In recent years, increasing attention has turned toward the effect of health information or health knowledge on nutrient intake. In determining the effect of health information on nutrient demand, researchers face the estimation problem of dealing with the endogeneity of health information knowledge. The standard approach for dealing with this problem is an instrumental variables (IV) procedure. Unfortunately, recent research has demonstrated that the IV procedure may not be reliable in the types of data sets that contain health information and nutrient intakes because the instruments are not sufficiently correlated with the endogenous variables (i.e., instruments are weak). This thesis compares the reliability of the IV procedure (and the Hausman test) with a relatively new procedure, directed graphs, given weak instruments. The goal is to determine if the method of directed graphs performs better in identifying an endogenous variable and also relevant instruments. The performance of the Hausman test and directed graphs are first assessed through conducting a Monte-Carlo sampling experiment containing weak instruments. Because the structure of the model is known in the Monte-Carlo experiment, these results are used as a guideline to determine which procedure would be more reliable in a real world setting. The procedures are then applied to a real-world cross-sectional dataset on nutrient intake. This thesis provides empirical evidence that neither the IV estimator (and Hausman test) or the directed graphs are reliable when instruments are weak, as in a cross-sectional dataset.

Alzheimer’s disease (AD) is a progressive, degenerative neurological disorder for which there is no cure. The causative agent is ?-amyloid (A?) which becomes neurotoxic upon conformational change from ?-helix to ?-sheet. In silico methods have been used to indentify endogenous small molecules of the brain that are capable of binding to A? to inhibit conformational changes; this is a novel approach to the disease. Through the use of computational methods, several small molecules that are endogenous to the brain, such as phosphoserine, have been identified as being capable of binding to the monomeric forms of A?; in vitro studies support their role as anti-aggregants. One of the small molecules identified through these in silico methods, 3-hydroxyanthranilic acid (3HAA) has been developed through the use of Quantitative Structure-Activity Relationship (QSAR) studies to design more potent analogues. These in silico studies have also examined the capacity of synthetic compounds (structurally similar to endogenous molecules) to bind to both A? and other proteins affiliated with AD. Results indicate the potential for a single molecule to bind “promiscuously” to multiple proteins bearing a common BBXB (where B is a basic amino acid) motif affiliated with AD. This will allow for the development of molecules to target AD in a multifaceted approach. Furthermore, these small molecules can be selected through the use of “physinformatics” to bind with equal efficacy to the HHQK and LVFF regions (which play a role in the misfolding process) of A?; this will prevent conformational changes of the protein. A novel diagnostic imaging agent for AD has also been developed through computational methods; solapsone (formerly used to treat leprosy) has been identified as being structurally similar to species that bind to A? to initiate conformational changes. Results show that solapsone can chelate gadolinium, used in MRI, and bind to the soluble forms of A?, allowing for imaging of the toxic species in the human brain, and thus a definitive diagnosis of AD (which is not currently possible with living patients). Computational methods have proved useful in developing a new approach to treating AD, and designing a novel imaging agent.

This dissertation adds to the literature on international openness and economic growth by studying and quantifying the effects of openness to trade and multinational production using a model of endogenous innovation with firm heterogeneity. The first chapter discusses the contribution of this dissertation to the theoretical and empirical literature on international openness. The second chapter studies and quantifies the long-run effects of openness to trade and multinational production in the context of advanced economies using a model of endogenous innovation with firm heterogeneity. Counterfactual experiments conducted using a calibrated version of a theoretical model find that the US would experience a significant welfare cost in consumption terms by restricting openness to both trade and horizontal multinational production with other OECD countries, with the growth effect accounting for a substantial part of the cost. Chapter Three extends the theoretical model presented in Chapter Two to include features specific to the North-South context. I show that allowing for the possibility that the South may switch from being an imitator to becoming an innovator is essential for examining the long-run growth effect of stronger intellectual property rights. In particular, the North and the South both prefer stronger intellectual property rights because this will achieve the fastest long-run economic growth. If the South is an imitator country, the North needs to maintain its absolute advantage in technology creation by maintaining a sufficiently large pool of uncopied ideas. Otherwise both countries will fall into a slow-growth equilibrium in the long run. In Chapter Four, I account for transitional dynamics and study the gains from openness and stronger intellectual property rights that arise in the North-South context. Counterfactual experiments based on a calibrated version of the model presented in Chapter Three find that the transitional welfare gains from further trade openness between China and the OECD countries can be significant. In contrast to the existing growth literature, a deterrence of imitation has limited welfare effects when the South can switch from being an imitator to becoming an innovator country. This points to a source of potential bias in the welfare estimates provided by the existing literature. / Thesis (Ph.D, Economics) -- Queen's University, 2012-05-18 10:18:34.338

This paper investigates the growth factors of EU regions in the 1990s. We test the hypothesis that regional growth is determined by endogenous growth factors, trade and technological catching-up in a growth accounting framework. Our estimations suggest that growth of EU regions is positively related to the accumulation of physical and human capital. Innovation activity as well as international technology transfer are important for growth. The latter is facilitated if a region is well endowed with human capital. Further, we observe that technological catching-up is promoted by intensive foreign trade, a result which underlines the importance of trade openness for EU regions. (authors' abstract) / Series: EI Working Papers / Europainstitut

Morphine is the most widely prescribed opiate for alleviation of persistent pain; however, it is becoming increasingly clear that morphine is less potent in women compared to men. Morphine primarily binds mu opioid receptors, which are densely localized in the midbrain periaqueductal gray (PAG). Anatomical and physiological studies conducted in the 1960s identified the PAG, and its projections to the rostral ventromedial medulla (RVM) and spinal cord dorsal horn, as an essential neural circuit mediating opioid-based analgesia. Remarkably, the majority of studies since then were conducted in males with the implicit assumption that this circuit was the same in females; this is not the case. It is now well established that morphine produces greater analgesia in males compared to females in a wide range of vertebrates, however, the mechanism(s) driving this sex difference is not clear. Our recent studies indicate that two factors appear to be contributing to the sexually dimorphic effects of morphine. First, there are sex differences in the anatomy and physiology of the descending inhibitory pathway on which morphine acts to produce analgesia. Specifically, the projections from the PAG to the RVM are sexually dimorphic and activated to a greater degree by both inflammatory pain and systemic morphine in males. In the absence of pain, the PAG-RVM circuit is activated to a greater degree in males compared to females, while this activation steadily declines during the development of tolerance in males only. We also have evidence of a sexually dimorphic expression of mu opioid receptor within the PAG that appears to contribute to sex differences in morphine potency. Microinjection of morphine directly into the PAG produces significantly greater analgesia in males, indicating that the PAG is sufficient for eliciting this sexually dimorphic behavior. Furthermore, mu opioid receptor-expressing PAG neurons are necessary for eliciting a sexually dimorphic response to morphine as lesioning mu opioid receptor-expressing neurons attenuates analgesia in males only. Together, these data indicate that the PAG-RVM pathway and mu opioid receptor expression in the PAG is sexually dimorphic and provides a primary mechanism for sex differences in morphine potency.

This paper studies the dynamics of an asset pricing model based on simple deterministic agents. Traders are heterogeneous with respect to their time horizon, prediction function and trade interval. Concerning the trade interval we distinguish between intraday traders and end-of-day traders. Intraday traders update their portfolio every period, whereas end-of-day traders adjust their positions only at the closing price of each trading day. The parameter values of the model were partially determined by an adapted Markov chain Monte Carlo sampling method. We analyse the properties of the time series and find that they exhibit low autocorrelation of the returns, volatility clustering and fat tails. Particularly heterogeneous trade intervals seem to be an important factor for generating time series showing "stylized facts". (author's abstract) / Series: Working Papers SFB "Adaptive Information Systems and Modelling in Economics and Management Science"

Performance and exercise capacity in prolonged continuous exercise has been shown to be enhanced by the ingestion of dilute (-6%) carbohydrate-electrolyte (CHO-E) solutions during exercise. There is a wealth of literature on the effects of CHO-E solutions on prolonged, continuous exercise however this is not the case for highintensity intermittent exercise. One reason for this is the difficulty of replicating the demands of multiple-sprint sports within the laboratory. The development of the Loughborough Intermittent Shuttle Running Test (LIST), a protocol that simulates the physiological demand of multiple-sprint sports, has allowed for further study in this area. Sports drinks contain a variety of different types of carbohydrate, including synthetic polymers of maltodextrins. The rationale for these is two-fold; firstly there is some evidence to suggest that these glucose polymers of low osmolality may empty faster than isoenergetic glucose solutions especially at dilute (-6%) concentrations. Secondly CHO-E solutions formulated from maltodextrins with low dextrose equivalents are less acidogenic and have lower cariogenic potential than simple glucose solutions, thus making them preferable for tooth health. Therefore the purpose of this thesis was to examine the effects of a 6.4% hypotonic synthetic polymer maltodextrin CHO-E solution on muscle metabolism and physiological performance during prolonged high-intensity intermittent running (LIST). This thesis contains four experimental studies. From the results of study 1 it was concluded that the ingestion of a 6.4% hypotonic CHO-E solution provided no ergogenic benefit to running capacity during the LIST despite blood and hormonal data suggesting that the solution was effective at delivering glucose. As isotonic CHO-E solutions have shown to have ergogenic properties during LIST running the purpose of study 2 was to compare isoenergetic hypotonic and isotonic CHO-E solutions during LIST running. The results from this study suggested that performance, as measured by exercise capacity and sprint speed, was not affected by either treatment. In study 3 the protocol was modified to extend the exercise duration so that a greater demand was placed on the subjects' glycogen reserves. The results from this study further confirmed that exercise capacity in LIST running was not influenced by CHO provision during exercise however the habitual CHO intake of the subjects may have masked any ergogenic properties of the CHO-E solution and led to increased performance in the control trials. In the final study the subjects' pre-trial exercise and dietary CHO intake was manipulated to increase endogenous glycogen concentrations. The results showed that in these subjects the ingestion of a 6.4% hypotonic CHO-E solution increased exercise capacity during the LIST by 21%. Muscle biopsy analyses revealed a lower net muscle glycogen utilisation in the CHO trial post-90 min (p=0.07). There is evidence in the literature to suggest that there is an ergogenic effect of CHO ingestion during the LIST. However the results presented in this thesis suggest that when endogenous glycogen stores are moderate the ingestion of a CHO-E solution may suppress lipid oxidation without a concomitant increase in CHO oxidation and thus LIST capacity is not enhanced. In contrast, when endogenous glycogen concentrations are elevated through dietary manipulation there is an ergogenic benefit from the ingestion of hypotonic CHO-E solutions during LIST exercise.

The current approach to African development is driven by Euro-Western material/physical approaches that fail to acknowledge the integral link between culture and development. For African development to truly speak to the realities and needs of African peoples, a reconceptualization of development is necessary, one which examines how Indigenous African knowledges can inform development. Using an anti-colonial, critical development and Indigenous discursive frameworks, this thesis examines how Akan, Gonja and Bogon proverbs, as Indigenous African knowledges, provide theoretical and practical knowledges for reconceptualising localized approaches to African development. Through interviews with local development practitioners and local Chiefs and the analysis of collected proverbs, the thesis reveals that proverbs, as linguistic, cultural and spiritual knowledges are deeply embedded in Ghanaian life and may function as excellent culturally relevant tools for a localized approach to African development.

The current approach to African development is driven by Euro-Western material/physical approaches that fail to acknowledge the integral link between culture and development. For African development to truly speak to the realities and needs of African peoples, a reconceptualization of development is necessary, one which examines how Indigenous African knowledges can inform development. Using an anti-colonial, critical development and Indigenous discursive frameworks, this thesis examines how Akan, Gonja and Bogon proverbs, as Indigenous African knowledges, provide theoretical and practical knowledges for reconceptualising localized approaches to African development. Through interviews with local development practitioners and local Chiefs and the analysis of collected proverbs, the thesis reveals that proverbs, as linguistic, cultural and spiritual knowledges are deeply embedded in Ghanaian life and may function as excellent culturally relevant tools for a localized approach to African development.

In endogenous growth models, in contrast to the neoclassical growth models, government expenditure and taxation have an effect on the long run growth rate. In this thesis I examine whether the empirical evidence support the predictions of endogenous growth models or the neoclassical growth models in relation to fiscal policy. For this purpose I use panel data for fifteen European Union (EU) member and thirty-three developing countries between the years 1970 and 1999. I specifically test the following two propositions. The first proposition states that distortionary taxation decreases growth while non-distortionary taxation does not. The second, states that productive government expenditure increases growth while non-productive expenditure does not. The empirical results are quite different between European Union countries and developing countries. The results do not support endogenous growth especially for developing countries.