencies as expected from other studies.;Somewhat surprisingly, GB88 and a number of derivatives generated in-house, behaved as partial agonists compared to synthetic peptide 2f-LIGRLO-NH2 in stimulating reporter activity with reduced efficacy but moderate potency. They were largely ineffective as antagonists. In HEK293 where PAR2 expression was moderate, GB88 derivatives also stimulated the phosphorylation of ERK again with reduced efficacy and lower what compared with synthetic peptide. Moreover, intracellular calcium mobilisation mediated by PAR2 coupling to Gq/11 as determined by treatment with YM254890 was also activated by GB88 and related compounds with similar characteristics. In neither assay did GB88 act as a antagonist compound.Studies in chapter four examined the effect of the novel PAR2 antagonist, AZ8838 both as a racaemic mixture and as a pure compound. It was found to inhibit PAR2 induced NFƙB-transcriptional activity in NFƙB-Reporter cells in a concentration dependent manner confirming its identification as an allosteric modulator.;AZ8838 also decreased ERK and p38 MAP kinase stimulated by either 2f-LIGRLO-NH2 or trypsin in NFƙB-Reporter cells as well as inhibiting phosphorylation of ERK in HEK293 cells. In addition, AZ8838 had the ability to reduce PAR2-mediated calcium mobilisation in a time dependent fashion with maximum inhibition observed following preincubation for 30 minutes or more. These effects were consistent for the S-AZ8838 isomer whilst R-AZ8838 is not.Taking together these studies suggest that GB88 may have different pharamcological prpoerties in different systems but that AZ8838 has the potential to be a truly breakthrough compound. If the ADMET properties of AZ8838 are good this compound could be used in clincal studies for the treatment of inflammatroy disorders
The profitability of equity trading strategies
Get PDFClassification based on the attributes of firms' or stocks' performance is one of the commonly used methods in stock selection. This is known as style investing. This thesis examines three style investing techniques that classify stocks in different ways: (a) historical return based trading strategies, (b) value versus growth trading strategies, and (c) corporate solvency based trading strategies. In the context of these strategies this thesis aims to address two main research questions (a) can these trading strategies generate superior profits?, and (b) can risk, business cycles, and/or investors' sentiment explain the profitability of these strategies? The three-factor model by Fama and French (1993) is mainly used to control for risk. The investors' sentiment introduced by Baker and Wurgler (2006) and CLI index compiled by OECD are employed as the factors to investigate the role of investors' sentiment and business cycles, respectively. Chapter 2 of the thesis deals with the historical return based trading strategies. Under this criteria portfolios are formed on the basis of trends in historical returns. The two commonly used trading strategies that involve analysis of historical return trends are momentum and contrarian trading. Going long (short) on winnerstocks and short (long) on loser stocks is called momentum (contrarian) trading. Momentum profit is generated if the return from the strategy of going long on winnerstocks and short on loser stocks is positive (i.e. returns from long position minus returns from short position are positive). The findings of this thesis, however, do not provide evidence of momentum profit when conventional methods of momentum trading strategies are applied. On the other hand, if the returns from the strategy of going long on loser stocks and short on winner stocks (i.e. contrarian) are positive, then contrarian profit exists. The finding of this thesis provides evidence of contrarian profit in the short-horizon and long-horizon when conventional contrarian trading strategies are applied. When the three-factor model is applied to control for risk, the intercept is statistically significant. This suggests contrarian profits are not explained by risk. Similar results are found after incorporating the investors' sentiment factor into the model. This suggests contrarian profit exists even when controlling for both risk and investors' sentiment - contrarian profit cannot be explained by risk and investors' sentiment. This thesis also employs the residual trading strategies, which form portfolios on the basis of residual returns. The residual contrarian profit, however, cannot be observed when portfolios are formed on the basis of residual returns. In Chapter 3 this thesis examines whether strategies involving going long on value stocks and short on growth stocks generate superior returns. Value investors believe that value stocks are undervalued while growth stocks are overvalued but they should be correctly priced in the future, leading to excess returns. The value versus growth trading strategies are expected to generate profits, which are called value premiums. The findings of this thesis provide evidence that value premiums are persistently observed for all holding periods. The observed value premium exists even after controlling for risk, suggesting that the value premium is not driven by risk. A positive and significant coefficient of business cycle factor is observed after the business cycle factor is incorporated into the three-factor model (i.e. after controlling for risk).;This finding suggests that the value premium is positively driven by stages of the business cycle. The value premium, however, cannot be explained by investors' sentiment. At the industry level, the value premium of some industries (i.e. Consumer Durables, Manufacturing, Business Equipment, Shops, and Health) can be explained by stages of the business cycle. The relationship between value premium and investors' sentiment is consistent with the aggregate level, i.e.investors' sentiment is unable to explain the value premium of any of the industries. Finally, in Chapter 4 this thesis investigates if strategy that takes a long position on high solvency stocks and a short position on low solvency stocks can generate abnormal returns. Solvency is the ability of firms to cover their financial obligations. The high solvency firms are those firms with sufficient cash flows (orbalance) to cover their debt obligations while low solvency firms refer to firms that are unlikely to meet their debt obligations. The profitability of this strategy is called the solvency premium. The findings of this thesis show evidence of the solvency premium in the short-horizon but it reverts to solvency discount in the long-horizon. When the three-factor model is applied to control for risk, the solvency premium disappears. This suggests the solvency premium can be explained by risk. Further analysis, however, shows that after controlling for risk, the solvency premium exists in economic contraction and disappears during economic expansion. The solvency discount, inversely, is observed only during economic expansion. When the investors' sentiment factor is incorporated into the three-factor model, the positive and significant coefficient of investors' sentiment is observed. This suggests that investors' sentiment is also relevant in explaining solvency premium, i.e. high investors' sentiment leads to higher solvency premium. This thesis shows that three styles of investing techniques can generate superior returns (i.e. conventional contrarian trading strategy, value versus growthtrading strategies, and corporate solvency based trading strategy). However, momentum trading fails to generate any significant return. The findings benefit both individual and institutional investors to identify the stocks that are likely to generate superior returns and allocate their funds efficiently. These styles still exist until the market is more efficient relative to these styles and superior returns cannot be earned(Cao, 2011). These styles, then, disappear.Classification based on the attributes of firms' or stocks' performance is one of the commonly used methods in stock selection. This is known as style investing. This thesis examines three style investing techniques that classify stocks in different ways: (a) historical return based trading strategies, (b) value versus growth trading strategies, and (c) corporate solvency based trading strategies. In the context of these strategies this thesis aims to address two main research questions (a) can these trading strategies generate superior profits?, and (b) can risk, business cycles, and/or investors' sentiment explain the profitability of these strategies? The three-factor model by Fama and French (1993) is mainly used to control for risk. The investors' sentiment introduced by Baker and Wurgler (2006) and CLI index compiled by OECD are employed as the factors to investigate the role of investors' sentiment and business cycles, respectively. Chapter 2 of the thesis deals with the historical return based trading strategies. Under this criteria portfolios are formed on the basis of trends in historical returns. The two commonly used trading strategies that involve analysis of historical return trends are momentum and contrarian trading. Going long (short) on winnerstocks and short (long) on loser stocks is called momentum (contrarian) trading. Momentum profit is generated if the return from the strategy of going long on winnerstocks and short on loser stocks is positive (i.e. returns from long position minus returns from short position are positive). The findings of this thesis, however, do not provide evidence of momentum profit when conventional methods of momentum trading strategies are applied. On the other hand, if the returns from the strategy of going long on loser stocks and short on winner stocks (i.e. contrarian) are positive, then contrarian profit exists. The finding of this thesis provides evidence of contrarian profit in the short-horizon and long-horizon when conventional contrarian trading strategies are applied. When the three-factor model is applied to control for risk, the intercept is statistically significant. This suggests contrarian profits are not explained by risk. Similar results are found after incorporating the investors' sentiment factor into the model. This suggests contrarian profit exists even when controlling for both risk and investors' sentiment - contrarian profit cannot be explained by risk and investors' sentiment. This thesis also employs the residual trading strategies, which form portfolios on the basis of residual returns. The residual contrarian profit, however, cannot be observed when portfolios are formed on the basis of residual returns. In Chapter 3 this thesis examines whether strategies involving going long on value stocks and short on growth stocks generate superior returns. Value investors believe that value stocks are undervalued while growth stocks are overvalued but they should be correctly priced in the future, leading to excess returns. The value versus growth trading strategies are expected to generate profits, which are called value premiums. The findings of this thesis provide evidence that value premiums are persistently observed for all holding periods. The observed value premium exists even after controlling for risk, suggesting that the value premium is not driven by risk. A positive and significant coefficient of business cycle factor is observed after the business cycle factor is incorporated into the three-factor model (i.e. after controlling for risk).;This finding suggests that the value premium is positively driven by stages of the business cycle. The value premium, however, cannot be explained by investors' sentiment. At the industry level, the value premium of some industries (i.e. Consumer Durables, Manufacturing, Business Equipment, Shops, and Health) can be explained by stages of the business cycle. The relationship between value premium and investors' sentiment is consistent with the aggregate level, i.e.investors' sentiment is unable to explain the value premium of any of the industries. Finally, in Chapter 4 this thesis investigates if strategy that takes a long position on high solvency stocks and a short position on low solvency stocks can generate abnormal returns. Solvency is the ability of firms to cover their financial obligations. The high solvency firms are those firms with sufficient cash flows (orbalance) to cover their debt obligations while low solvency firms refer to firms that are unlikely to meet their debt obligations. The profitability of this strategy is called the solvency premium. The findings of this thesis show evidence of the solvency premium in the short-horizon but it reverts to solvency discount in the long-horizon. When the three-factor model is applied to control for risk, the solvency premium disappears. This suggests the solvency premium can be explained by risk. Further analysis, however, shows that after controlling for risk, the solvency premium exists in economic contraction and disappears during economic expansion. The solvency discount, inversely, is observed only during economic expansion. When the investors' sentiment factor is incorporated into the three-factor model, the positive and significant coefficient of investors' sentiment is observed. This suggests that investors' sentiment is also relevant in explaining solvency premium, i.e. high investors' sentiment leads to higher solvency premium. This thesis shows that three styles of investing techniques can generate superior returns (i.e. conventional contrarian trading strategy, value versus growthtrading strategies, and corporate solvency based trading strategy). However, momentum trading fails to generate any significant return. The findings benefit both individual and institutional investors to identify the stocks that are likely to generate superior returns and allocate their funds efficiently. These styles still exist until the market is more efficient relative to these styles and superior returns cannot be earned(Cao, 2011). These styles, then, disappear
An integrated framework for resource assessment and operation and maintenance cost modelling for wave energy farm
Get PDFThere is need for a framework to support the development and application of Wave Energy Converter (WEC) as an alternative source for power generation. The gaps in existing literature reveal that, the issue undermining the growth of the wave energy industry is lack of a single consistent and well documented source of information; which clearly defines the approach for preliminary assessment. The Operation and Maintenance (O&M) aspect are often not included in the feasibility studies. This is the reason for the variation surrounding the cost of electricity production using WECs. The research aims to bridge these gaps by providing an integrated framework that presents the methodology for preliminary assessment of a WEC farm project. In contrast to other studies, this research seeks to investigate the wave energy resource and contributes to providing the relevant tools to investigate the future market potential, together with opportunities for cost reduction of electricity generation using WECs. The need for understanding the offshore environment is highlighted to facilitate reliable energy yield predictions and strategies for O&M of the WEC farm. The main contribution and novelty of this thesis in comparison to past studies is the integrated framework. This is significant to support investment decisions because as well as providing a solution to the problem of resource assessment, the issues associated with variation in the O&M cost estimates are critically analysed. Results suggest that variation in the O&M cost estimates can be attributed to the decision of employing the O&M vessel for maintenance of only a single device in a WEC farm. The lack of operational experience in the wave energy sector, is identified as another problem experienced when attempting to quantify the profitability of a WEC farm project. This research addresses the problem by providing a basis and renewed support for potential wave energy industries and requirement for a generic methodology which considers the resource assessment, O&M cost and economic value of the WEC farm. Keywords: Resource Assessment, O&M, Cost, Integrated Framework.There is need for a framework to support the development and application of Wave Energy Converter (WEC) as an alternative source for power generation. The gaps in existing literature reveal that, the issue undermining the growth of the wave energy industry is lack of a single consistent and well documented source of information; which clearly defines the approach for preliminary assessment. The Operation and Maintenance (O&M) aspect are often not included in the feasibility studies. This is the reason for the variation surrounding the cost of electricity production using WECs. The research aims to bridge these gaps by providing an integrated framework that presents the methodology for preliminary assessment of a WEC farm project. In contrast to other studies, this research seeks to investigate the wave energy resource and contributes to providing the relevant tools to investigate the future market potential, together with opportunities for cost reduction of electricity generation using WECs. The need for understanding the offshore environment is highlighted to facilitate reliable energy yield predictions and strategies for O&M of the WEC farm. The main contribution and novelty of this thesis in comparison to past studies is the integrated framework. This is significant to support investment decisions because as well as providing a solution to the problem of resource assessment, the issues associated with variation in the O&M cost estimates are critically analysed. Results suggest that variation in the O&M cost estimates can be attributed to the decision of employing the O&M vessel for maintenance of only a single device in a WEC farm. The lack of operational experience in the wave energy sector, is identified as another problem experienced when attempting to quantify the profitability of a WEC farm project. This research addresses the problem by providing a basis and renewed support for potential wave energy industries and requirement for a generic methodology which considers the resource assessment, O&M cost and economic value of the WEC farm. Keywords: Resource Assessment, O&M, Cost, Integrated Framework
Imaging applications from a laser wakefield accelerator
Get PDFLaser-plasma wakefield acceleration (LWFA) is a promising technology that is attracting the attention of the scientific community. It is a new acceleration concept where electrons can be accelerated to very high energy (~150 MeV) in a very short distance (mm scale). Electrons "surf" plasma waves excited by the passage of a high power laser (~1018 Wcm-2) through plasma. Electrons in the LWFA can undergo transverse oscillation and emit synchrotron-like X-ray radiation, commonly known as betatron radiation, in a narrow cone along the laser propagation axis. The properties of both the electrons and the X-rays produced by the LWFA make them excellent candidates for a wide range of applications. In this thesis, both betatron X-ray and bremsstrahlung sources from the ALPHA-X laboratory are used to carry out both conventional imaging and X-ray phase-contrast imaging experiments to explore the feasibility of real-world applications. The characterisation of the betatron X-ray radiation produced by the LWFA in the ALPHA-X laboratory is presented. In the last Chapter, a brief discussion of the potential of LWFA technology for clinical applications is presented.Laser-plasma wakefield acceleration (LWFA) is a promising technology that is attracting the attention of the scientific community. It is a new acceleration concept where electrons can be accelerated to very high energy (~150 MeV) in a very short distance (mm scale). Electrons "surf" plasma waves excited by the passage of a high power laser (~1018 Wcm-2) through plasma. Electrons in the LWFA can undergo transverse oscillation and emit synchrotron-like X-ray radiation, commonly known as betatron radiation, in a narrow cone along the laser propagation axis. The properties of both the electrons and the X-rays produced by the LWFA make them excellent candidates for a wide range of applications. In this thesis, both betatron X-ray and bremsstrahlung sources from the ALPHA-X laboratory are used to carry out both conventional imaging and X-ray phase-contrast imaging experiments to explore the feasibility of real-world applications. The characterisation of the betatron X-ray radiation produced by the LWFA in the ALPHA-X laboratory is presented. In the last Chapter, a brief discussion of the potential of LWFA technology for clinical applications is presented
Function and localization of Leishmania mexicana MAP kinase 2
No full textLeishmaniasis is a life threatening tropical disease caused by Leishmania parasites that are transmitted by blood feeding sand flies. This disease affects approximately 12 million people worldwide, leaving another 350 million more at risk in endemic areas. Roughly two million new cases are reported annually with nearly 60,000 mortality rate. Treatment improvements have been slow in the past century, resulting in ineffective single treatment approach patient care with toxic side effects to current drugs at an expensive cost. These flows accents the ugency for a safer, a 'Combination Regime' treatment approach at an affordable rate.;LmxMPK2, a mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana, is expressed in the amastigote and promastigote life stages of Leishmania parasites. Previous research (PhD, Laura Munro 2013) suggested that LmxMPK2 is involved in the organisation of microtubules, influencing cell shape and cytokinesis. A homozygous gene knock out mutant (null mutant) for LmxMPK2 in the promastigote stage was generated with deletions that caused alterations in cell proliferation and morphology, resulting to variations in the cell shape with spiked posterior ends, as well as division channel ingression from the posterior end.;MAP kinases are known to be key regulatory elements in cell cycle progression, proliferation, differentiation, as well as in stress responses in Leishmania cells (Wiese et al., 2003). Therefore, understanding the function of MAP kinases in Leishmania is essential and therefore relevant to the pursuit of new treatment approaches for leishmaniasis. In this study two constructs were generated that allowed the expression of Green Fluorescence Protein-tagged MPK2 (MPK2GFP) in the ribosomal DNA locus and Red Fluorescence Protein-tagged Deflagellation inducible protein 13 (RFPDIP13) from a plasmid.;Live cell fluorescence microscopy of cloned cells confirmed the expression of MPK2GFP and RFPDIP13 in both the promastigote and amastigote life stages in Leishmania cells. GFP-tagged LmxMPK2 showed localisation primarily at the poles, with occasional localisation at the centre of the cells. L. mexicana wild type; two LmxMPK2 null mutant clones; two LmxMPK2 add back clones; and four LmxMPK2 add back clones co-expressing RFPDIP13, were differentiated from the promastigote to the amastigote life stage for further analysis.;Although all cells were differentiable into the amastigote form, only cells expressing LmxMPK2 showed proliferation after differentiation. This observation suggests that the null mutant Leishmania cells (knock out; no LmxMPK2) are unable to survive under amastigote conditions. Hence, targeting LmxMPK2 with a specific inhibitor in the amastigote stage could significantly impact the course of treatment for leishmaniasis.Leishmaniasis is a life threatening tropical disease caused by Leishmania parasites that are transmitted by blood feeding sand flies. This disease affects approximately 12 million people worldwide, leaving another 350 million more at risk in endemic areas. Roughly two million new cases are reported annually with nearly 60,000 mortality rate. Treatment improvements have been slow in the past century, resulting in ineffective single treatment approach patient care with toxic side effects to current drugs at an expensive cost. These flows accents the ugency for a safer, a 'Combination Regime' treatment approach at an affordable rate.;LmxMPK2, a mitogen-activated protein (MAP) kinase homologue of Leishmania mexicana, is expressed in the amastigote and promastigote life stages of Leishmania parasites. Previous research (PhD, Laura Munro 2013) suggested that LmxMPK2 is involved in the organisation of microtubules, influencing cell shape and cytokinesis. A homozygous gene knock out mutant (null mutant) for LmxMPK2 in the promastigote stage was generated with deletions that caused alterations in cell proliferation and morphology, resulting to variations in the cell shape with spiked posterior ends, as well as division channel ingression from the posterior end.;MAP kinases are known to be key regulatory elements in cell cycle progression, proliferation, differentiation, as well as in stress responses in Leishmania cells (Wiese et al., 2003). Therefore, understanding the function of MAP kinases in Leishmania is essential and therefore relevant to the pursuit of new treatment approaches for leishmaniasis. In this study two constructs were generated that allowed the expression of Green Fluorescence Protein-tagged MPK2 (MPK2GFP) in the ribosomal DNA locus and Red Fluorescence Protein-tagged Deflagellation inducible protein 13 (RFPDIP13) from a plasmid.;Live cell fluorescence microscopy of cloned cells confirmed the expression of MPK2GFP and RFPDIP13 in both the promastigote and amastigote life stages in Leishmania cells. GFP-tagged LmxMPK2 showed localisation primarily at the poles, with occasional localisation at the centre of the cells. L. mexicana wild type; two LmxMPK2 null mutant clones; two LmxMPK2 add back clones; and four LmxMPK2 add back clones co-expressing RFPDIP13, were differentiated from the promastigote to the amastigote life stage for further analysis.;Although all cells were differentiable into the amastigote form, only cells expressing LmxMPK2 showed proliferation after differentiation. This observation suggests that the null mutant Leishmania cells (knock out; no LmxMPK2) are unable to survive under amastigote conditions. Hence, targeting LmxMPK2 with a specific inhibitor in the amastigote stage could significantly impact the course of treatment for leishmaniasis
Rapid pre-symptomatic diagnosis of sepsis by vibrational spectroscopy
Get PDFSepsis is a dysregulated host response to an infection that causes life-threatening organ dysfunction. Each year, over 30 million cases and 5 million deaths are estimated worldwide. Diagnosis of sepsis is based on non-specific clinical signs and time consuming positive identification of the causative pathogen(s). Rapid presymptomatic detection of sepsis would enable the early administration of therapeutics, maximising their effects, reducing mortality and healthcare costs. Vibrational spectroscopy can provide a "molecular fingerprint" of biological materials and presents many advantageous aspects. Indeed, this technique is label-free, nondestructive, non-contact, rapid, cost-effective, simple to operate, and requires only simple sample preparation. The objective of this study was to develop and evaluate the potential of vibrational spectroscopy applied on human serum with the aim to improve diagnosis of patients with sepsis. Challenges of serum spectroscopy inherent to the sample nature and to the technique have been assessed. Different infrared and Raman spectroscopy modalities as well as different serum sample preparations have been compared to determine the most suitable methodology approach with an overall clinical application purpose. Then, some aspects of the pre-analytical phase have been addressed in order to standardise protocols in sample handling and preparation for spectral acquisitions to ensure quality and reproducibility of spectral data collected.;Finally, based upon the developed methodology, patient serum samples (n=380) collected before surgery, up to 3 days before sepsis diagnosis, and on the day of sepsis diagnosis have been analysed. Control serum samples (n=353) from age/ sex/ procedure-matched patients who did not go on to develop sepsis have been also analysed over similar timeframes post-surgery as well as samples (n=190) from patients with systemic inflammatory response syndrome. Spectral data acquired have been interrogated by chemometric methods to discriminate spectral zones reflecting differences in molecular composition.Sepsis is a dysregulated host response to an infection that causes life-threatening organ dysfunction. Each year, over 30 million cases and 5 million deaths are estimated worldwide. Diagnosis of sepsis is based on non-specific clinical signs and time consuming positive identification of the causative pathogen(s). Rapid presymptomatic detection of sepsis would enable the early administration of therapeutics, maximising their effects, reducing mortality and healthcare costs. Vibrational spectroscopy can provide a "molecular fingerprint" of biological materials and presents many advantageous aspects. Indeed, this technique is label-free, nondestructive, non-contact, rapid, cost-effective, simple to operate, and requires only simple sample preparation. The objective of this study was to develop and evaluate the potential of vibrational spectroscopy applied on human serum with the aim to improve diagnosis of patients with sepsis. Challenges of serum spectroscopy inherent to the sample nature and to the technique have been assessed. Different infrared and Raman spectroscopy modalities as well as different serum sample preparations have been compared to determine the most suitable methodology approach with an overall clinical application purpose. Then, some aspects of the pre-analytical phase have been addressed in order to standardise protocols in sample handling and preparation for spectral acquisitions to ensure quality and reproducibility of spectral data collected.;Finally, based upon the developed methodology, patient serum samples (n=380) collected before surgery, up to 3 days before sepsis diagnosis, and on the day of sepsis diagnosis have been analysed. Control serum samples (n=353) from age/ sex/ procedure-matched patients who did not go on to develop sepsis have been also analysed over similar timeframes post-surgery as well as samples (n=190) from patients with systemic inflammatory response syndrome. Spectral data acquired have been interrogated by chemometric methods to discriminate spectral zones reflecting differences in molecular composition
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