Beta-amyloid (Aâ) remains to be the focus of research interest of the pathogenesis of Alzheimers disease (AD). Aâ is subject to oligomerization and its polymers are cytotoxic. Advanced aggregation leads to formation of senile plaques. Depositions of Aâ surrounding the cerebral vasculature, i.e. cerebral amyloid angiopathy (CAA), occur in most AD patients. The occurrence of Aâ aggregation in AD brains is not due to over-expression of amyloid precursor protein in most cases of AD. Factors influencing Aâ polymerization are yet to be established.<p> Aldehydes are highly reactive. They can cause protein crosslinkage. It is interesting to study whether endogenous aldehydes may be involved in Aâ polymerization process. In order to investigate the potential interaction of endogenous aldehydes with Aâ and their effects on its aggregation, various techniques including thioflavin T fluometry, dynamic light scattering, circular dichroism and atomic force microscopy were employed to assess Aâ aggregation at different stages. Formaldehyde, methylglyoxal, malondialdehyde and 4-hydroxyl-nonenal were found to enhance Aâ â-sheets formation, oligomerization and fibrillogenesis in vitro. The sizes of the oligomers are increased after interaction with the aldehydes. Lysine residues of Aâ were identified to be the primary site of interaction with aldehydes by forming Schiff bases, which may subsequently lead to intra- and inter-molecular crosslinkage. Aldehydes can also crosslink Aâ with other proteins such as apolipoprotein E and á2-macroglobulin (á2M), to form large complexes. Results suggest that aldehydes substantially increase the rate of Aâ oligomerization at each stage of fibrillogenesis.<p> The native and formaldehyde-modified Aâ oligomers were isolated by size exclusion chromatography and their cytotoxic effects towards SH-SY5Y neuroblastoma cells were assessed using MTT, LDH and caspase-3 activity assays. The aldehyde-modified oligomers are slightly but significantly more cytotoxic compared to the native oligomers. Since aldehydes significantly increase the production of Aâ oligomers, an increase in aldehydes would enhance the total cytotoxicity, suggesting that aldehydes may potentially exacerbate neurovascular damage and neurodegeneration caused by Aâ.<p> Low-density lipoprotein receptor related protein-1 (LRP-1) plays a crucial role in Aâ clearance via the cerebral vasculature. Semicarbazide-sensitive amine oxidase (SSAO) and LRP-1 are both richly expressed on the vascular smooth muscle cells (VSMCs). We demonstrated that SSAO-mediated deamination affects LRP-1 function using isolated VSMCs. Formaldehyde at low concentrations decreases LRP-1-mediated uptake of á2M, a substrate of LRP-1 and a carrier for Aâ. Methylamine, an SSAO substrate that is converted to formaldehyde, also inactivates LRP-1 function, but not in the presence of an SSAO inhibitor. Increased SSAO-mediated deamination can potentially impair Aâ clearance via LRP-1.<p> In conclusion, aldehydes derived from oxidative stress and SSAO-mediated deamination induce Aâ aggregation, enhance Aâ cytotoxicity and impair Aâ clearance. The exclusive localization of SSAO on the cerebral vasculature may be responsible for the perivascular deposition of Aâ, i.e. CAA, which is associated both with vascular dementia and with AD. Vascular surface SSAO may be a novel pharmacological target for the treatment of AD.

The rate of economic growth varies extensively between different countries. The underlying reasons to the differences are dissimilarities in productivity and efficiency, which in turn seem to be affected by factors such as the institutional setup, the rate of economic freedom, the level of human and social capital, corruption and interpersonal trust.This thesis investigates the relationship between economic growth and the level of democracy in developing countries, as a well-functioning democracy to a large extent corresponds to an inclusive institutional setup. The empirical investigation is conducted with a regression analysis. Using secondary data from acknowledged organizations and institutes, possible factors that may affect average GDP per capita growth are examined. The estimations included in the regression are democracy, foreign direct investment, education expectancy, initial GDP per capita, population growth rate, life expectancy, corruption, Rule of Law and Internet users. The empirical result shows that democracy has no significant effect on growth, but suggests that the effect might be indirect since factors such as good maintenance of Rule of Law, low level of corruption, high interpersonal trust, a high level of economic freedom and enhanced property rights are empirically proven to correspond to well functioning institutions. This result is in accordance with previous research and seems to support the idea that a good institutional setup is important for economic growth.

<p>This dissertation presents two essays on endogenous growth and renewable resources.</p><p>The first essay explores the role of renewable resources in a tractable</p><p>model of endogenous growth driven by horizontal and vertical innovation in the closed economy.</p><p>The model is tractable in that it yields a complete, analytical characterization</p><p>of the path of utility and the associated welfare level. This property</p><p>is exploited to compare two cases of renewable resource management:</p><p>open access and full property rights. The first case involves a common</p><p>property problem in which agents ignore the long-term resource viability;</p><p>the second fully internalizes the dynamics of the resource stock.</p><p>Analysis shows that if the natural regeneration rate of the renewable</p><p>resource is too low, the tragedy of the commons occurs. If, instead,</p><p>the natural regeneration rate is sufficiently high, the steady-state</p><p>growth rate of the economy is identical across the two management</p><p>regimes. The reason is because there is no scale effect; that is,</p><p>the steady-state growth rate of the economy does not depend on the</p><p>labor or the resource endowment. However, the development path on</p><p>which the economy transits from the developing stage (no R\&D activity)</p><p>to the developed stage (positive R\&D activity) depends on the resource</p><p>management regime. In particular, a developing economy under full</p><p>property rights will cross its development threshold prior to one</p><p>under open access. This threshold depends on the size of the manufacturing</p><p>firms. When it becomes sufficiently large as a result of the decline</p><p>in the number of firms over time, there will be an incentive for the</p><p>remaining firms to conduct R\&D. Given the same number of manufacturing</p><p>firms, the firm size is larger under full property rights than under</p><p>open access due to higher nominal expenditure per capita. Therefore,</p><p>the development threshold will be reached sooner under full property</p><p>rights. In other words, the economy will start engaging in R\&D activities</p><p>sooner and more quickly accumulate knowledge, which is the source</p><p>of long-run growth. Moreover, switching from full property rights</p><p>to open access is welfare reducing due to two effects. The first is</p><p>through the price of the harvest good. Although the economy initially</p><p>enjoys a lower price of harvest good, the price gradually increases</p><p>as the resource becomes scarcer. Secondly, the competitive household</p><p>instantaneously loses the resource income and thus spends less on</p><p>manufacturing goods. This decreases the incentive for manufacturing</p><p>firms to conduct R\&D and results in a temporary deceleration of the</p><p>growth rate of TFP relative to the baseline case of full property</p><p>rights. The economy therefore experiences a cumulative loss of TFP</p><p>relative to the baseline, which is the novel feature of our model</p><p>of endogenous innovation. This mechanism has interesting and wide-ranging</p><p>implications for the role of resources in development and growth</p><p>The second essay extends the model of endogenous growth and renewable </p><p>resources into the open economy framework. The paper examines the effect of trade liberalization on resource-rich</p><p>countries, based on a two-country model in which the difference in</p><p>endowment of a renewable resource leads to asymmetric trade. In this</p><p>model, the resource-rich economy trades its harvest good and final</p><p>good for the final good from the resource-poor economy. Furthermore,</p><p>the renewable resource is considered to be under open access, where</p><p>there is no clear ownership over the resource, leading to overexploitation.</p><p>Long-term productivity, in this case, stems from endogenously-determined</p><p>knowledge accumulation. Under these circumstances, analysis shows</p><p>that the resource-rich country will lose from trade due to two effects.</p><p>The first effect is the instantaneous loss of income. Higher demand</p><p>for the harvest good, from the combined domestic and international</p><p>demand, diverts labor away from the production of technological goods</p><p>to the harvest sector, where rent is zero. The second effect is a</p><p>scarcity effect, which becomes more severe when trade results in a</p><p>greater demand for the harvest good. Overexploitation of the renewable</p><p>resource today leads to falling resource stock in the future, which</p><p>is then reflected in the higher price of harvest good, other things</p><p>being constant. Since the harvest good is an essential input to produce</p><p>the final good, given the same amount of the other inputs, the amount</p><p>of final good produced will also fall in the long run.</p> / Dissertation

<p>This dissertation aims to introduce a new sequential Monte Carlo (SMC) based estimation framework for structural models used in macroeconomics and industrial organization. Current Markov chain Monte Carlo (MCMC) estimation methods for structural models suffer from slow Markov chain convergence, which means parameter and state spaces of interest might not be properly explored unless huge numbers of samples are simulated. This could lead to insurmountable computational burdens for the estimation of those structural models that are expensive to solve. In contrast, SMC methods rely on the principle of sequential importance sampling to jointly evolve simulated particles, thus bypassing the dependence on Markov chain convergence altogether. This dissertation will explore the feasibility and the potential benefits to estimating structural models using SMC based methods.</p><p> Chapter 1 casts the structural estimation problem in the form of inference of hidden Markov models and demonstrates with a simple growth model.</p><p> Chapter 2 presents the key ingredients, both conceptual and theoretical, to successful SMC parameter estimation strategies in the context of structural economic models.</p><p> Chapter 3, based on Chen, Petralia and Lopes (2010), develops SMC estimation methods for dynamic stochastic general equilibrium (DSGE) models. SMC algorithms allow a simultaneous filtering of time-varying state vectors and estimation of fixed parameters. We first establish empirical feasibility of the full SMC approach by comparing estimation results from both MCMC batch estimation and SMC on-line estimation on a simple neoclassical growth model. We then estimate a large scale DSGE model for the Euro area developed in Smets and Wouters (2003) with a full SMC approach, and revisit the on-going debate between the merits of reduced form and structural models in the macroeconomics context by performing sequential model assessment between the DSGE model and various VAR/BVAR models.</p><p> Chapter 4 proposes an SMC estimation procedure and show that it readily applies to the estimation of dynamic discrete games with serially correlated endogenous state variables. I apply this estimation procedure to a dynamic oligopolistic game of entry using data from the generic pharmaceutical industry and demonstrate that the proposed SMC method can potentially better explore the parameter posterior space while being more computationally efficient than MCMC estimation. In addition, I show how the unobserved endogenous cost paths could be recovered using particle smoothing, both with and without parameter uncertainty. Parameter estimates obtained using this SMC based method largely concur with earlier findings that spillover effect from market entry is significant and plays an important role in the generic drug industry, but that it might not be as high as previously thought when full model uncertainty is taken into account during estimation.</p> / Dissertation

This thesis aims to propose a policy-relevant science, technology and innovation indicator for developing countries. I firstly develop a model to examine the determination of innovativeness for a sample of 38 developing countries, based on endogenous growth theory and innovation systems literature. From econometric estimation, I find that R&D inputs, technology imports, and international connectedness are influential determinants of innovativeness in these countries. From this finding, I develop the Predicted Innovativeness Index for Developing Countries (INNÔDEX), a composite indicator that ranks countries according to their innovative capabilities.

This paper adopts an modle with endogenous variable to investigates policy inertia hypothesis or unobserved variable hypothesis in Taiwan¡¦s interest-rate rule 1981- 2010. Empirical result suggests that both policy inertia and omitted variable hypothesis are important in monetary policy in Taiwan,which is consistent with that of Gerlach- Kristen (2004).

The design and development of a versatile time resolved fluorescence spectroscopy (TRFS) system capable of near real time data acquisition and processing for potential clinical diagnostic applications is reported. The TRFS apparatus is portable, versatile and compatible with the clinical environment. The main excitation source is a UV nitrogen laser with a nanosecond pulse width and the detection part consists of a dual grating spectrograph coupled with an MCP-PMT. The nitrogen laser also has a dye module attached to it, which enables broadband excitation of the sample. This setup allows rapid acquisition (250 ms for fluorescence decay at a wavelength) of time resolved fluorescence data with a high spectral (as low as 0.5 nm) and temporal (as low as 25 picoseconds) resolution. Alternatively, a state diode pumped pulsed laser can be used for excitation to improve data collection speed. The TRFS system is capable of measuring a broad range of fluorescence emission spectra (visible to near infra-red) and resolving a broad range of lifetimes (ranging from a few hundred picoseconds to several microseconds). The optical setup of the system is flexible permitting the connection of different light sources as well as optical fiber based probes for light delivery/collection depending on the need of the application. This permits the use of the TRFS apparatus in in vitro, ex vivo and in vivo applications. The system is fully automated for real-time data acquisition and processing, facilitating near-real time clinical diagnostic applications.

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Beginning with the paper of Zhang (2000), we develop a pecuniary transactions cost (TC) approach to build up a monetary endogenous growth model and examine the principal relationships and results concerning nominal interest rate targeting and growth. Meanwhile, according to Hahn (1991) and Eriksson (1995) pointed out there has been a trend decline in labor supply, we introduce the labor-leisure choice of Turnovsky (2000) to amend the utility function and the production function. In the comparison of two macro-models, we can conclude: 1. Under the inelastic labor supply endogenous growth model, if the central bank raises the nominal interest rate targeting will damage to the growth rate. 2. Under the elastic labor supply endogenous growth model, if the central bank raise the nominal interest rate targeting will induce ambiguous effect of the growth rate depending on the labor-leisure choice reaction of nominal interest rate, the bigger reaction may get the higher growth rate.

This dissertation performs economic analysis of search advertising from a comprehensive picture of the competition facing advertisers---by incorporating the price competition to endogenously investigate advertisers' bidding incentive, and taking into account consumers' online search and the unique information structure associated with the search advertising format. It consists of three essays based on game-theoretic modeling. The first essay studies the oligopolistic price competition among advertisers placed in different advertising positions, considering distinctive features of consumers’ online search behaviors. We find an interesting local-competition pattern in which direct price competition occurs only between advertisers adjacent to each other. The second essay integrates the price competition into the bidding competition and investigates the endogenous bidding incentives of advertisers with different competitive strengths. Surprisingly, we find that an advertising position with a better exposure may not always be profitable for the advertisers with competitive advantage, even if it is cost free. We also show that the bidding outcome might not align with the relative competitive strength. The third essay further considers the effects of organic listing as a competing information source on the sponsored bidding competition and the outcome performances in search advertising. It provides answers to questions such as whether and why advertisers with sufficient exposure from the organic list may still be willing to bid for top sponsored positions, and how the existence of organic listing affects search engine’s revenue, consumer surplus, and social welfare. / text