Toward a mechanism for GroEL.GroES chaperone activity: an ATPase-gated and -pulsed folding and annealing cage.

Free GroEL binds denatured proteins very tightly: it retards the folding of barnase 400-fold and catalyzes unfolding fluctuations in native barnase and its folding intermediate. GroEL undergoes an allosteric transition from its tight-binding T-state to a weaker binding R-state on the cooperative binding of nucleotides (ATP/ADP) and GroES. The preformed GroEL.GroES.nucleotide complex retards the folding of barnase by only a factor of 4, and the folding rate is much higher than the ATPase activity that releases GroES from the complex. Binding of GroES and nucleotides to a preformed GroEL.denatured-barnase complex forms an intermediately fast-folding complex. We propose the following mechanism for the molecular chaperone. Denatured proteins bind to the resting GroEL.GroES.nucleotide complex. Fast-folding proteins are ejected as native structures before ATP hydrolysis. Slow-folding proteins enter chaperoning cycles of annealing and folding after the initial ATP hydrolysis. This step causes transient release of GroES and formation of the GroEL.denatured-protein complexes with higher annealing potential. The intermediately fast-folding complex is formed on subsequent rebinding of GroES. The ATPase activity of GroEL.GroES is thus the gatekeeper that selects for initial entry of slow-folding proteins to the chaperone action and then pumps successive transitions from the faster-folding R-states to the tighter-binding/stronger annealing T-states. The molecular chaperone acts as a combination of folding cage and an annealing machine.

Front elevation and floor plans for first and second floors, ink and wash on paper, [ca. 1812]

Drawing by Charles Bulfinch of proposed plans for University Hall which were later rejected. Includes sketches of the front exterior view of the University Hall, and separate floor plans for the ground and second floors. Bulfinch designed a ground floor with a chapel and four dining halls each holding 100 students, a second floor with a gallery in the chapel and three rooms over the dining halls for public examinations and meetings of the Corporation and Overseers; and a basement under the halls intended for a kitchen under the dining halls and recitation rooms under the chapel.

Überlegungen zu Ressourceneffizienz und Recycling = Reflections on resource efficiency and recycling. Research Paper in Law 6/2003

No abstract.

De Gaulle and Europe: Historical Revision and Social Science Theory. Program for the Study of Germany and Europe Working Paper Series 8.5

The thousands of books and articles on Charles de Gaulle's policy toward European integration, whether written by historians, social scientists, or commentators, universally accord primary explanatory importance to the General's distinctive geopolitical ideology. In explaining his motivations, only secondary significance, if any at all, is attached to commercial considerations. This paper seeks to reverse this historiographical consensus by examining the four major decisions toward European integration during de Gaulle's presidency: the decisions to remain in the Common Market in 1958, to propose the Foucher Plan in the early 1960s, to veto British accession to the EC, and to provoke the "empty chair" crisis in 1965-1966, resulting in the "Luxembourg Compromise." In each case, the overwhelming bulk of the primary evidence-speeches, memoirs, or government documents-suggests that de Gaulle's primary motivation was economic, not geopolitical or ideological. Like his predecessors and successors, de Gaulle sought to promote French industry and agriculture by establishing protected markets for their export products. This empirical finding has three broader implications: (1) For those interesred in the European Union, it suggests that regional integration has been driven primarily by economic, not geopolitical considerations--even in the "least likely" case. (2) For those interested in the role of ideas in foreign policy, it suggests that strong interest groups in a democracy limit the impact of a leader's geopolitical ideology--even where the executive has very broad institutional autonomy. De Gaulle was a democratic statesman first and an ideological visionary second. (3) For those who employ qualitative case-study methods, it suggests that even a broad, representative sample of secondary sources does not create a firm basis for causal inference. For political scientists, as for historians, there is in many cases no reliable alternative to primary-source research.

Russia and the Common Space on Freedom, Security and Justice. CEPS Paper on Liberty and Security in Europe No. 54, 25 February 2013

EU-Russia cooperation in the framework of the Common Space on Freedom, Security and Justice, launched almost a decade ago in 2003, has borne fruit more in the security aspects than the justice and liberty-related policy areas. This study assesses the uneven cooperation on justice and home affairs between the EU and Russia, while delving into the intersection between cooperation on justice, liberty and security and the promotion of human rights, democracy and rule of law in EU-Russia relations. The study concludes by proposing a set of policy recommendations to the European Parliament for playing a more active role in this important field of cooperation between the EU and Russia.

The ‘Lisbonisation’ of the European Parliament: Assessing progress, shortcomings and challenges for democratic accountability in the area of freedom, security and justice. CEPS Paper on Liberty and Security in Europe No. 58, September 2013

This paper examines the performance of the European Parliament in EU AFSJ law and policy-making from the entry into force of the Lisbon Treaty until the end of the first half of 2013. The paper situates the EP in the new post-Lisbon institutional setting, documenting its transition to ‘AFSJ decision-maker’, and its new powers to shape and make policy covering the EU’s internal and external security agenda. While the paper finds that the EP has become an active co-owner of the EU AFSJ post-Lisbon, with the Parliament demonstrating a dynamic adjustment to its new post-Lisbon role and powers, the authors identify a set of new developments and challenges that have arisen in the conduct of democratic accountability by the EP in the AFSJ since 2009, which call for critical reflection ahead of the new parliamentary term 2014-2019 and the post-2014 phase of the EU’s AFSJ.