Wendy Dobson

Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

BackgroundRNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK) family of SR protein kinases on HIV-1 expression and RNA processing was examined.ResultsDespite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication.ConclusionsTogether, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.

Governance, Multinationals and Growth

Foreword by Peter J. Buckley Part I: Introduction Part II: Corporate Governance, Multinationals and Growth Part III: Free Trade, Multinationals and Growth Part IV: Public Governance, Multinationals and Growth Part V: Conclusions Index.

Deeper Integration in East Asia: Regional Institutions and the International Economic System

SEA change in East Asian perceptions of the international economic system is causing a determined thrust toward deeper East Asian integration through regional financial and trade institutions. The financial crisis of 1997‐98 contributed to this change by revealing weaknesses in the international financial architecture at the same time that it bared weaknesses in domestic policies and institutions in East Asia. Many East Asians felt the existing international financial system failed to provide them with adequate prescriptions or aid at a time of great need. In response, governments are intensifying regional policy cooperation and have begun to develop regional institutional capacity to head off future financial crises and manage them if they occur. This change in perceptions of the international economic system has been reinforced by paralysis in the World Trade Organisation (WTO). The failure of governments to launch a new round of multilateral trade negotiations at the November 1999 WTO ministerial meeting in Seattle is helping to propel regional approaches to trade liberalisation. Deeper integration in East Asia is a potentially substantial development, which will influence the future shape of the international economic system. In Section 2, I review the primary factors contributing to the financial crisis and discuss the implications for policy makers in East Asia, in a context of diminished confidence in global institutions. The emphasis is on macroeconomic policy management, structural reforms, changing incentive systems, overhauling crisis

East Asian capitalism : diversity and dynamism

* Preface*The diversity and dynamism of capitalism in East Asia - A.E. Safarian and Wendy Dobson*The organization of capitalism in South Korea and Taiwan - Gary G. Hamilton*The paradox of Chinas industrial reform - Gary H. Jefferson and Thomas G. Rawski*Southeast Asian business systems: The dynamics of diversity - Linda Lim*Hidden linkages in Japanese business - Richard W. Wright

Window of Opportunity Opens: Asian and American Views of the International Economic Architecture

This paper compares US and Asian views of the international economic architecture including Asia’s evolving regional institutions. Lessons from the global financial crisis are used to assess reforms of the financial institutions better to prevent and manage future crises. While G20 leaders have increased the resources of the International Monetary Fund much work remains to restore its legitimacy and independence and to define clearly the Financial Stability Board’s mandate to strengthen financial oversight and regulation. The paper critiques proposals for a global super-regulator and concludes that while the global architecture is important, the tests of its success will be fewer government actions to self-insure and the willingness to heed warnings of future problems and take timely corrective actions.

THE MACDONALD REPORT: SIGNPOST OR SHOPPING BASKET?

he Report of the Royal Commission on the Economic Union and Development Prospects for Canada is a landmark in the evolution of Canadian economic policy. The Commission started its work in the depths of a serious recession with an unwieldy mandate and thirteen Commissioners drawn from varied backgrounds. During the nearly three years of its existence, the Commission held wide-ranging public hearings and the staff did considerable research aimed at synthesizing the state of existing knowledge relating to its mandate in economics, political science, and law. An interim report, published in April 1984, lacked focus on possible solutions and created confusion about the Commissions view of the nature of, and reasons for, Canadas economic predicament. The final Report, however, is a remarkable document. Forceful recommendations for far-reaching changes in the conduct of Canadian economic policy replace earlier lack of focus and confusion. Together, the recommendations provide a signpost signaling a volte face in the way Canadians should look at their economy; singly or in groups, they present a shopping basket of proposals for change. We see three important themes that underlie the Commissions economic policy analysis and that give unity to its recommendations: Canada is a small open economy operating in an increasingly turbulent and uncertain international environment; its preeminence as a producer of natural resources has declined:

Deeper Integration between Canada and India

Relative to their economic sizes, structures and linkages, the bilateral relationship between Canada and India is too small. Trade and foreign direct investment (FDI) flows are gradually increasing within such sectors as finance, energy, power and environmental services, agriculture and information technology (IT) services. Two channels are identified to expand this economic footprint: deeper linkages among bilateral business groups to reduce Canadians’ transactions costs relative to those in the United States (US) market; and improved market access for India’s competitive low-cost producers. Governments, which focus primarily on incremental improvements, should elevate the bilateral relationship to a strategic level with the negotiation of a free trade agreement (FTA). Although each government prefers the World Trade Organization (WTO) as the venue for liberalising agricultural trade, it is argued that a services-only FTA would yield mutual gains by removing many of the restrictions affecting both domestic markets and foreign entrants in the two countries revealed by the comparative analysis in this paper.

The Indian Elephant Shed its Past: The Implications for Canada

India is a land of contrasts. Indian information technology (IT) services firms are globally competitive but many manufacturers still seek protection from foreign competitors. Economic growth rates are speeding up but trade is still a small share of the world total. Logistics infrastructure is abysmal. India has the most mature and diverse financial system in the emerging market economies and many excellent universities, but the government seeks to create 100 million industrial jobs in this decade to provide employment for its 400-million-strong work force, many of whom are still illiterate.As serious attempts are made to tackle its weaknesses and build on its strengths, India is broadening its economic reforms and establishing itself as a high-growth emerging market. Canada should be moving more quickly to deepen the bilateral economic relationship. Two-way merchandise trade flows are small. But mutual interest is growing to provide services, both directly to each other and from platforms in both countries, to serve larger regional and global markets.While Canadas economic future will be determined mainly by its proximity to the United States, more could be made of the bilateral relationship with India. The two countries share many of the same institutions and language of commerce because of their common colonial heritage. There is a sizeable Indian diaspora in Canada. Business ties will continue to grow, but incrementally, unless governments facilitate this mutual interest. They should consider negotiating a bilateral free trade agreement - either in services or across the board. Canadian interest would likely focus on greater across-the-board access for Foreign Direct Investment (FDI) in India, while Indians would likely push for liberalization of cross-border services provision and the movement of people. India has developed a mechanism, the Joint Study Group, for evaluating the net benefits of FTAs with other potential partners; the two countries should also take this step.

Beyond FTAs: Deepening North American Integration

This paper presents a Canadian perspective on North American integration in the light of major changes in the world economy since the implementation more than a decade ago of the Canada-US FTA and the NAFTA. These changes highlight the need for completion of these FTA projects by totally eliminating tariffs and other border barriers and pursuing deeper economic integration that respects and preserves national sovereignty. It begins with a view of these changes. It then explores the challenges for North America as China and India become major players in global production systems in manufacturing and services and follows with an analysis of some of the implications for North American integration. It concludes that the rapid rise of China and India should be a catalyst for deeper integration in North America and, indeed, for a single market in the hemisphere.

Summitry and the international monetary system: The past as prologue

The article begins by noting the role of the Summits in meeting an implicit demand for policy coordination among Summit participants. It details the evolution of the Summit from a forum to set initiatives to an occasion for issue identification. The discussion then moves to consider the growing challenges to the ability of governments to regulate the international monetary system in the face of an increasing vital private sector. Several suggestions for reform are offered to facilitate a more effective international monetary system and a more relevant G7 Summit. Opportunities for a more “business‐like” Summit are examined including greater economic coordination among Summit members and the creation of mechanisms for the broader participation of “star economic performers” which are not included in the G7.