Catechol-binding serines of beta(2)-adrenergic receptors control the equilibrium between active and inactive receptor states.

The binding free energy for the interaction between serines 204 and 207 of the fifth transmembrane helix of the beta(2)-adrenergic receptor (beta(2)-AR) and catecholic hydroxyl (OH) groups of adrenergic agonists was analyzed using double mutant cycles. Binding affinities for catecholic and noncatecholic agonists were measured in wild-type and mutant receptors, carrying alanine replacement of the two serines (S204A, S207A beta(2)-AR), a constitutive activating mutation, or both. The free energy coupling between the losses of binding energy attributable to OH deletion from the ligand and from the receptor indicates a strong interaction (nonadditivity) as expected for a direct binding between the two sets of groups. However, we also measured a significant interaction between the deletion of OH groups from the receptor and the constitutive activating mutation. This suggests that a fraction of the decrease in agonist affinity caused by serine mutagenesis may involve a shift in the conformational equilibrium of the receptor toward the inactive state. Direct measurements using a transient transfection assay confirm this prediction. The constitutive activity of the (S204A, S207A) beta(2)-AR mutant is 50 to 60% lower than that of the wild-type beta(2)-AR. We conclude that S204 and S207 do not only provide a docking site for the agonist, but also control the equilibrium of the receptor between active (R*) and inactive (R) forms.

Financial reforms and capital flows: Insights from general equilibrium

As a result of debt enforcement problems, many high-productivity firms in emergingeconomies are unable to pledge enough future profits to their creditors and this constrains thefinancing they can raise. Many have argued that, by relaxing these credit constraints, reformsthat strengthen enforcement institutions would increase capital flows to emerging economies. Thisargument is based on a partial equilibrium intuition though, which does not take into account theorigin of any additional resources that flow to high-productivity firms after the reforms. We showthat some of these resources do not come from abroad, but instead from domestic low-productivityfirms that are driven out of business as a result of the reforms. Indeed, the resources released bythese low-productivity firms could exceed those absorbed by high-productivity ones so that capitalflows to emerging economies might actually decrease following successful reforms. This resultprovides a new perspective on some recent patterns of capital flows in industrial and emergingeconomies.

Uncertainty, electoral incentives and political myopia

We study the determinants of political myopia in a rational model of electoral accountability where the key elements are informational frictions and uncertainty. We build aframework where political ability is ex-ante unknown and policy choices are not perfectlyobservable. On the one hand, elections improve accountability and allow to keep well-performing incumbents. On the other, politicians invest too little in costly policies withfuture returns in an attempt to signal high ability and increase their reelection probability.Contrary to the conventional wisdom, uncertainty reduces political myopia and may, undersome conditions, increase social welfare. We use the model to study how political rewardscan be set so as to maximise social welfare and the desirability of imposing a one-term limitto governments. The predictions of our theory are consistent with a number of stylised factsand with a new empirical observation documented in this paper: aggregate uncertainty, measured by economic volatility, is associated to better fiscal discipline in a panel of 20 OECDcountries.

Good practice for dialogue and communication as strategic principle for policing political manifestations in Europe (GODIAC):field study handbook

This handbook describes the peer review methodology that was applied at the GODIAC project fi eld studies1. The peer review evaluation method as initiated by Otto Adang in the Netherlands and further developed in a European football context (Adang & Brown, 2008) involves experienced police offi cers cooperating with researchers to perform observational fi eld studies to identify good practices and learning points for public order management. The handbook builds on the GODIAC seminars and workshops, for the fi eld study members, which took place in September 2010, January 2012 and January 2013. The handbook has been discussed in the project group and in the steering committee. It is primarily written for the GODIAC fi eld study members as background material for understanding the fi eld study process and for clarifying the different responsibilities that enable active participation in the fi eld study. The handbook has been developed during the project period and incorporates learning points and developments of the peer review method. The handbook aims at promoting the use of fi eld studies for evaluation of policing major events.

Good practice for dialogue and communication as strategic principle for policing political manifestations in Europe (GODIAC):the anthology

The volume is divided into two parts; the fi rst deals with issues related to the police, and the second addresses issues related to demonstrators and protesters. We hope that this volume will provide further insight into issues associated with policing at major events and shed light on the complexity of the organisations, motives, and strategies in play whenever protester groups are involved.

Good practice for dialogue and communication as strategic principle for policing political manifestations in Europe (GODIAC):recommendations for policing political manifestations in Europe

This report summarises the fi eld study results of the project ’Good practice for dialogue and communication as strategic principles for policing political manifestations in Europe’ (GODIAC).1 The overall idea was to integrate operative police work, research and training within the fi eld and to build international and institutional networks, ensuring and recognising the responsibilities of the organisers. The purpose of the GODIAC project was to contribute to the development of a European approach to policing political manifestations.

Kinship, ritual kinship and political milieus in an alpine Valley in 19th century

In my paper I will present some results about ritual kinship and political mobilization of popular groups in an alpine Valley: the Val de Bagnes, in the Swiss canton of Valais. There are two major reasons to choose the Val de Bagnes for our inquiry about social networks: the existence of sharp political and social conflicts during the 18th and the 19th century and the availability of almost systematic genealogical data between 1700 and 1900. The starting point of my research focuses on this question: what role did kinship and ritual kinship play in the political mobilization of popular groups and in the organization of competing factions? This question allows us to shed light on some other uses and meanings of ritual kinship in the local society. Was ritual kinship a significant instrument for economic cooperation? Or was it a channel for patronage or for privileged social contacts? The analysis highlights the importance of kinship and godparentage for the building of homogeneous social and political networks. If we consider transactions between individuals, the analysis of 19th century Val de Bagnes gives the impression of quite open networks. Men and women tried to diversify their relations in order to avoid strong dependency from powerful patrons. Nevertheless, when we consider the family networks, we can notice that most relations took place in a structured social space or a specific "milieu", were intense contacts enhanced trust, although political allegiances and social choices were not fully predictable on the basis of such preferential patterns. In a politically conflictual society, like 19th century Bagnes, ritual kinship interacted with kinship solidarities and ideological factors shaping dense social networks mostly based on a common political orientation. Such milieus sustained the building of political factions, which show surprising stability over time. In this sense, milieus are important factors to understand political and religious polarization in 19th century Switzerland.