Synthese des 18F-markierten Coenzyms Uridindiphosphatglucose als Basis für die 18F-Glykosylierung von Glykoproteinen

The chemo-enzymatic radiosynthesis of no carrier added (n.c.a.) uridine diphospho-2-deoxy- 2-[$^{18}$F]fluoro-$\alpha$-D-glucose (UDP-[$^{18}$F]FGlc) was developed. In order to overcome the problem of poor regioselectivity when using the commonly strategy to label proteins via $^{18}$F-labelled prosthetic groups, the use of enzyme systems in addition to the corresponding $^{18}$F-labelled coenzymes was shown to be a reliable, regioselective and mild labelling method. With regard to the comparison and evaluation of the stereoselectivity of the phosphorylating agents used in the chemical synthesis of cold uridine diphospho-2-deoxy-2-fluoro-$\alpha$-Dglucose, $^{31}$P-decoupled and $^{1}$H-NMR-studies were successfully realized. Uridine diphospho- 2-deoxy-2-fluoro-$\alpha$-D-glucose was obtained in a 7 step synthesis. Tetrabenzylpyrophosphate was shown to be a highly stereoselective phosphorylating agent for FDG ($\alpha /\beta$=3:1). Moreover, a multienzymatic pathway for the synthesis of uridine diphospho-2-deoxy-2-fluoro-$\alpha$- D-glucose was adopted starting from FDG and four commercially available enzymes. This strategy was adjusted to a mg-scale synthesis providing 35% chemical yield. Within the scope of this procedure, a comparison of the natural substrate $\alpha$-D-glucose-1-phosphate with 2-fluoro-2-deoxy-$\alpha$-D-glucose-1-phosphate indicated that the enzyme activity of UDP-glucose pyrophosphorylase (UDP-Glc PPase) was decreased by a factor of 30. With regard to the adaptability of the multiple enzyme system for the radiosynthesis of n.c.a. uridine diphospho-2-deoxy-2-[$^{18}$F]fluoro-$\alpha$-D-glucose a rapid hexokinase-mediated phosphorylation of [$^{18}$F]FDG utilizing ATP or UTP as phosphate donor was performed. A further enzymatic isomerization of n.c.a [$^{18}$F]FDG-6-phosphate to n.c.a. [$^{18}$F]FDG-1-phosphate was limited due to the formation of [$^{18}$F]FDG-1.6-diphosphate as main product. Experiments using a multiple enzyme system to develop a fully enzymatic synthetic route to UDP-[$^{18}$F]FGlc turned out to be less efficient due to the necessity of carrier added conditions. Thus, a chemo-enzymatic synthesis of n.c.a. UDP-[$^{18}$8F]FGlc has been developed, starting from 1.3.4.6-tetra-O-acetyl-2-[$^{18}$F]fluoro-2-deoxy-D-glucose, which occurs as an intermediate in the [$^{18}$F]FDG synthesis. The chemical phosphorylation via MacDonald reaction and subsequent deprotection led to a radiochemical yield of 55% of [$^{18}$F]FDG-1-phosphate. UDP- [$^{18}$F]FGlc was synthesized enzymatically by condensation of [$^{18}$F]FDG-1-phosphate with UTP in presence of UDP-Glc PPase. In order to overcome the problem of decreased enzyme acitivty the reaction was performed in a minimized reaction volume and optimized UTP-concentration of 0.5 mmol/l leading to an overall radiochemical yield of 20% of UDP-[$^{18}$F]FGlc within 110 min. The $^{18}$F-labelled coenzyme UDP-[$^{18}$F]FGlc was used as a tool for $^{18}$F-glycosylation of N-acetylglucosamine mediated by $\beta$-1.4-galactosyltransferase. The $^{18}$F-glycosylated product was obtained in a radiochemical yield of 56% and was easily isolated by solid phase extraction. In addition to the general availability of [$^{18}$F]FDG worldwide, this new strategy for enzymatic transfer of "activated [$^{18}$F]FDG" has demonstrated its potential as a highly selective and mild $^{18}$F-labelling method of glycosylated biopolymers to study their pharmacokinetics using positron-emission-tomography

A Primer on Profit Maximization

Although textbooks in intermediate microeconomics and managerial economics discuss the first-order condition for profit maximization (marginal revenue equals marginal cost) for pure competition and monopoly, they tend to ignore the second-order condition (marginal cost cuts marginal revenue from below). Mathematical economics textbooks also tend to provide only tangential treatment of the necessary and sufficient conditions for profit maximization. This paper fills the void in the textbook literature by combining mathematical and graphical analysis to more fully explain the profit maximizing hypothesis under a variety of market structures and cost conditions. It is intended to be a useful primer for all students taking intermediate level courses in microeconomics, managerial economics, and mathematical economics. It also will be helpful for students in Master’s and Ph.D. programs in economics and in MBA programs. Moreover, the paper provides instructors with an effective supplement when explaining the profit-maximization concept to student

Evaluating coasean bargaining experiments with meta-analysis

While the Coase Theorem has been a touchstone for understanding bargaining behavior, it has also been criticized for relying on unrealistic assumptions. In response, a line of experimental research analyzes bargaining behavior in laboratory settings. This paper uses meta-analysis to evaluate the Coasean bargaining literature by modeling the probability of an efficient bargain as a function of: (1) measures of transaction costs and related variables, and (2) measures of the social dimensions of a bargain. Results suggest that efficient solutions are more likely when explicit transaction costs do not exist, in the absence of a binding time limit, and when participants have perfect information on payoff schedules. Social dimension variables are found to have the potential to affect bargaining outcomes and are an important avenue for further research.Coase Theorem

A DIMENSÃO DE GÊNERO NA POLITICA DE ASSISTÊNCIA SOCIAL

Resumo Este artigo aborda a Política de Assistência Social a partir da Proteção Social Especial de Média Complexidade, apresentando resultados parciais de pesquisa social, orientada pelo método dialético-crítico, realizada nos Centros de Referência Especializados de Assistência Social – CREAS da Região Funcional de Planejamento 9 do Estado do Rio Grande do Sul. Os CREAS foram analisados de modo a identificar de que forma a perspectiva de gênero está presente na política de assistência social e como se materializa essa perspectiva no discurso dos profissionais. Para isto, foram verificados a estrutura física, material e de recursos humanos; a organização e metodologia dos serviços ofertados; e, as seguranças sociais que a proteção social de Assistência Social visa garantir à população usuária. Esta pesquisa indicou que as ações realizadas nos CREAS perpetuam estereótipos de gênero, não sendo materializado o princípio da matricialidade sociofamiliar

Independent Evaluation of the Partnership Committees of the CGIAR : Final Report

This study was undertaken as part of the CGIAR reform program, part of which was aimed at streamlining System governance. The CGIAR Annual General Meeting 2002 agreed to commission an independent, external review of both the Non Governmental Organization Committee (NGOC) and the Private Sector Committee (PSC). The terms of reference for the study asks two questions: 1) how successful have the Committees been in achieving their mission? and 2) are there alternative ways in which the CGIAR could achieve the Committees' mission more efficiently? The evaluation recognized that the two committee experiment in partnerships was generally disappointing to all parties but it nevertheless wishes to underscore the importance of persevering with the experiment. The report underlines the importance for strong relationships between the CGIAR system and international Civil Society as well as the relationship between the CGIAR system and the international private sector. The report was discussed at the 6th Executive Council Meeting of the CGIAR, in May 2004, Montpellier, France. It was also discussed at the Stakeholders Meeting at AGM2004

Inducing Private Wildfire Risk Mitigation: Experimental Investigation of Measures on Adjacent Public Lands

Increasing private wildfire risk mitigation is an important part of the larger forest restoration policy challenge. Data from an economic experiment are used to evaluate the effectiveness of providing fuel treatments on public land adjacent to private land to induce private wildfire risk mitigation. Results show evidence of “crowding out” where public spending can decrease the level of private risk mitigation. However, a policy prescription that ameliorates this crowding out is identified. Participants undertake more mitigation when fuel treatments on publicly owned lands are conditional on a threshold level of private mitigation effort and information describing each participant’s spending is provided. Key Words: