Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) have been identified as ligands with different effector functions of the vascular assembly and maturation-mediating receptor tyrosine kinase Tie-2. To understand the molecular interactions of the angiopoietins with their receptor, we have studied the binding of Ang-1 and Ang-2 to the Tie-2 receptor. Enzyme-linked immunosorbent assay-based competition assays and co-immunoprecipitation experiments analyzing the binding of Ang-1 and Ang-2 to truncation mutants of the extracellular domain of Tie-2 showed that the first Ig-like loop of Tie-2 in combination with the epidermal growth factor (EGF)-like repeats (amino acids 1-360) is required for angiopoietin binding. The first Ig-like domain or the EGF-like repeats alone are not capable of binding Ang-1 and Ang-2. Concomitantly, we made the surprising finding that Tie-2 exon-2 knockout mice do express a mutated Tie-2 protein that lacks 104 amino acids of the first Ig-like domain. This mutant Tie-2 receptor is functionally inactive as shown by the lack of ligand binding and receptor phosphorylation. Collectively, the data show that the first 104 amino acids of the Tie-2 receptor are essential but not sufficient for angiopoietin binding. Conversely, the first 360 amino acids (Ig-like domain plus EGF-like repeats) of the Tie-2 receptor are necessary and sufficient to bind both Ang-1 and Ang-2, which suggests that differential receptor binding is not likely to be responsible for the different functions of Ang-1 and Ang-2.

Price risk management in the copper market using commodity derivatives and options strategies

Metals price risk management is a key issue related to financial risk in metal markets because of uncertainty of commodity price fluctuation, exchange rate, interest rate changes and huge price risk either to metals’ producers or consumers. Thus, it has been taken into account by all participants in metal markets including metals’ producers, consumers, merchants, banks, investment funds, speculators, traders and so on. Managing price risk provides stable income for both metals’ producers and consumers, so it increases the chance that a firm will invest in attractive projects. The purpose of this research is to evaluate risk management strategies in the copper market. The main tools and strategies of price risk management are hedging and other derivatives such as futures contracts, swaps and options contracts. Hedging is a transaction designed to reduce or eliminate price risk. Derivatives are financial instruments, whose returns are derived from other financial instruments and they are commonly used for managing financial risks. Although derivatives have been around in some form for centuries, their growth has accelerated rapidly during the last 20 years. Nowadays, they are widely used by financial institutions, corporations, professional investors, and individuals. This project is focused on the over-the-counter (OTC) market and its products such as exotic options, particularly Asian options. The first part of the project is a description of basic derivatives and risk management strategies. In addition, this part discusses basic concepts of spot and futures (forward) markets, benefits and costs of risk management and risks and rewards of positions in the derivative markets. The second part considers valuations of commodity derivatives. In this part, the options pricing model DerivaGem is applied to Asian call and put options on London Metal Exchange (LME) copper because it is important to understand how Asian options are valued and to compare theoretical values of the options with their market observed values. Predicting future trends of copper prices is important and would be essential to manage market price risk successfully. Therefore, the third part is a discussion about econometric commodity models. Based on this literature review, the fourth part of the project reports the construction and testing of an econometric model designed to forecast the monthly average price of copper on the LME. More specifically, this part aims at showing how LME copper prices can be explained by means of a simultaneous equation structural model (two-stage least squares regression) connecting supply and demand variables. A simultaneous econometric model for the copper industry is built: {█(Q_t^D=e^((-5.0485))∙P_((t-1))^((-0.1868) )∙〖GDP〗_t^((1.7151) )∙e^((0.0158)∙〖IP〗_t ) @Q_t^S=e^((-3.0785))∙P_((t-1))^((0.5960))∙T_t^((0.1408))∙P_(OIL(t))^((-0.1559))∙〖USDI〗_t^((1.2432))∙〖LIBOR〗_((t-6))^((-0.0561))@Q_t^D=Q_t^S )┤ P_((t-1))^CU=e^((-2.5165))∙〖GDP〗_t^((2.1910))∙e^((0.0202)∙〖IP〗_t )∙T_t^((-0.1799))∙P_(OIL(t))^((0.1991))∙〖USDI〗_t^((-1.5881))∙〖LIBOR〗_((t-6))^((0.0717) Where, Q_t^D and Q_t^Sare world demand for and supply of copper at time t respectively. P(t-1) is the lagged price of copper, which is the focus of the analysis in this part. GDPt is world gross domestic product at time t, which represents aggregate economic activity. In addition, industrial production should be considered here, so the global industrial production growth that is noted as IPt is included in the model. Tt is the time variable, which is a useful proxy for technological change. A proxy variable for the cost of energy in producing copper is the price of oil at time t, which is noted as POIL(t ) . USDIt is the U.S. dollar index variable at time t, which is an important variable for explaining the copper supply and copper prices. At last, LIBOR(t-6) is the 6-month lagged 1-year London Inter bank offering rate of interest. Although, the model can be applicable for different base metals' industries, the omitted exogenous variables such as the price of substitute or a combined variable related to the price of substitutes have not been considered in this study. Based on this econometric model and using a Monte-Carlo simulation analysis, the probabilities that the monthly average copper prices in 2006 and 2007 will be greater than specific strike price of an option are defined. The final part evaluates risk management strategies including options strategies, metal swaps and simple options in relation to the simulation results. The basic options strategies such as bull spreads, bear spreads and butterfly spreads, which are created by using both call and put options in 2006 and 2007 are evaluated. Consequently, each risk management strategy in 2006 and 2007 is analyzed based on the day of data and the price prediction model. As a result, applications stemming from this project include valuing Asian options, developing a copper price prediction model, forecasting and planning, and decision making for price risk management in the copper market.

The rate of outpatient cataract surgery in ten European countries: an analysis using data from the SHARE survey

BACKGROUND: The aim of this study was to determine the rates of outpatient cataract surgery (ROCS) in ten European countries and to find country-specific health indicators explaining the differences. METHODS: Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE), 251 eligible respondents were identified for which cataract surgery was the last surgical procedure. The ROCS of ten countries were compared using logistic regression. The influence of the public expenditure on health as per cent of the total expenditure on health, of the number of acute care beds per 1,000 population, and of the number of practicing physicians per 1,000 population, was studied by multiple logistic regression. Additional information was obtained from country-specific opinion leaders in the field of cataract surgery. RESULTS: The ROCS differed significantly between the ten analysed European countries where Denmark had the highest (100%) and Austria the lowest (0%) rate of day care surgery. A decrease in the density of acute care beds (p < 0.0000001) and in the density of practicing physicians (p < 0.05) and an increase in the public expenditure on health as per cent of the total health expenditure (p < 0.01) lead to an increase in the ROCS. According to the opinion leaders, regulations and financial incentives also have a strong influence on the ROCS. CONCLUSIONS: The outpatient rate of cataract surgery in the ten European countries was mainly influenced by the acute-care beds density, but also by the density of practicing physicians, and by the public expenditure on health.

Waiting times for cataract surgery in ten European countries: an analysis using data from the SHARE survey

AIMS: To assess waiting times for cataract surgery and their acceptance in European countries, and to find explanatory, country-specific health indicators. METHODS: Using data from the survey of health, ageing and retirement in Europe (SHARE), waiting times for cataract surgery of 245 respondents in ten countries were analysed with the help of linear regression. The influence of four country specific health indicators on waiting times was studied by multiple linear regression. The influence of waiting time and country on the wish to have surgery performed earlier was determined through logistic regression. Additional information was obtained for each country from opinion leaders in the field of cataract surgery. RESULTS: Waiting times differed significantly (p<0.001) between the ten analysed European countries. The length of wait was significantly influenced by the total expenditure on health (p<0.01) but not by the other country specific health indicators. The wish to have surgery performed earlier was determined by the length of wait (p<0.001) but not by the country where surgery was performed. CONCLUSION: The length of wait is influenced by the total expenditure on health, but not by the rate of public expenditure on health, by the physician density or by the acute bed density. The wish to have surgery performed earlier depends on the length of wait for surgery and is not influenced by the country.

What Price Social and Health Care? Commodities, Competition and Consumers

In this paper we explore some important disputes and problems surrounding the legal status and social purpose of Health