Focus on collagen: in vitro systems to study fibrogenesis and antifibrosis _ state of the art

Fibrosis represents a major global disease burden, yet a potent antifibrotic compound is still not in sight. Part of the explanation for this situation is the difficulties that both academic laboratories and research and development departments in the pharmaceutical industry have been facing in re-enacting the fibrotic process in vitro for screening procedures prior to animal testing. Effective in vitro characterization of antifibrotic compounds has been hampered by cell culture settings that are lacking crucial cofactors or are not holistic representations of the biosynthetic and depositional pathway leading to the formation of an insoluble pericellular collagen matrix. In order to appreciate the task which in vitro screening of antifibrotics is up against, we will first review the fibrotic process by categorizing it into events that are upstream of collagen biosynthesis and the actual biosynthetic and depositional cascade of collagen I. We point out oversights such as the omission of vitamin C, a vital cofactor for the production of stable procollagen molecules, as well as the little known in vitro tardy procollagen processing by collagen C-proteinase/BMP-1, another reason for minimal collagen deposition in cell culture. We review current methods of cell culture and collagen quantitation vis-à-vis the high content options and requirements for normalization against cell number for meaningful data retrieval. Only when collagen has formed a fibrillar matrix that becomes cross-linked, invested with ligands, and can be remodelled and resorbed, the complete picture of fibrogenesis can be reflected in vitro. We show here how this can be achieved. A well thought-out in vitro fibrogenesis system represents the missing link between brute force chemical library screens and rational animal experimentation, thus providing both cost-effectiveness and streamlined procedures towards the development of better antifibrotic drugs

Central Bank Financial Strength and Policy Performance

The financial health of central banks and its relation to policy outcomes has recently been recognized as an important policy issue. While case study evidence clearly indicates that weak central bank finances can hamper effective policy implementation, the question of whether central bank financial strength influences policy performance remains controversial. This is due, in part, to a lack of econometric evidence. The paper presents a first step toward filling this gap, by providing a quantitative evaluation of the relationship between measures of central bank financial strength and policy performance, in particular inflation. The paper''s major finding is that there indeed is a negative relationship between central bank financial strength and inflation outcomes. This relationship appears to be robust to the choice of alternative country samples, control variables, estimation strategies, and conceptualizations of central bank financial strength.Central bank autonomy;Economic indicators;central bank, inflation, central banks, monetary fund, monetary policy, monetary authorities, debt market, reserve requirements, debt management, reserve accumulation, monetary economics, domestic debt market, domestic debt, money demand, monetary policies, monetary policy decisions, intermediate monetary target, monetary institutions, debt accumulation, reserve holdings, monetary authority, reserve bank, monetary policy operations, public debt, external shock, monetary integration, market for government securities, monetary target, domestic public debt, long-term debt, domestic debt market development, money market, minimum reserve requirements, expansionary monetary policy, government securities

Policies to improve the local impact from hydrocarbon extraction: Observations on West Africa and possible lessons for Central Asia

The paper offers specific inputs to the debate on local content promotion in the oil industries of West Africa and Central Asia. To this end, we document the international experience with local content promotion to derive best practices in the field. We then use a case study approach to devise a simple analytical framework for rationalizing the selection of viable sectors for local content promotion, in an attempt to make operational one of the best practice principles (efficiency) developed before. By proposing specific rules regarding the acceptability of a project, the analysis seeks to add rigor and address distortions on localization outcomes from rent-seeking. The emphasis is not on supporting efforts to "pick winners" and subsidize them through a range of by and large discredited instruments. Rather, the paper focuses on the specific public inputs the government would have to provide to support an otherwise market-driven process.Local content policy Hydrocarbon extraction Input-output analysis

Inter-Sectoral Linkages and Local Content in Extractive Industries and Beyond

This paper attempts to offer specific inputs to the debate on local content promotion in the oil industry, using the specific case of São Tomé and Príncipe as point of reference. Our approach emphasizes inter-sectoral linkages and institutional pre-conditions for local content promotion. Based on an Input-Output description of the economy, we quantify the consistency between the prospective oil sector development and the growth of other sectors of the economy. We also assess a number of sectoral policies and "niche" activities within the oil industry that would maximize the local benefits from oil exploration.Oil sector;local content, oil and gas, oil industry, oil companies, gas industry, oil exploration, oil production, international oil companies, oil company, oil shock, oil exports, skilled labor, natural gas, natural resources, gas activities, oil fields, crude oil, million barrels, seismic data, oil & gas, transportation services, services sectors, gas production, downstream oil, petroleum sector, extractive industries, oil drilling, gas supply, petroleum law, gas development, production sharing contracts, domestic firms, environmental protection, offshore oil industry, million barrels per day, oil-producing countries, petroleum industry, service sector, engineering services, export markets, environmental services, comparative advantage, oil producing, oil and gas sector, oil transportation, downstream oil industry, offshore exploration, gas sector, petroleum products, gas business, upstream activities, preferential access, oil extraction, national oil, gas field, domestic industry, oil exporting countries, petrochemical industry, oil discoveries, oil traders, proven natural gas, foreign affiliates, petroleum regulations, onshore areas, oil industries, oil & gas industry, oil development, geological data, health services, petroleum company, petroleum extraction, human capital, trading services, imports of goods, oil supplies, economic point of view, gas extraction, petroleum corporation, business services, natural gas reserves, domestic demand, gas policy, financial services, offshore petroleum, exploration and production licenses, refined products, gas discoveries, crude oil production, gas producer, natural gas producer, gas reserves, insurance services, gas projects, well completion, exploration drilling, petroleum policy, gas supplier, opec, oil reserves, gas exploration, transport sectors, provision of services, oil refining, gas pipelines, exploration policy, oil storage, foreign capital, offshore oil fields, foreign employees, gas prices, petroleum development

Central Bank Response to the 2007-08 Financial Market Turbulence

The paper reviews the policy response of major central banks during the 2007–08 financial market turbulence and suggests that there is scope for convergence among central bank operational frameworks through the adoption of those elements that proved most instrumental in calming markets. These include (i) rapid liquidity provision to a broad range of counterparties; (ii) a congruence of collateral policies with market developments; (iii) an ability to increase the average maturity of liquidity provision; and (iv) central bank cooperation to facilitate the use of cross-border collateral. Flexible use of open market operations was needed to avoid the stigma associated with traditional standing facilities, and allowed central banks to maintain at least basic market functioning. Having a flexible framework, however, requires careful consideration of the desirable limits to market intervention.Monetary operations;Liquidity management;International cooperation;Financial risk;collateral, central bank, credit, monetary policy, pricing, money market, counterparty, repo, inflation, money markets, prices, refinancing, open market operations, national bank, pools, monetary fund, payments, government securities, payment system, discount rate, reserve requirements, purchases, monetary stance, payment systems, transmission of monetary policy, reserve requirement, holdings of government securities, cross border transactions, ccbm, systemic risk, government security, monetary base, monetary policy operations, monetary policy operation