Submillisecond folding of monomeric lambda repressor.

The folding kinetics of a truncated form of the N-terminal domain of phage lambda repressor [lambda 6-85] has been investigated by using the technique of dynamic NMR. lambda 6-85 has been shown previously to fold in a purely two-state fashion. This allows the determination of folding and unfolding rates from simulation of the exchange-broadened aromatic resonances of Tyr-22. The folding kinetics were determined over a range of 1.35 to 3.14 M urea. The urea dependence of both folding and unfolding rate constants is exponential, suggesting that the rate-determining step is invariant at the urea concentrations studied. The folding and unfolding rates extrapolated to 0 M urea at 37 degrees C are 3600 +/- 400 s-1 and 27 +/- 6 s-1, respectively. The observed lambda 6-85 folding rate constant exceeds that of other fast-folding globular proteins by a factor of 14-54. The urea dependence of the folding and unfolding rate constants suggests that the transition state of the rate-determining step is considerably more exposed to solvent than previously studied protein-folding transition states. The surprising rapidity of lambda 6-85 folding and unfolding may be the consequence of its all-helical secondary structure. These kinetic results clearly demonstrate that all of the fundamental events of protein folding can occur on the submillisecond time scale.

Structure and stability of a second molten globule intermediate in the apomyoglobin folding pathway.

Apomyoglobin folding proceeds through a molten globule intermediate (low-salt form; I1) that has been characterized by equilibrium (pH 4) and kinetic (pH 6) folding experiments. Of the eight alpha-helices in myoglobin, three (A, G, and H) are structured in I1, while the rest appear to be unfolded. Here we report on the structure and stability of a second intermediate, the trichloroacetate form of the molten globule intermediate (I2), which is induced either from the acid-unfolded protein or from I1 by > or = 5 mM sodium trichloroacetate. Circular dichroism measurements monitoring urea- and acid-induced unfolding indicate that I2 is more highly structured and more stable than I1. Although I2 exhibits properties closer to those of the native protein, one-dimensional NMR spectra show that it maintains the lack of fixed side-chain structure that is the hallmark of a molten globule. Amide proton exchange and 1H-15N two-dimensional NMR experiments are used to identify the source of the extra helicity observed in I2. The results reveal that the existing A, G, and H helices present in I1 have become more stable in I2 and that a fourth helix--the B helix--has been incorporated into the molten globule. Available evidence is consistent with I2 being an on-pathway intermediate. The data support the view that apomyoglobin folds in a sequential fashion through a single pathway populated by intermediates of increasing structure and stability.

Low concentrations of diacylglycerol promote the binding of apolipophorin III to a phospholipid bilayer: a surface plasmon resonance spectroscopy study.

The binding of the exchangeable apolipoprotein apolipophorin III (apoLp-III) to an egg phosphatidylcholine bilayer as a function of the concentration of diacylglycerol (DG) in the bilayer was studied by surface plasmon resonance spectroscopy. At a DG concentration of 2 mol % in the bilayer, the binding of apoLp-III reached saturation. Under saturating conditions, apoLp-III forms a closely packed monolayer approximately 55 A thick, in which each molecule of protein occupies approximately 500 A2 at the membrane surface. These dimensions are consistent with the molecular size of the apoLp-III molecule determined by x-ray crystallography, if apoLp-III binds to the bilayer with the long axis of the apoLp-III normal to the membrane surface. In the absence of protein, the overall structure of the lipid bilayer was not significantly changed up to 2.5 mol% DG. However, at 4 and 6 mol % DG, the presence of nonbilayer structures was observed. The addition of apoLp-III to a membrane containing 6 mol % DG promoted the formation of large lipid-protein complexes. These data support a two-step sequential binding mechanism for binding of apoLp-III to a lipid surface. The first step is a recognition process, consisting of the adsorption of apoLp-III to a nascent hydrophobic defect in the phospholipid bilayer caused by the presence of DG. This recognition process might depend on the presence of a hydrophobic sensor located at one of the ends of the long axis of the apoLp-III molecule but would be consolidated through H-bond and electrostatic interactions. Once primary binding is achieved, subsequent enlargement of the hydrophobic defect in the lipid surface would trigger the unfolding of the apolipoprotein and binding via the amphipathic alpha-helices. This two-step sequential binding mechanism could be a general mechanism for all exchangeable apolipoproteins. A possible physiological role of the ability of apoLp-III to bind to lipid structures in two orientations is also proposed.

Towards a new multilateral energy architecture? Security Policy Brief No. 39, October 2012

From climate change over peak oil to the geopolitical scramble for the Arctic, there are ample signs that a global energy crisis is unfolding. The sheer scale and urgency of this looming crisis calls for international coordination. Yet, even a cursory look at the existing international energy institutions leads to a sobering conclusion: the global energy governance architecture is weak, fragmented and incomplete. This policy brief discusses both the flaws in the multilateral energy architecture and some emerging ideas to strengthen it, such as the proposal for a Sustainable Energy Trade Agreement and the new American disclosure rules for the extractive sector.

Immigration and free movement in an unusual electoral race: what implications for the next political cycle? EPC Policy Brief, 20 May 2014

Immigration and freedom of movement of EU citizens are among the main issues debated throughout the European Parliament election campaign and have some potential in determining who tomorrow’s EU leaders will be. This Policy Brief looks at how the two policies are debated at national level – in France, Germany and the UK – and at EU level between the ‘top candidates’ for European Commission Presidency – Jean-Claude Juncker (EPP), Ska Keller (Greens), Martin Schulz (PES) and Guy Verhofstadt (ALDE) – who have participated in several public debates. Two different campaigns have been unfolding in front of EU citizens’ eyes. The tense debate that can be identified at national level on these issues, is not transferred to the EU level, where immigration and free movement are less controversial topics. Furthermore, although participating in European elections, national parties present agendas responding exclusively to the economic and social challenges of their Member State, while the candidates for the Commission Presidency bring forward ‘more European’ programmes. Hence, several aspects need to be reflected upon: What will the consequences of this discontinuity be? How will this impact the future European agenda in terms of immigration and free movement? What institutional consequences will there be? Answering these questions is not a simple task, however, this paper aims to identify the parameters that need to be taken into account and the political landscape which will determine the future EU agenda in terms of immigration and free movement.

The tug of war. Russia's response to changes on the European gas market. OSW Study 50/2014

Russia, being aware of the evolution of the EU gas market and the fluctuations in trends that accompany it, and in an attempt to maintain its position on the European gas market, is sticking to a dichotomous strategy. On the one hand, Moscow has taken an offensive approach: it continues its traditionally critical rhetoric with regard to the legal and institutional changes; by negating the legitimacy of the new rules, it has been making efforts to undermine them by employing legal and political measures; Russia has used such traditional economic means as investments in assets and pushing through the implementation of new gas pipeline construction projects. On the other hand, the evolution of the EU gas market has forced Russia to take steps to adapt to a certain extent: partial changes in the operation of the internal gas sector; promises to further curb Gazprom’s dominant position; the concessions made in trade negotiations with European partners; partial adjustments to the EU’s so called third energy package regulations. Hoping that the unfolding situation on the gas markets will contribute to slowing down the recent liberalisation tendencies in the EU and that EU member states won’t make progress in decreasing their dependence on Russian gas, Moscow is thus preparing itself for the ‘long game’ in gas with its European partners.

The eurozone in bad need of a psychiatrist. EuropEos Commentary No. 6, 9 December 2010

Stefano Micossi, Director General of Assonime and member of the CEPS Board of Directors, observes in a new EuropEos Commentary that there is something surreal to the unfolding financial crisis of the eurozone, as the leaders grudgingly do what is needed to prevent disaster just minutes before it’s too late, and then in the next minute revert to the same behaviour that had brought them against the wall in the first place. He cites rising sovereign spreads within the area as the visible result of this strategy: they signal investors’ expectation that the future can only bring more of the same, a series of ever-larger sovereign debt crises, under Damocles’ sword that at some stage Germany, the paymaster of last resort, will close its purse and let Armageddon start.

Synthesis Report on the Impact of Capital Use. Factor Markets Working Document No. 57, August 2013

This paper examines the drivers of productivity in EU agriculture from a factor markets perspective. Using econometrically estimated production elasticities and shadow prices of factors for a set of eight EU member states, we focus on field crop farms represented in the FADN database for the years 2002-08. As it turned out that output reacts most elastically to materials input, we investigate this factor further and find different rationing regimes represented in different member states. Marginal return on materials is low in Denmark and West Germany, but significantly above typical market interest rates in East Germany, Italy and Spain. In the latter countries and in Denmark it also increased towards the end of the observed period. This finding is consistent with a perception of tightening funding access, possibly induced or reinforced by the unfolding financial crisis. Marginal returns to land, labour and fixed capital are generally low. We conclude that the functioning of factor markets plays a crucial role for productivity growth, but that factor market operations display considerable heterogeneity across EU member states.

The Eurasian Economic Union – more political, less economic. OSW Commentary Number 157/20.01.2015

The Eurasian Economic Union is undoubtedly the most comprehensive form of economic integration of the post-Soviet countries since the break-up of the Soviet Union. However, the way in which the integration process has been unfolding, as well as Russia’s aggressive policy over the last year, are indications that the EEU has become primarily a political project, and the importance of its economic aspects has eroded. This has triggered a change in the way Kazakhstan and Belarus treat the EEU. Initially, the two countries viewed integration as an opportunity for the development of genuine economic co-operation. However, Russia’s annexation of Crimea and the conflict in Ukraine have revealed the real significance of the EEU project – as a tool to reinforce Russian influence in the post-Soviet area and isolate the post-Soviet countries from the West and China. While the Kremlin presents the EEU as the Eurasian equivalent of the European Union, the project is in reality an imitation of integration. The reasons for this include the nature of the political systems in the participating countries, which are authoritarian, prone to instrumentalise law, and affected by systemic corruption; the aggressive policy that Russia has been pursuing over the last year; and Russia’s dominant role in defining the shape of the EEU. The EEU appears to be based on forceful integration, and is becoming less and less economically attractive for its member countries other than Russia. Moreover, it is clearly assuming a political dimension that those other member countries perceive as dangerous. For these reasons, its functioning will depend on the power and position of Russia. In the longer term it is likely that the other member states will try to ‘sham’ and delay closer integration within the EEU. This means that if Russia becomes politically and economically weaker, the EEU may evolve into an increasingly dysfunctional organisation – a development that will be reinforced by the low standards of legal culture in its member states and their reluctance to integrate. Should Russia’s power increase, the EEU will become an effective instrument of Russian dominance in the area of the former USSR.

Constructing, Creating and Contesting Cityscapes. A Socio-Anthropological Approach to Urban Transformation in Southern Xinjiang, People’s Republic of China

This manuscript is based on a PhD thesis submitted at the Institute of Social Anthropology at the University of Bern in 2014. The dissertation was part of the research project „Xinjiang Uyghur Autonomous Region and Chinese Territoriality. The Development of Infrastructure and Han Migration into the Region“ under the supervision of Prof. Dr. Heinzpeter Znoj and financed by the Swiss National Science Foundation SNSF. Madlen Kobi analyzes the architectural and socio-political transformation of public places and spaces in rapidly urbanizing southern Xinjiang, P.R. China, and in doing so pays particular attention to the cities of Aksu and Kaxgar. As the Xinjiang Uyghur Autonomous Region lies in between China and Central Asia, it is especially characterized by differing political, cultural, and religious influences, and, furthermore, due to its being a multiethnic region, by multiple identities. One might expect cultural and social identities in this area to be negotiated by referring to history, religion, or food. However, they also become visible by the construction and reconstruction, if not demolition, of public places, architectural landmarks, and private residences. Based on ethnographic fieldwork performed in 2011 and 2012, the study explores everyday life in a continuously transforming urban environment shaped by the interaction of the interests of government institutions, investment companies, the middle class, and migrant workers, among many other actors. Here, urban planning, modernization, and renewal form a highly sensitive lens through which the author inspects the tense dynamics of ethnic, religious, and class-based affiliations. She respects varieties and complexities while thoroughly grounding unfolding transformation processes in everyday lived experiences. The study provides vivid insights into how urban places and spaces in this western border region of China are constructed, created, and eventually contested.

Realizing the Witch : Science, Cinema, and the Mastery of the Invisible /

Realizing the Witch follows the unfolding of Benjamin Christensen’s visual narrative in his 1922 film, Häxan (The Witch). Through a close reading of Häxan, Baxstrom and Meyers examine the study of witchcraft from historical and anthropological perspectives, as well as the intersection of popular culture, artistic expression and scientific ideas. This title was made Open Access by libraries from around the world through Knowledge Unlatched.

Risk Criticism : Precautionary Reading in an Age of Environmental Uncertainty /

'Risk Criticism: Reading in an Age of Manufactured Uncertainties' is a study of literary and cultural responses to global environmental risk that offers an environmental humanities approach to understanding risk in an age of unfolding ecological catastrophe. In 2015, the Bulletin of the Atomic Scientists re-set its iconic Doomsday Clock to three minutes to midnight, as close to the apocalypse as it has been since 1953. What pushed its hands was, however, not just the threat of nuclear weapons, but also other global environmental risks that the Bulletin judged to have risen to the scale of the nuclear, including climate change and innovations in the life sciences. If we may once have believed that the end of days would come in a blaze of nuclear firestorm (or the chill of the subsequent nuclear winter), we now suspect that the apocalypse may be much slower, creeping in as chemical toxin, climate change, or bio- or nano- technologies run amok. Taking inspiration from the questions raised by the Bulletin’s synecdochical “nuclear,” 'Risk Criticism' aims to generate a hybrid form of critical practice that brings “nuclear criticism”—a subfield of literary studies that has been, since the Cold War, largely neglected—into conversation with ecocriticism, the more recent approach to environmental texts in literary studies. Through readings of novels, films, theater, poetry, visual art, websites, news reports, and essays, 'Risk Criticism' tracks the diverse ways in which environmental risks are understood and represented today.

Conversations with children on the Gospels;

Also available in microfilm from Xerox University Microfilms, Ann Arbor, Mich., 1972, in the series: American Culture Series, reel 531.11.

SITE 1121 - FIELD NOTES Revealing Deep Form as a Basis for Urban Landscape Design

Thesis (Master's)--University of Washington, 2016-06

Mechanism of α-defensin HD5 Inhibition of Human Papillomavirus-16

Thesis (Ph.D.)--University of Washington, 2016-06