Triple-peptide receptor targeting in vitro allows detection of all tested gut and bronchial NETs.

UNLABELLED A high proportion of gut and bronchial neuroendocrine tumors (NETs) overexpresses somatostatin receptors, especially the sst2 subtype. It has also recently been observed that incretin receptors, namely glucagonlike peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptors, can be overexpressed in gut and bronchial NETs. However, because not all tumors can express these receptors in sufficient amounts, in vivo imaging with a single radioligand may not always be successful. We therefore evaluated with in vitro methods whether a cocktail of radioligands targeting these 3 receptors would improve tumor labeling. METHODS In vitro receptor autoradiography was performed on 55 NETs, comparing in each successive section of tumor the binding with a single radioligand, either (125)I-Tyr(3)-octreotide, (125)I-GLP-1(7-36)amide, or (125)I-GIP(1-30), with the binding using a cocktail of all 3 radioligands, given concomitantly under identical experimental conditions. RESULTS Using the cocktail of radioligands, all tumors without exception showed moderate to very high binding, with a receptor density corresponding to 1,000-10,000 dpm/mg of tissue; conversely, single-ligand binding, although identifying most tumors as receptor-positive, failed to detect receptors or measured only a low density of receptors below 1,000 dpm/mg in a significant number of tumors. In addition, the cocktail of radioligands always provided a homogeneous labeling of the whole tumor, whereas single radioligands occasionally showed heterogeneous labeling. CONCLUSION The study suggests that the use of a cocktail of 3 radioligands binding to somatostatin receptors, GLP-1 receptors, and GIP receptors would allow detecting virtually all NETs and labeling them homogeneously in vivo, representing a significant improvement for imaging and therapy in NETs.

Achievements and Prospects of Tef Improvement - Proceedings of the Second International Workshop, November 7-9, 2011, Debre Zeit, Ethiopia

These proceedings on ‘Achievements and Prospects of tef Improvement’ is the outcome of the Second International Tef Workshop held at Debre Zeit (Ethiopia), the location which represents the major tef growing areas in the country as well as the oldest and biggest center on tef research. As an indigenous crop, the bulk of tef research is carried out in the country by scientists based at various higher-learning and research institutions. Hence, unlike major crops of the world such as wheat and rice, research on tef benefited little from modern improvement techniques. However, in the recent years, there is an increasing interest by several researchers and funding organizations in developed nations to promote tef research and development through implementation of modern genetic and genomic tools. The recent efforts and progresses made on tef research and development were presented and discussed in detail at the workshop. The tef research and development in Ethiopia has recently shown tremendous improvement. This is witnessed by the decision of the Ethiopian government to award a Gold Medal in November 2012 to our Institute for the discovery and promotion of a very popular Quncho variety. At this juncture, I would like to congratulate all involved in research and development of tef as the achievement was obtained due to concerted efforts of the tef community. The editors of the proceedings did a wonderful job of undertaking the painstaking task of editing all 23 manuscripts presented at the workshop. In addition, the proceedings include a 44-point roadmap for future tef research and development which can be used as a guideline for researchers, development workers and policy makers. I would like to extend my thanks to sponsors of the workshop and the publication of the proceedings.

Analysis of hand kinematics reveals inter-individual differences in intertemporal decision dynamics

During intertemporal decisions, the preference for smaller, sooner reward over larger-delayed rewards (temporal discounting, TD) exhibits substantial inter-subject variability; however, it is currently unclear what are the mechanisms underlying this apparently idiosyncratic behavior. To answer this question, here we recorded and analyzed mouse movement kinematics during intertemporal choices in a large sample of participants (N = 86). Results revealed a specific pattern of decision dynamics associated with the selection of “immediate” versus “delayed” response alternatives, which well discriminated between a “discounter” versus a “farsighted” behavior—thus representing a reliable behavioral marker of TD preferences. By fitting the Drift Diffusion Model to the data, we showed that differences between discounter and farsighted subjects could be explained in terms of different model parameterizations, corresponding to the use of different choice mechanisms in the two groups. While farsighted subjects were biased toward the “delayed” option, discounter subjects were not correspondingly biased toward the “immediate” option. Rather, as shown by the dynamics of evidence accumulation over time, their behavior was characterized by high choice uncertainty.

Decision Support Models for Composing and Navigating through e-Learning Objects

Libraries of learning objects may serve as basis for deriving course offerings that are customized to the needs of different learning communities or even individuals. Several ways of organizing this course composition process are discussed. Course composition needs a clear understanding of the dependencies between the learning objects. Therefore we discuss the metadata for object relationships proposed in different standardization projects and especially those suggested in the Dublin Core Metadata Initiative. Based on these metadata we construct adjacency matrices and graphs. We show how Gozinto-type computations can be used to determine direct and indirect prerequisites for certain learning objects. The metadata may also be used to define integer programming models which can be applied to support the instructor in formulating his specifications for selecting objects or which allow a computer agent to automatically select learning objects. Such decision models could also be helpful for a learner navigating through a library of learning objects. We also sketch a graph-based procedure for manual or automatic sequencing of the learning objects.

Concise Asymmetric Synthesis and Pharmacological Characterization of All Stereoisomers of Glutamate Transporter Inhibitor TFB-TBOA and Synthesis of EAAT Photoaffinity Probes

Glutamate is the major excitatory neurotransmitter in the mammalian brain. Its rapid clearance after the release into the synaptic cleft is vital in order to avoid toxic effects and is ensured by several transmembrane transport proteins, so-called excitatory amino acid transporters (EAATs). Impairment of glutamate removal has been linked to several neurodegenerative diseases and EAATs have therefore received increased attention as therapeutic targets. O-benzylated L-threo-β-hydroxyaspartate derivatives have been developed previously as highly potent inhibitors of EAATs with TFB-TBOA ((2S,3S)-2-amino-3-((3-(4-(trifluoromethyl)benzamido)benzyl)oxy)succinic acid) standing out as low-nanomolar inhibitor. We report the stereoselective synthesis of all four stereoisomers of TFB-TBOA in less than a fifth of synthetic steps than the published route. For the first time, the inhibitory activity and isoform selectivity of these TFB-TBOA enantio- and diastereomers were assessed on human glutamate transporters EAAT1-3. Furthermore, we synthesized potent photoaffinity probes based on TFB-TBOA using our novel synthetic strategy.

Zonal playfield attributes – A stochastic approach to subjective passing affordances in football

Introduction: According to the ecological view, coordination establishes byvirtueof social context. Affordances thought of as situational opportunities to interact are assumed to represent the guiding principles underlying decisions involved in interpersonal coordination. It’s generally agreed that affordances are not an objective part of the (social) environment but that they depend on the constructive perception of involved subjects. Theory and empirical data hold that cognitive operations enabling domain-specific efficacy beliefs are involved in the perception of affordances. The aim of the present study was to test the effects of these cognitive concepts in the subjective construction of local affordances and their influence on decision making in football. Methods: 71 football players (M = 24.3 years, SD = 3.3, 21 % women) from different divisions participated in the study. Participants were presented scenarios of offensive game situations. They were asked to take the perspective of the person on the ball and to indicate where they would pass the ball from within each situation. The participants stated their decisions in two conditions with different game score (1:0 vs. 0:1). The playing fields of all scenarios were then divided into ten zones. For each zone, participants were asked to rate their confidence in being able to pass the ball there (self-efficacy), the likelihood of the group staying in ball possession if the ball were passed into the zone (group-efficacy I), the likelihood of the ball being covered safely by a team member (pass control / group-efficacy II), and whether a pass would establish a better initial position to attack the opponents’ goal (offensive convenience). Answers were reported on visual analog scales ranging from 1 to 10. Data were analyzed specifying general linear models for binomially distributed data (Mplus). Maximum likelihood with non-normality robust standard errors was chosen to estimate parameters. Results: Analyses showed that zone- and domain-specific efficacy beliefs significantly affected passing decisions. Because of collinearity with self-efficacy and group-efficacy I, group-efficacy II was excluded from the models to ease interpretation of the results. Generally, zones with high values in the subjective ratings had a higher probability to be chosen as passing destination (βself-efficacy = 0.133, p < .001, OR = 1.142; βgroup-efficacy I = 0.128, p < .001, OR = 1.137; βoffensive convenience = 0.057, p < .01, OR = 1.059). There were, however, characteristic differences in the two score conditions. While group-efficacy I was the only significant predictor in condition 1 (βgroup-efficacy I = 0.379, p < .001), only self-efficacy and offensive convenience contributed to passing decisions in condition 2 (βself-efficacy = 0.135, p < .01; βoffensive convenience = 0.120, p < .001). Discussion: The results indicate that subjectively distinct attributes projected to playfield zones affect passing decisions. The study proposes a probabilistic alternative to Lewin’s (1951) hodological and deterministic field theory and enables insight into how dimensions of the psychological landscape afford passing behavior. Being part of a team, this psychological landscape is not only constituted by probabilities that refer to the potential and consequences of individual behavior, but also to that of the group system of which individuals are part of. Hence, in regulating action decisions in group settings, informers are extended to aspects referring to the group-level. References: Lewin, K. (1951). In D. Cartwright (Ed.), Field theory in social sciences: Selected theoretical papers by Kurt Lewin. New York: Harper & Brothers.

Anticipatory and reactive forms of blame avoidance: of foxes and lions

Blame avoidance behavior (BAB) encompasses all kinds of integrity-protecting activities by officeholders in the face of potentially blame-attracting events. Although considered essential for a realistic understanding of politics and policymaking, a general understanding of this multi-faceted behavioral phenomenon and its implications has been lacking to date. We argue that this is due to the lack of careful conceptualization of various forms of BAB. Crucially, the difference between anticipatory and reactive forms of BAB is largely neglected in the literature. This paper links anticipatory and reactive forms of BAB as two consecutive decision situations. It exposes dependence relationships between the situations that trigger BAB, the rationalities at work, the resources and strategies applied by blame-avoiding actors, and the various consequences thereof. The paper concludes that anticipatory and reactive BAB are distinct phenomena that require specific research approaches to assess their relevance for the workings of polities.

Coalition Formation in Parliament and during the Policy Process

In modern democratic systems, usually no single collective actor is able to decisively influence political decision-making. Instead, actors with similar preferences form coalitions in order to gain more influence in the policy process. In the Swiss political system in particular, institutional veto points and the consensual culture of policy-making provide strong incentives for actors to form large coalitions. Coalitions are thus especially important in political decision-making in Switzerland, and are accordingly a central focus of this book. According to one of our core claims - to understand the actual functioning of Swiss consensus democracy - one needs to extend the analysis beyond formal institutions to also include informal procedures and practices. Coalitions of actors play a crucial role in this respect. They are a cornerstone of decision-making structures, and they inform us about patterns of conflict, collaboration and power among actors. Looking at coalitions is all the more interesting in the Swiss political system, since the coalition structure is supposed to vary across policy processes. Given the absence of a fixed government coalition, actors need to form new coalitions in each policy process.

'Going Public': The Mediatization of Decision-Making Processes

In most Western countries, the media are said to exert an increasing influence on the political game. This development, which has been described variably as a shift towards an 'audience democracy' (Manin 1995) or the 'mediatization of politics' (Mazzoleni and Schulz 1999), emphasizes the increasing importance of the media for political actors and political decision-making. In such a context, political actors need to communicate with both the media and the public in order to gain support for their policy plans and to influence decision-making. The media were noticeably absent from Kriesi's (1980) in-depth analysis of political decision-making in Switzerland. This suggests that in the early 1970s, the media did not matter or mattered far less than they do today.

Political Decision-Making in Switzerland. The Consensus Model under Pressure

This in-depth study of the decision-making processes of the early 2000s shows that the Swiss consensus democracy has changed considerably. Power relations have transformed, conflict has increased, coalitions have become more unstable and outputs less predictable. Yet these challenges to consensus politics provide opportunities for innovation.