Biochemical and Spectroscopic Characterization of Tryptophan Oxygenation: Tryptophan 2, 3-Dioxygenase and Maug

TDO utilizes b-type heme as a cofactor to activate dioxygen and insert two oxygen atoms into free L-tryptophan. We revealed two unidentified enzymatic activities of ferric TDO from Ralstonia metallidurans, which are peroxide driven oxygenation and catalase-like activity. The stoichiometric titration suggests that two moles of H2O2 were required for the production of one mole of N-formylkynurenine. We have also observed monooxygenated-L-tryptophan. Three enzyme-based intermediates were sequentially detected in the peroxide oxidation of ferric TDO in the absence of L-Trp including compound I-type and compound ES-type Fe-oxo species. The Fe(IV) intermediates had an unusually large quadrupole splitting parameter of 1.76(2) mm/s at pH 7.4. Density functional theory calculations suggest that it results from the hydrogen bonding to the oxo group. We have also demonstrated that the oxidized TDO was activated via a homolytic cleavage of the O-O bond of ferric hydroperoxide intermediate via a substrate dependent process to generate a ferrous TDO. We proposed a peroxide activation mechanism of the oxidized TDO. The TDO has a relatively high redox potential, the protonated state of the proximal histidine upon substrate binding as well as a common feature of the formation of ferric hydroxide species upon substrate or substrate analogues binding. Putting these together, we have proposed a substrate-based activation mechanism of the oxidized TDO. Our work also probed the role of histidine 72 as an acid-base catalyst in the active site. In H72S and H72N mutants, one water molecule plays a similar role as that of His72 in wild type TDO. MauG is a c-type di-heme enzyme which catalyze the biosynthesis of the protein-derived cofactor tryptophan tryptophylquinone. Its natural substrate is a monohydroxylated tryptophan residue present in a 119-kDa precursor protein of methylamine dehydrogenase (MADH). We have trapped a novel bis-Fe(IV) intermediate from MauG, which is remarkably stable. A tryptophanyl radical intermediate of MADH has been trapped after the reaction of the substrate with the bis-Fe(IV) intermediate. Analysis by high-resolution size-exclusion chromatography shows that MauG can tightly bind to the biosynthetic precursor and form a stable complex, but the mature protein substrate does not

Essays on macro-finance

This thesis on topics in macro-finance, considers the relationship between the macro economy and also financial marets. We examine the key predictors, including macro determinants and technical indicators, of returns to the US stock market. Moreover, we investigate the links between financial markets internationally. We also study the importance of financial factors for monetary policy. In more detail, Chapter 2 constructs a flexible Bayesian framework to predict the equity premium, allowing for abrupt or gradual or even no changes in forecasting models and in coefficients. This approach has out-of-sample predictive power statistically and economically. Moreover, this model dominates its nested combination methods, including equal-weighted models, Bayesian and dynamic model averaging. By decomposing the prediction variance, we find that our approach precisely identifies the locally appropriate time variation in coefficients and the forecasting model over time, leading to mitigation of estimation risk. We then go on in Chapter 3 to model and predict financial integration, given the rapidly evolving nature of financial globalization. Importantly, this chapter allows national exposure to the global financial factors and the process driving volatility to vary over time. The obtained results show that financial integration is highly predictable, which has implications for international diversification, risk management and policy making. The CBOE volatility index (VIX) is identified as a strong predictor of financial integration, reflecting the vulnerability of financial markets to uncertainty. Our third main chapter, Chapter 4 studies how the impact of monetary policy shocks interact with the financial environment, in particular with financial uncertainty. The work identifies that monetary shocks have stronger, but less persistent, effects during periods of elevated financial uncertainty compared to more tranqil periods. These differences in effects among the uncertainty dependent states suggest that nonlinearities in the credit channel are stronger in the short run, whereas in the long run nonlinearities in the interest rate channel dominate

Early parental loss, socioeconomic stressors, and health in later life: Evidence for gender disparity

Drawing from the stress process model and the cumulative disadvantage theory, this dissertation examined how childhood and later life stressors affected cognitive and subjective health in older adults. Using three main articles, this dissertation investigated (1) the effect of early parental loss on cognitive well-being in Chinese oldest old; (2) the effect of intergenerational socioeconomic mobility on cognitive and subjective health in advanced age; and (3) the effect of different dimensions of socioeconomic status and perceived financial strain on subjective health in later life. Data were derived from the 2002 and 2005 waves of the Chinese Longitudinal Healthy Longevity Survey. Ordinary least squares models and logistic regression models were used to estimate the stress-health association. Key findings of this dissertation include (1) losing a mother in early life predicted worse cognitive function in oldest old men; (2) experiencing downward intergenerational socioeconomic mobility was detrimental to cognitive and subjective health in advanced age, especially in oldest old women; and (3) perceived financial strain was associated with an elevated risk of reporting poor health for both urban and rural inhabitants. Findings of this dissertation suggest that traumatic events in early life and socioeconomic stressors in later life both exact a toll on Chinese older adults’ health, independent of their demographic characteristics and physical health conditions. This dissertation has policy implications for gender-specific healthcare

Health Care System Reform in China: Issues, Challenges and Options

This paper examines health care reform in urban and rural China. Before health care reform, Chinese health service facilities were run entirely by the state and basically they performed a social welfare function. This health care system greatly improved the population health conditions but many problems started to emerge in 1980s when the economic reform started. Since then, the government has been struggling to maintain a balance between meeting people¡¯s health care needs and develop the health care "industry". Problems and their contribution factors in organization, financing and performance of the health care reform are examined and analyzed. In terms of organization, decentralization of the decision making power in health sector and marketization of the medical establishments constitutes the main organizational changes in the health care reform. This organizational reform of health sector as an imposed institution change, encounters lots of resistance in the process of implementation. A tremendous amount of conflictions arises because of the commercialization of health sector that used to perform social welfare function. In terms of financing, share of organized financing (government and social fund) in the total health expenditure declined dramatically since the reform. In urban China, Health care insurance faced tough going on universal access. In rural China, there are lots of problems in implementing new cooperative health system partly because of its imperfect design. In terms of performance, data shows that there is growing inequity in health status between rural and urban in the past 15 years. Inefficiencies also exists in both resource allocation and service delivery. Several options are analyzed for organizational reform and health care financing. The report recommends that the aims of the future reform policy that government would adopt should be to improve the population health status instead of generating profit for institutions or industry. The social welfare function of health care system should be reinforced and at the same time managed competition in the health care market should be encouraged. In health care financing in urban area, several directions of broadening risk pooling are discussed. In rural health care financing, the designing of new cooperative health care system is analyzed. Rural financing should be more flexible in order to attract more people to join the cooperative medical system. It is recommended that Chinese government should increase funding for public health programs and subsidize health services for the disadvantaged groups.

An Empirical Analysis of Profitability Determinants and Cost Efficiency of Commercial Banks in China

Abstract During the period 2009-2014, the overall performance of China’s banking sector is decline. The recession is mainly due to the international and Chinese economic turmoil. The purpose of this study is to investigate the determinants of profitability and cost efficiency for 30 commercial banks operating in China during the examination period 2009-2014. Under the estimation of GMM, all bank-specific determinants have a positive relationship with bank performance, while all macroeconomic factors are negatively correlated with profitability. Cost efficiency, which is one of the essential determinants of interpreting bank profitability estimated by SFA shows a decline over time