The activating role of phospho-(Tyr)-calmodulin on the epidermal growth factor receptor

The activity of calmodulin (CaM) is modulated not only by oscillations in the cytosolic concentration of free Ca2+, but also by its phosphorylation status. In the present study, the role of tyrosine-phosphorylated CaM [P-(Tyr)-CaM] on the regulation of the epidermal growth factor receptor (EGFR) has been examined using in vitro assay systems. We show that phosphorylation of CaM by rat liver solubilized EGFR leads to a dramatic increase in the subsequent phosphorylation of poly-L-(Glu:Tyr) (PGT) by the receptor in the presence of ligand, both in the absence and in the presence of Ca2+. This occurred in contrast with assays where P-(Tyr)-CaM accumulation was prevented by the presence of Ca2+, absence of a basic cofactor required for CaM phosphorylation and/or absence of CaM itself. Moreover, an antibody against CaM, which inhibits its phosphorylation, prevented the extra ligand-dependent EGFR activation. Addition of purified P-(Tyr)-CaM, phosphorylated by recombinant c-Src (cellular sarcoma kinase) and free of non-phosphorylated CaM, obtained by affinity-chromatography using an immobilized anti-phospho-(Tyr)-antibody, also increased the ligand-dependent tyrosine kinase activity of the isolated EGFR toward PGT. Also a CaM(Y99D/Y138D) mutant mimicked the effect of P-(Tyr)-CaM on ligand-dependent EGFR activation. Finally, we demonstrate that P-(Tyr)-CaM binds to the same site (645R-R-R-H-I-V-R-K-R-T-L-R-R-L-L-Q660) as non-phosphorylated CaM, located at the cytosolic juxtamembrane region of the EGFR. These results show that P-(Tyr)-CaM is an activator of the EGFR and suggest that it could contribute to the CaM-mediated ligand-dependent activation of the receptor that we previously reported in living cells.

Derivation of the spin Hamiltonians for Fe in MgO

A method to calculate the effective spin Hamiltonian for a transition metal impurity in a non-magnetic insulating host is presented and applied to the paradigmatic case of Fe in MgO. In the first step we calculate the electronic structure employing standard density functional theory (DFT), based on generalized gradient approximation (GGA), using plane waves as a basis set. The corresponding basis of atomic-like maximally localized Wannier functions is derived and used to represent the DFT Hamiltonian, resulting in a tight-binding model for the atomic orbitals of the magnetic impurity. The third step is to solve, by exact numerical diagonalization, the N electron problem in the open shell of the magnetic atom, including both effects of spin–orbit and Coulomb repulsion. Finally, the low energy sector of this multi-electron Hamiltonian is mapped into effective spin models that, in addition to the spin matrices S, can also include the orbital angular momentum L when appropriate. We successfully apply the method to Fe in MgO, considering both the undistorted and Jahn–Teller (JT) distorted cases. Implications for the influence of Fe impurities on the performance of magnetic tunnel junctions based on MgO are discussed.

How buildings visualise client and architect: The problem that today’s user is typically not the client

An article presented at the last ICAT- conference stated at the end that buildings at all times tend to picture the people who had them erected. This paper aims to show the correctness of that statement. To this end, it will examine a number of typical residential buildings dating from the beginning of the seventeenth century up to today, investigate who had the buildings erected, and relate that to the performance of the buildings. This relation analysis will mainly use the scale but also the degree of diversity in function and appearance as factors. Furthermore, using economic data and data on the buildings to identify patterns, it will investigate how size of the property and relative size of the capital interest behind the building has developed. Since the authors live in Copenhagen and Copenhagen is very typical in its historical development, buildings and environments in and around the centre of Copenhagen are used as examples.

An Architecture by means of Anthropology. Beyond learning the tools of social science

Los arquitectos y urbanistas tienen una larga tradición en el aprendizaje de las herramientas de las ciencias sociales, especialmente las que les permiten analizar y describir mejor los entornos y las personas para las que trabajan. Esto ha llevado a los arquitectos a desarrollar mejores herramientas de observación y descripción del ámbito social y no sólo el material. Sin embargo, la mayoría de las veces este acercamiento interdisciplinar ha identificado las ciencias sociales, especialmente la antropología, con la etnografía. Este artículo parte de la crítica a esta identificación hecha por el antropólogo Tim Ingold y se centra en lo que él propone como el método central de la antropología, la observación participante. Para después revisar varias propuestas actuales de científicos sociales que tratan de desarrollar una disciplina no representacional y orientada al futuro, un objetivo más cercano al de la arquitectura. El artículo intenta imaginar cómo esta práctica transdisciplinar podría desarrollarse.

Members of the General Court, 1798-1799

Notebook with paper cover containing a handwritten list of the members of the Massachusetts General Court arranged by county and town. Pearson identified characteristics of the politicians including whether they were chosen by the people or Legislature, were for or against the College, were for or against the Virginia Resolutions, and whether they were "a good Federalist."

The future of the Eurozone and the role of the German Constitutional Court. Research Papers in Law, 05/2012

[Introduction.] Necessary reforms towards a deepened and increased European shaped economic, financial and budgetary policy, paraphrased with the term “fiscal union”, could possibly reach constitutional limits. In its EFSF judgment1, the German Constitutional Court, following the Lisbon judgment in which certain government tasks were determined as being part of the “constitutional identity”2, connected the budget right of the parliament via the principle of democracy to the eternity clause of Art. 79 para 3 Basic Law. A transfer of essential parts of the budget right of the German Bundestag, which would be in conflict with the German constitution, is said to exist when the determination of the nature and amount of the tax affecting the citizens is largely regulated on the supranational level and thereby deprived of the Bundestag’s right to disposition. A reform of the Economic and Monetary Union that touches the core of the budget right can, according to the German Federal Court, with regard to Art. 79 (3) of the Basic Law only be realized by way of Art. 146 of the Basic Law, thus with a new constitution given by the people that replaces the Basic Law.3

"Viewers should not try this at home". Die Verfassungsgerichte Bosnien-Herzegowinas und Kosovos in deren Rolle als Schlichtungsinstanzen in ethnopolitischen Konflikten = The constitutional courts of Bosnia-Herzegovina and Kosovo in their role as arbitration bodies in ethno-political conflicts. EDAP 01/2014

The article analyzes the role of constitutional courts in Bosnia and Kosovo, both characterized by their partly internationalized membership, in the adjudication of cases that are highly controversial between the different ethno-political factions. The main focus is on the Constitutional Court of Bosnia, which presents one of the richest and most interesting examples of “lawfare” in divided societies. The concept of lawfare has been adapted to refer to the continuation of political battles by ethno-political actors through legal means, in this case, constitutional adjudication. In Kosovo, the Constitutional Court has been an important defender of diversity, albeit its primary focus and merit are to have contributed to the establishment of a concept of democracy close to the people of Kosovo. The article concludes that constitutional courts represent important institutions of internal conflict resolution in divided societies, which have been instrumental in shaping multiculturalism in these post-conflict societies divided by deep ethnic cleavages.

EU integration and party politics in the Balkans. EPC Issue Paper No.77, September 2014

Throughout the Balkan region, popularly elected leaders consistently fail to meet the democratic standards set by the EU and, more importantly, they fall short of their voters’ expectations. Distrust in representative institutions and disengagement from political life runs dramatically high among the people of the Balkan countries, and this generalised sense of dissatisfaction is starting to breed cynicism also towards the idea of a better future inside the Union. This study highlights the interplay between EU integration and national politics in the region, and that both are consequential for the quality of Balkan democracies, as well as reminiscent of the Western and Central and Eastern European experience.

Could an independent Scotland join the European Union? EPC Policy Brief, 28 May, 2014

The people of Scotland vote on 18 September 2014 in a referendum on the question "Should Scotland be an independent country?" The Scottish Government aims, if the result is 'yes', for Scotland to become independent in March 2016 and to join the main international organisations including the European Union. Would that be possible? How could Scotland join the EU? What is the link between Scotland's referendum on independence and a British referendum on EU membership?

The benefits of Union? EPC Commentary, 19 September 2014

Yesterday, as predicted by the polls, the people of Scotland rejected independence, opting to remain part of the United Kingdom, which also means that the EU does not have to face a Scottish application for membership. Some claim that this referendum has buried the question of Scottish independence indefinitely but this debate is probably not over: a UK referendum on EU membership would reopen the independence question, as Scotland tends to see the EU more favourably.

The 2011 Constitutional reform in Morocco: more flaws than merits. Jean Monnet Occasional Paper No. 07/2014

Introduction. In the speech given to both Houses of Parliament on 11 October 2013 during the first parliamentary session, King Mohammed VI said that the “Moroccan democratic model” was “a precursor in the region as well as on the continental level.”1 Similarly, with the purpose of stressing the “democratic exceptionalism”2 of the country, the new government, led by Abdeilah Benkirane, emphasised that Morocco represents a “third way” compared to countries such as Tunisia, Libya or Egypt since it “…has not embarked on a limited process of reform from the top, driven and controlled by the King. Nor has it experienced a revolution brought a angry citizens rising up against the regime. Rather, it has chosen an alternate path based on a genuine partnership between the King and the PJD (Parti de la justice et du développement) that promises to bring about more far-reaching reform than palace alone would grant, without the disruption caused by uncontrolled popular upheaval.”4 It should not be at all surprising that the regime and the new Government consider Morocco a “democratic model” or a “third way.” After all, they are refe country. What is harder to understand is that when discussing the Arab uprisings, even prominent Western political leaders, representatives of the European Union institutions and the mainstream media (when they do not forget about Morocc to praise the process of democratic reform carried out by Mohammed VI. For example, on 12 September 2012, Hillary Clinton, former US Secretary of State, said, “in many ways, the United States looks to Morocco to be a leader and a model […] On political reform, we have all seen remarkable changes taking place across North Africa and the Middle East. I commend Morocco and your government for your efforts to stay ahead of these changes by holding free and fair elections, empowering the elected parliament, taking other steps to ensure that the government reflects the will of the people.”5 Similarly, former French President Nicolas Sarkozy sang the praises of the process that led to the adoption of the new 2011 Constitution: “King Mohammed VI has shown the path towards a profound, peaceful and modern transformation of Moroccan institutions and society […] France fully supports this exemplary process.” Interestingly enough, even at the European Union level the constitutional reform that took more far-reaching reform than palace alone would grant, without the disruption caused by uncontrolled popular upheaval.”4 It should not be at all surprising that the regime and the new Government consider Morocco a “democratic model” or a “third way.” After all, they are refe country. What is harder to understand is that when discussing the Arab uprisings, even prominent Western political leaders, representatives of the European Union institutions and the mainstream media (when they do not forget about Morocc to praise the process of democratic reform carried out by Mohammed VI. For example, on 12 September 2012, Hillary Clinton, former US Secretary of State, said, “in many ways, the United States looks to Morocco to be a leader and a model […] On political reform, we have all seen remarkable changes taking place across North Africa and the Middle East. I commend Morocco and your government for your efforts to stay ahead of these changes by holding free and fair elections, empowering the elected parliament, taking other steps to ensure that the government reflects the will of the people.”5 Similarly, former French President Nicolas Sarkozy sang the praises of the process that led to the adoption of the new 2011 Constitution: “King Mohammed VI has shown the path towards a profound, peaceful and modern transformation of Moroccan institutions and society […] France fully supports this exemplary process.” Interestingly enough, even at the European Union level the constitutional reform that took place in Morocco was considered an extremely positive step taken by the country, as well as a means to strengthen the cooperation between the EU and Morocco. Indeed, according to the High Representative Catherine Ashton, this reform “constitute[s] a significant response to the legitimate aspirations of the Moroccan people and [is] consistent with Morocco’s Advanced Status with the EU.”7 When it comes to the media, it is worth noting that following the ratification of the 2011 Constitution, The New York Times headlined: “All Hail the (Democratic) King.” Even sections of the academic literature have commended the constitutional reform carried out by the Moroccan Sovereign.9 In this paper I argue against the aforementioned idea, according to which Morocco should be considered a model in the region, and in particular I show that the constitution-making process, the 2011 Constitution and its subsequent implementation have more flaws than merits. Accordingly, this paper proceeds in five steps. First of all, I examine the reaction of the regime to the upheavals that broke out in the country after 20 February 2011. Secondly, I analyse the process of constitution showing its main strengths and weaknesses, and comparing it with other constituent processes that took place in the region following the Arab uprisings. In the third section, I highlight the most significant elements of continuity and discontinuity with the previous 1996 Constitution. The fourth section deals with the process of implementation: specifically process is proceeding quite slowly and that in some cases ordinary legislation is in contrast with the new Constitution and international human rights treaties. Moreover, I discuss the role that the judiciary and the Constitutional Court can play in the implementation and interpretation of the Constitution. Finally, I draw some concluding remarks.

The growth challenge for Europe and the EMU. CHALLENGE EUROPE Issue 22- Challenges and new beginnings: Priorities for the EU's new leadership, September 2014.

The European economy is slowly and painfully striving to reemerge from the last six years of crisis. It was a crisis of enormous intensity and contagiousness, given the unprecedented depth of global financial integration combined with the systemic flaws in the EMU architecture. And it is not over, as the high levels of unemployment and the growing divergence between Member States testify. The threat of fragmentation is imminent as ever: fragmentation between euro-ins and euro-outs; fragmentation between North and South; fragmentation within societies, with increasing income inequality and a growing number of, what used to be, the middle class population slipping through the social safety net and below poverty lines. Policies of front-loaded fiscal consolidation have left welfare states in economically weaker countries severely underfunded. According to OECD data, the number of people living in households without any income from work has doubled in Greece, Ireland and Spain, and has risen by 20% or more in Estonia, Italy, Latvia, Portugal, and Slovenia. Fertility rates have dropped further since the crisis, deepening the demographic and fiscal challenges of ageing. There are long-term implications from these deteriorating trends, regarding people's long-term health, education and upward mobility from low-income families. It is also highly likely that many of the people unemployed for a long period of time will never again be able to gain proper access to the job market and build a normal career track. The enduring effects of the crisis risk creating vicious cycles of low growth, high debt levels, austerity, declining productivity, and stagnation. These developments carry heavy implications for the future growth prospects of the European economies, for future prosperity, and for the sustainability of pension systems and welfare states. They must be urgently reversed.

Proportionality needed in the subsidiarity debate in the EU – Appraisal of the British and Dutch initiatives. CEPS Essay No. 11, 8 April 2014

In a new CEPS Essay, Michael Emerson assesses the initiatives taken by the UK and Dutch governments to cut out excessive EU regulatory intrusion, namely in the form of the ongoing British Balance of Competences Review and the Dutch list of 54 items of EU regulation that they would like to see repealed or reformed. He concludes that while one can approve of a campaign for better EU regulation and for cutting out unnecessary micro-regulation, it would require impressive commitment by all member states and the EU institutions to follow the best features of the British and Dutch leads for this to have a real effect in the fight against populist euroscepticism. In his view, that battle will have to be won primarily with bigger weapons – some combination of better macroeconomic results, bigger foreign policy achievements and the emergence of a European-level political leadership to which the people can relate. In short, there has to be due proportionality in the diagnosis of the responsibility of inadequate subsidiarity for the EU’s ills.

Oligarchs after the Maidan: the old system in a 'new' Ukraine. OSW Commentary No. 162, 2015-02-16

From the Introduction. There have been major changes in the balance of forces among the key Ukrainian oligarchs, representatives of big business with strong political influence, since the victory of the Maidan revolution. However, these changes have not undermined the oligarchic system per se. Over the past decade or so, the oligarchs have been key players in Ukrainian politics and economy, and they have retained this position until the present. One of the effects of the change of the government in Kyiv and the war in the Donbas was the elimination of the influence of ‘the family’ – the people from Viktor Yanukovych’s inner circle who formed the most expansive oligarchic group in Ukraine at the time of his presidency. The influence of Rinat Akhmetov, the country’s wealthiest man, has also weakened significantly; Akhmetov was one of the most influential people in Ukraine for more than ten years, partly owing to his close bonds with Yanukovych. Dmytro Firtash’s group has also lost a great deal of its influence since Firtash was arrested in Austria in March 2014.

The History and Challenges of Cohesion Policies. Jean Monnet/Robert Schuman Paper Series Vol. 14 No. 2, February 2014

From Introduction. Regional economic disequilibria was viewed as both an obstacle to and result of integration (European Commission 1965; European Commission 1962; European Commission 1969). Even within the Treaty of Rome, the Community tried to establish mechanisms to alleviate regional inequality. However, it was not until 1975 that the main mechanism of regional policy was established as a result of British and Irish enlargement: the European Regional Development Fund (ERDF). Since then, cohesion policy has become a significant EU expenditure accounting for €347bn, or 35.7% of the total EU budget for 2007-13(European Commission Regional Policy-Info Regio 2012). It has also become a key policy linked to enlargement. The underlying principle of cohesion policy assumes that the market alone cannot solve development problems and therefore government intervention is needed. This notion is in direct contrast to the underlying principle of EU competition policy, which asserts that the free market can solve economic development problems (Meadows, interview by author, 2003). The logic underlying cohesion policy is not only counter to EU competition policy, but also regulatory policies. Unlike other EU policies, cohesion policy is not a sectoral policy, but rather territorial in nature (Leonardi, 2006). Thus at times EU regulatory policy has also unintentionally worked counter to the goals of regional policy, sometimes disadvantaging poorer regions (Dudek, 2005). As the Community has sought to ameliorate regional disparities, it meant that all levels of government: local, regional, national and supranational would need to be involved, however, member states have different territorial governance and European regional development programs have to varying degrees impacted the relationship and policy responsibility of different levels of government (Leonardi, 2006; Bachtler and Michie 1993; Marks, 1993). The very nature of regional development policy has provoked a re-examination of subsidiarity, or which level of government is the lowest and most appropriate level. The discussion of policy formulation and implementation at the lowest level possible also addresses the issue of the democratic deficit. Some argue that the closer government is to the people the more responsive and representative it is. Democracy, however, also implies that public funds are used in a transparent way and for public rather than private good. Yet, as we examine the history and current situation of EU regional funds we find that corruption and misuse still abound. Thus, to understand the history of regional policy it is imperative to look at the major transformations of the policy, how regional policy has impacted subsidiarity and the quality of democracy, become an important instrument of enlargement and contradicted or conflicted with other EU policies.