本文利用一個與Barro(1990)及Koichi et al.(1993)相類似的模型，來探討一個具有私人資本及生產性公共財的內生性成長模型，其最大的差異是利用對偶性的原理，將模型簡化，以分析複雜的兩財模型。本文的重點有三： 　　(1)探討均衡解的存在，唯一及穩定性。 　　(2)描繪出當體系受干擾時，內生變數收歛的方向。 　　(3)探討稅率的比較靜態分析。

The first essay constitutes a theory which lends truth to the Kuznets hypothesis. The attention is centered on the role of financial markets in defining the process of knowledge accumulation, and ultimately the distribution of income earning capabilities in a population of ex ante heterogeneous individuals. The provision of credit is hindered by one-sided lack of commitment embedded in the area of educational investment. Adaptation in the legislative system to accommodate a punishment scheme conditional on default is the critical requirement for the economy to be carried on a dynamic growth path, albeit one of higher and worsening inequality. Owing to the accumulation of human capital and the associated externality on future generations’ knowledge productivity, the economy ultimately makes its transition to a state of lower income differentials. The second essay is an enquiry on the role of monetary policy in determining the growth dynamics of a small open economy. We postulate that the possibility of intermediated credit does not exist, the intention of the assumption being to uncover the role of inflation as tax on private spending. The analysis brings a valid argument of the superneutrality of money. Inflation when operating as consumption tax has no impact on the growth rate of output. This is established irrespective of the labor supply be held fixed, or incorporated as endogenous decision. When imitating the role of capital taxation, inflationary policy has a negative effect on capital accumulation in a framework of fixed labor supply. However, the validity of the superneutrality result is once again reestablished in an environment accommodating the endogeneity of labor supply. The third essay is a theoretical investigation of the long-run effects of tax and expenditure policies in an open economy framework. The aim is to establish an analytic basis for the factual evidence associated with the non-monotonic response of the current account to fiscal shocks. To this endeavor we sought two sources of time non-separability in the preference structure, habit-forming consumption in consumer durable goods. Optimal private choices induce non-monotonic dynamics on consumption behavior that are exactly consistent with the evidence on the current account.

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.

The neonatal period represents a critical window of increased neurodevelopmental plasticity in the immature nervous system. Unlike other sensory modalities, which require appropriate stimulation for proper development, maturation of nociceptive circuitry in neonates typically occurs in the absence of noxious stimulation. Premature infants, however, are routinely exposed to multiple invasive medical procedures during neonatal intensive care treatment, which are largely performed in the absence of anesthetics or analgesics. To date, it is largely unknown how exposure to early noxious insult during this time of increased plasticity alters the development of the CNS and influences future nociceptive responses. As previous studies examining the impact of neonatal inflammatory insult on adult nociceptive responses have been conducted primarily in males, the potential adverse effects in females are unknown. Furthermore, the biological mechanisms underlying neonatal insult-induced deficits in nociceptive processing have yet to be elucidated. Therefore, this dissertation addressed the following questions: (1) Does neonatal inflammatory insult differentially alter male and female baseline somatosensory thresholds and response to re-inflammation in adulthood?; (2) Are neonatal inflammation-induced deficits in nociceptive responsiveness mediated by a potentiation in endogenous opioid tone?; and (3) Does pre-emptive morphine analgesia attenuate the behavioral consequences of neonatal inflammatory insult? Collectively, these studies will provide valuable information about the long-term consequences of neonatal noxious stimulation in males and females, which may lead to improved understanding and prevention of the lasting effects of repeated invasive interventions in premature infants in the NICU.

Inhibition of angiogenesis is an effective and low toxic therapeutic avenue for the treatment of cancer patients in addition to traditional interventions. Majority of current available angiogenesis inhibitors for cancer therapies are growth factor inhibitors and small molecule tyrosine kinase inhibitors. A number of endogenous proteins and/or proteolytic fragments of extracellular matrix proteins are shown to have the activity of inhibition of angiogenesis by directly targeting endothelial cells. Structural analyses have indicated that a common structure of anti-parallel β-sheet with a highly positively charged surface presents in many of those inhibitors. This common structural feature is critical for the maintenance of their anti-angiogenic function. With this structural information, we have designed and developed a new class of anti-angiogenic proteins by integrating the short anti-parallel β-sheet forming sequences of endogenous anti-angiogenic proteins into a stable host protein, the extracellular domain-1 of cluster of differentiation 2 molecule (CD2D1). 1D 1H NMR spectra analyses indicated that the designed anti-angiogenic protein (ref to as ProAgio) folded as a β-sheet structure similar to that of the parental protein, CD2D1. ProAgio inhibited the growth of human umbilical vein cells (HUVECs) without affecting the growth of epithelial cells, suggesting a specific effect to endothelial cells. ProAgio effectively reduced endothelial tubules formed by the co-culture of HUVECs and PC3 cells on matrix gel in vitro. The designed anti-angiogenic protein was further site-specifically PEGylated in order to improve PK/PD properties and reduce immunogenicity. Examinations with PC3 xenografts showed that both ProAgio and the PEGylated ProAgio dramatically inhibited tumor growth. Immunofluorescence staining analyses of the endothelial marker CD31 indicated dramatic decreases in tumor vessels in lengths and branching points. Histological and immunofluorescence staining analyses of tissue slices of major organs indicated that there were no pathological damages to the tissue structure or disruption of normal vessels associated with the treatment of our designed anti-angiogenic agent. Overall, our studies developed a novel anti-angiogenesis agent that may have great clinical potentials. Our concept of protein design can be extended to the development of other novel protein drugs.

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.

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.

The mine dumps of Kiruna-type apatite-iron oxide ore in Bergslagen, South Central Sweden, contain elevated amounts of rare earth elements (REEs). A recently started project at Uppsala University has been initiated to study these ores among others in order to document occurrences of REEs and other critical elements in the mine dumps. In this study a selection of samples from the Idkerberget deposit have been studied with respect to their geochemistry and petrography with a special focus on REE-bearing phases. In addition, their mining potential and their relationship to related ore deposits such as Blötberget, Grängesberg and Kiirunavaara have been considered. The bulk geochemistry of the ores was analyzed using ICP-ES and ICP-MS. Polished sections of the ore samples were studied using ore microscopy, SEM-EDS and WDS microprobe technique. The results indicate that the ores consist mainly of magnetite and hematite, with minor silicates, flourapatite, pyrite, chalcopyrite, monazite-(Ce), allanite-(Ce), thorium silicate, titanite and zircon. Most REEs were originally hosted in flourapatite, but metamorphic and/or hydrothermal overprinting has resulted in complex textures and neomineralisation involving exotic REE-bearing minerals such as monazite-(Ce), allanite-(Ce) and secondary flourapatite. These features have also been observed in the related ore deposits nearby. The ores are enriched in REEs by factors between 1 and 9 compared to crustal values, with LREEs being the most enriched. These enrichments are rather low compared to other REE-ores currently being mined, but the easy access to the ores could mean that mining can be profitable with the current demand of these commodities. / Varphögar av apatitjärnmalm av Kirunatyp ifrån järnmalmsbrytning i Bergslagen, Sydcentrala Sverige, innehåller förhöjda halter av sällsynta jordartsmetaller. Ett projekt vid Uppsala Universitet undersöker förekomster av sällsynta jordartsmetaller och andra kritiska element i varphögar bland annat från apatitjärnmalmer. I denna studie har prover från ett av Bergslagens apatitjärnmalmsfält, Idkerberget, undersökts geokemiskt och petrografiskt med fokus på faser som innehåller sällsynta jordartsmetaller. Deras utvinningspotential och deras relation till liknande förekomster såsom Blötberget, Grängesberg samt Kiirunavaara har också tagits i beaktning. Bulkgeokemin i proverna analyserades med ICP-EM och ICP-MS. Polerprov av malmerna undersöktes medelst optisk mikroskopi, SEM-EDS samt med WDS-mikrosondteknik. Resultaten visar att malmerna framförallt består av magnetit och hematit, med mindre mängder silikater, flourapatit, pyrit, kopparkis, monazit-(Ce), allanit-(Ce), thoriumsilikat, titanit och zirkon. Sällsynta jordartsmetaller är i huvudsak bundna i flourapatit, men metamorfa och/eller hydrotermala processer har resulterat i nybildningen av exotiska mineral såsom monazit-(Ce), allanit-(Ce), och sekundär flourapatit. Dessa egenskaper har även observerats i apatitjärnmalmer från andra platser. Proverna från Idkerberget har 1-9 gånger högre koncentration av sällsynta jordartsmetaller än jordskorpan generellt, och lätta sällsynta jordartsmetaller är de mest anrikade. Dessa halter är relativt låga jämfört med sällsynta jordartsmalmer som bryts i dagsläget, men eftersom materialet förekommer i enorma varphögar gör tillgängligheten att metallerna ändå kan utvinnas med vinst om efterfrågan på denna resurs består.

This paper deals with the effects of minimum wages on human capital accumulation, and steady state employment and growth. The minimum wage is introduced in a model of endogenous growth driven by human capital accumulation. Unemployed agents maximize utility given the information that they are unemployed facing changed budget constraints. This situation is implemented in a "non-market-clearing equilibrium" framework. We show that the steady state rate of growth is not affected by the minimum wage and that in the steady state the system yields full employment. These effects are generated by intertemporal adjustments of the employed households who re-act to the relatively higher minimum wage which increases skills accumulation. (author's abstract) / Series: Department of Economics Working Paper Series

I present a simple model of an evolutionary financial market with heterogeneous agents, based on the concept of adaptive belief systems introduced by Brock and Hommes (1997a). Agents choose between different forecast rules based on past performance, resulting in an evolutionary dynamics across predictor choice coupled to the equilibrium dynamics. The model generates endogenous price fluctuations with similar statistical properties as those observed in real return data, such as fat tails and volatility clustering. These similarities are demonstrated for data from the British, German, and Austrian stock market. (author's abstract) / Series: Working Papers SFB "Adaptive Information Systems and Modelling in Economics and Management Science"