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

Longitudinal Analysis of Resource Competitiveness and Homelessness Among Young Adults

Homelessness occurs when individual resources are not enough for the demands of a given environment. Exploring homelessness as a process of resource loss on a continuum of poverty leads to research and explanations concerning how people transition from being housed to being homeless. This study assessed the influence of age, gender, and race along with a set of eleven resource competitiveness variables on the risk of youth becoming homeless. Resource competitiveness variables were: parental income, personal income, possession of a driver\u27s license (DL), live-in partner, parenthood, education and training, annual weeks-employed, substance abuse, and incarceration history. The data came from the Bureau of Labor Statistics\u27 National Longitudinal Survey of Youth 1997 (NLSY97). This sample was restricted to those that were homeless or unstably housed and were between the ages of 18 and 24 (n = 141). Each case was then matched by age, gender, and race to two individuals randomly selected from the remaining NLSY97 sample (n = 282). This resulted in an overall N of 423. A growth model was used to analyze the data longitudinally. Partnership, education and training, DL, annual weeks-employed, and personal income were significantly associated with experiences of homelessness and unstable housing. All were negatively related, except for age, which was positively related to incidents of homelessness and unstable housing. Comparisons across the homeless, unstably housed, and control samples showed incremental changes in nearly all the covariates in this study, in relation to changes in housing status, supporting the importance of studying homelessness as a point on a continuum of resource loss versus a discrete state of being

Earthquake Petrology: Linking Fault-Related Deformation to the Earthquake Cycle

Faults have a controlling influence on a variety of geologic processes includingfluid flow, the mechanical behavior of the crust, and seismicity. The geologic sciences have long recognized that faults generate earthquakes; however, few indicators of ancient earthquakes exist in fault-zones. This dissertation documents several indicators for the preservation of ancient earthquakes in fault-zones including frictional melt (pseudotachylyte), highly-polished fault slip surfaces, and hydrothermal alteration. These deformation products result from rapid generation of frictional heat during earthquakes.This dissertation also focuses on the seismic potential of continental low-angle normal faults (LANF). We document the preservation of voluminous pseudotachylyte along a LANF suggesting that the fault repeatedly nucleated large earthquakes. Additionally, a synthesis of reported occurrences of LANF pseudotachylyte indicates that LANF seismicity is common during extension. This has important implication for the mechanics and evolution of LANFs and for the assessment of seismic hazards.We also present a little used, high resolution, and low-cost 3D range camera for use in geolgy. The KinectTM is a 3D infrared range camera that can be used to collect high- resolution (± 1 mm), 3D data in both field and laboratory settings. We describe the use of the KinectTM in geologic appications and recommend more widespread use

Estimating State and Local Tax Exporting Between 1999 and 2012

In fiscal year 2012, state and local governments collected $1.4 trillion in taxes. Using various data sources, this paper presents state-by-state estimates of the amount that each state is able to export of its tax burden to non-residents, including the export effects of federal deductibility. Overall, based on the economic incidence assumptions outlined in this paper, between 12.5 percent and 45 percent of state and local tax collections were ultimately borne by out-of-state residents in FY 2012. This large range is the result of the uncertainty pertaining to the economic incidence of the property tax

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

Evaluating the Role of Income in National Software Piracy

Our study investigates the proper role of income in predicting national software piracy rates. We run regressions isolating various measures of income, including GDP per capita and median household income and variations thereof, to predict national software piracy rates. Then we also run multivariate regressions incorporating GDP and other non-income predictors such as corruption in a manner consistent with previous studies. This topic is of importance due to the multi-billion dollar losses incurred globally each year due to pirating. Our results show that a square root version of median household income is the best measure of national income and consistent with what economic theory predicts.