Quinone Reductase 2 is a Flavin Redox Switch

Quinone reductase 2 (NQO2) is a mammalian enzyme that catalyzes the reduction of quinone using an unusual co-substrate, dihydronicotinamide riboside (NRH). In addition, NQO2 has a secondary function, which is to modulate the 20S proteasomal degradation of p53 in a redox-dependent manner. This alternate function has been characterized in its sister enzyme quinone reductase 1 (NQO1) and yeast quinone reductase Lot6p, but relatively few studies have investigated the role of NQO2 beyond quinone catalysis. From studies of Lot6p, it was proposed that quinone reductases could be categorized as flavin redox switches. In this thesis, the how NQO2 functions as a flavin redox switch and how inhibitors can modulate NQO2 was investigated. Initially, a method was developed to reconstitute recombinant NQO2 with FAD. Having purified functional NQO2, reduced structures of NQO2 were solved in complex with four different inhibitors: the antimalarial drug chloroquine, CK2 inhibitor DMAT, DNA intercalating agent ethidium bromide, and acridine orange. In all four reduced structures, the hydrogen bond network and the orientation of inhibitors in the active site of NQO2 were changed by the presence of water molecules compared to the oxidized structures. For the structure of reduced NQO2 in complex with chloroquine, there was also a global conformational change. These reduced structures together showed that NQO2 has two functional states, and indicated mechanistic features of a flavin redox switch in NQO2. To understand how these inhibitors affect NQO2 signalling in cells, the CK2 inhibitors and DNA intercalating agents were further studied in tissue culture. Even though the cytotoxicity of these compounds was not dependent on NQO2, p53 levels were modulated in an NQO2-dependent manner. In conclusion, this thesis has shown that in addition to quinone catalysis, NQO2 functions as a flavin redox switch, and NQO2 inhibitors have the ability to modulate this process

Protectionism Actually Hurts U.S. Jobs And Economy: An Investigation Of Proponents And Opponents

Outsourcing is an issue that is generating a lot of debate in the Pacific Northwest, often in response to stories about job cuts and fears that workers will get left out in the cold. However, much of what we read and hear about outsourcing is based on misinformation, no information, or just plain politics. Every major national study confirms that outsourcing creates more jobs than it destroys in the U.S. One of the most persistent complaints against globalization is that it destroys jobs. Many people believe that, the more shoes or cars or steel beams we import to the U.S., the fewer we produce ourselves and the fewer Americans with jobs in those industries. Anxiety about trade and jobs is especially acute about imports from poor countries, where workers typically earn a fraction of the wages earned by American workers. The most ardent proponents of free trade will grant that its benefits are not universally distributed, while it almost always outweighs the costs. Along with the many winners come smaller but still real numbers of losers: people whose jobs are indeed put in jeopardy and even eliminated by competition from imports. For those people, the benefits of lower prices, higher quality, and wider consumer choices can be swamped, at least temporarily, by the trauma of losing their jobs. The purpose of this research is to investigate the advantages and disadvantages of protectionism and its impacts on U.S. jobs and the economy

E-Commerce In China And Its Risks And Opportunities For US Companies

China is the fastest growing Internet economy in Asia/Pacific, with Chinese Internet users forecasted to account for approximately half of all Internet usage in the region by the end of 2005. Chinese companies are also proving to be the largest investors of Internet infrastructure equipment as they turn to the Internet to increase business and information flow. As the Internet permeates all corners of the globe, small to medium-sized businesses may be pondering the move to a multilingual ecommerce website to increase their reach, and may be enticed by the potentially huge Chinese market. While a larger corporation can make the transition to a multilingual site with relative ease, small to medium enterprises (SMEs) must be concerned about the cost and effort involved, as well as how to go about the actual translation process and handle complications. China’s accession into the World Trade Organization (WTO) has opened up many opportunities, especially to expand their operations in the outside world, and has also changed it from a minor trading country to one of the world’s major trading countries. Some companies are already starting to take advantage of these opportunities, making now the key time to get a foothold in the market before everyone else makes their claim. The countries as a whole and its individual companies begin to face a range of issues that will have a direct impact on the course of the country’s further development. This research paper will examine business environment in China for US companies to analyze risks and opportunities of E-commerce in China

The role of phonology in Chinese characters recognition : the influence of experimental tasks

In order to explore the role that phonology play in Chinese characters recognition, 9 variables at lexical level (i.e. character frequency, number of words formation) and sub-lexical level (i.e. number of strokes, regularity, phonological consistency, family size) were used to predict their effects on Chinese lexical decision time by stepwise multiple regression analysis. The result showed that phonology played a significant role in feedback activation (i.e. homophones density and number of associated radicals) but not in feedforward activation. Moreover, we revealed differences in the cognitive process between lexical decision task and naming task. Since those task-specific properties may affect the result obtained, we further suggested that it should be careful in task selection and data interpretation in future psycholinguistic research.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Schools as spaces for in/exclusion of young Mainland Chinese students and families in Hong Kong

Around 30,000 children living in Shenzhen, Mainland China cross the border to Hong Kong to attend school every day. This paper focuses on the school as a key meso-level organisation that mediates macro-level policies and micro-level everyday life experiences among these children and their families. We advocate a relational, spatial perspective, conceptualising schools as webs of intersecting physical, social and digital spaces, where differences between the “locals” and “others” are played out, negotiated and (re)produced, and in turn giving rise to specific (and understudied) geographies of in/exclusion. Drawing on our qualitative research, we offer a close reading of three exemplary school spaces: (i) the physical classroom and school grounds, (ii) the digital classroom, and (iii) at the school gate. Our findings demonstrate the complex and at times contradictory ways in which “the school” is a place of both inclusion and exclusion. It is a dynamic and power-traversed space where social differences between the “locals” and the “others” are played out, contested and redefined continuously

Antidumping Charges Against China: A Comprehensive Analysis Of Proponents, Opponents, And Its Impact On U.S. Companies

Few nations have changed as fast—or as Dramatically—as China has since the 1970s. The world’s most populous nation has radically liberalized its economy and gone from producing low-quality and simple export to sophisticated high- technology goods, while nurturing a vibrant private sector and attracting nearly $500 billion in foreign direct investment (FDI). China’s total exports grew eightfold—to over$380 billion—between 1990 and 2003. China’s share of global exports will reach 6 percent in 2003, compared to 3.9 percent in 2000. The U.S. has lost about 2.6 million manufacturing jobs since 2001. While private economists say that most of he job losses reflected improved productivity at U.S. factories, many in Congress and within industry say China blame China. China’s soaring economy has turned it into manufacturing juggernaut that maintains the largest trade surplus of many nations, including the U.S. U.S. law provides for the protection of American manufacturers form unfair foreign trade practices. If U.S. companies believe that foreign competitors are dumping merchandise in the U.S. or are being subsidized by foreign governments, they may file for relief with the U.S. Department of Commerce’s International Trade Administration and the U.S. Trade Commission.  Antidumping levies duties on goods dumped on the U.S. market. One of the most contested issues is whether U.S. trade laws, in particular the antidumping laws, should be open to negotiation. It should for the benefits of U.S. customers and U.S. businesses.  This research will focus on dumping charges against China and evaluate pros and cons of U.S. antidumping laws against foreign companies and its impact on U.S. consumers and businesses

The effects of two types of sports mouthguards on speech intelligibility

"A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, April 30, 2003."Thesis (B.Sc.)--University of Hong Kong, 2003.Also available in print.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Anti-Inflammatory Protein of Schistosoma japonicum Directs the Differentiation of the WEHI-3B JCS Cells and Mouse Bone Marrow Cells to Macrophages

Sj16 is an anti-inflammatory protein identified from Schistosoma japonicum. Our previous studies showed that recombinant Sj16 (rSj16) could suppress host's inflammatory responses and inhibit macrophage maturation. In the present study, the effects of rSj16 on the differentiation of the murine myeloid leukemia WEHI-3B JCS cell line and on mouse hematopoiesis were investigated. Our data demonstrated that rSj16 expressed and purified from Escherichia coli could suppress the proliferation of the WEHI-3B JCS cells in a time- and concentration-dependent manner, while not affect the viability of the cells. Further studies indicated that rSj16 induced macrophage differentiation of the WEHI-3B JCS cells, and arrested the cell cycle in the G1/G0 and G2/M phases. The macrophage differentiation of the rSj16-treated WEHI-3B JCS cells was confirmed by their expression of macrophage specific antigen F4/80 and phagocytic activity. Furthermore, our results revealed that rSj16 biased the colony formation of mouse bone marrow cells towards macrophage linage