Role of aromatic residues in stabilization of the [Fe4S4] cluster in high-potential iron proteins (HiPIPs): physical characterization and stability studies of Tyr-19 mutants of Chromatium vinosum HiPIP.

The functional role of residue Tyr-19 of Chromatium vinosum HiPIP has been evaluated by site-directed mutagenesis experiments. The stability of the [Fe4S4] cluster prosthetic center is sensitive to side-chain replacements. Polar residues result in significant instability, while nonpolar residues (especially with aromatic side chains) maintain cluster stability. Two-dimensional NMR data of native and mutant HiPIPs are consistent with a model where Tyr-19 serves to preserve the structural rigidity of the polypeptide backbone, thereby maintaining a hydrophobic barrier for exclusion of water from the cluster cavity. Solvent accessibility results in more facile oxidation of the cluster by atmospheric oxygen, with subsequent rapid hydrolysis of the [Fe4S4]3+ core.

DNA recombination is sufficient for retroviral transduction.

Oncogenic retroviruses carry coding sequences that are transduced from cellular protooncogenes. Natural transduction involves two nonhomologous recombinations and is thus extremely rare. Since transduction has never been reproduced experimentally, its mechanism has been studied in terms of two hypotheses: (i) the DNA model, which postulates two DNA recombinations, and (ii) the RNA model, which postulates a 5' DNA recombination and a 3' RNA recombination occurring during reverse transcription of viral and protooncogene RNA. Here we use two viral DNA constructs to test the prediction of the DNA model that the 3' DNA recombination is achieved by conventional integration of a retroviral DNA 3' of the chromosomal protooncogene coding region. For the DNA model to be viable, such recombinant viruses must be infectious without the purportedly essential polypurine tract (ppt) that precedes the 3' long terminal repeat (LTR) of all retroviruses. Our constructs consist of a ras coding region from Harvey sarcoma virus which is naturally linked at the 5' end to a retroviral LTR and artificially linked at the 3' end either directly (construct NdN) or by a cellular sequence (construct SU) to the 5' LTR of a retrovirus. Both constructs lack the ppt, and the LTR of NdN even lacks 30 nucleotides at the 5' end. Both constructs proved to be infectious, producing viruses at titers of 10(5) focus-forming units per ml. Sequence analysis proved that both viruses were colinear with input DNAs and that NdN virus lacked a ppt and the 5' 30 nucleotides of the LTR. The results indicate that DNA recombination is sufficient for retroviral transduction and that neither the ppt nor the complete LTR is essential for retrovirus replication. DNA recombination explains the following observations by others that cannot be reconciled with the RNA model: (i) experimental transduction is independent of the packaging efficiency of viral RNA, and (ii) experimental transduction may invert sequences with respect to others, as expected for DNA recombination during transfection.

Imaging of spin waves in atomically designed nanomagnets

The spin dynamics of all ferromagnetic materials are governed by two types of collective phenomenon: spin waves and domain walls. The fundamental processes underlying these collective modes, such as exchange interactions and magnetic anisotropy, all originate at the atomic scale. However, conventional probing techniques based on neutron1 and photon scattering2 provide high resolution in reciprocal space, and thereby poor spatial resolution. Here we present direct imaging of standing spin waves in individual chains of ferromagnetically coupled S = 2 Fe atoms, assembled one by one on a Cu2N surface using a scanning tunnelling microscope. We are able to map the spin dynamics of these designer nanomagnets with atomic resolution in two complementary ways. First, atom-to-atom variations of the amplitude of the quantized spin-wave excitations are probed using inelastic electron tunnelling spectroscopy. Second, we observe slow stochastic switching between two opposite magnetization states3, 4, whose rate varies strongly depending on the location of the tip along the chain. Our observations, combined with model calculations, reveal that switches of the chain are initiated by a spin-wave excited state that has its antinodes at the edges of the chain, followed by a domain wall shifting through the chain from one end to the other. This approach opens the way towards atomic-scale imaging of other types of spin excitation, such as spinon pairs and fractional end-states5, 6, in engineered spin chains.

In Search of a Feasible EU-Mercosul Free Trade Agreement. CEPS Working Document No. 378, 25 February 2013

This paper aims at identifying ways to pursue the EU–Mercosul negotiations leading to a free trade agreement (FTA). After reviewing their already long history, it outlines a basic framework, in goods, services and other themes, judged possible. The main point is that, given the prevailing conditions on both sides, an agreement to be signed within a reasonable time must be modest, i.e. along the described lines. It then clearly sets up the decisions confronting the negotiators: either to pursue the modest, feasible option or to terminate negotiations under the FTA heading. The latter, however, does not imply an end to the dialogue. Many actions and measures may be taken – which are easier to discuss and fix – that could pave the way for, in due time, a closer-to-ideal FTA to be considered again. These are the subjects of a last section.

Helpless and lonely: Turkey's attitude towards the war in Syria. OSW Commentary No. 136, 09.05.2014

The conflict in Syria, which has lasted since 2011, has become the most significant test of the efficiency of Turkey’s foreign policy and the biggest challenge to Turkey’s security in recent decades. The lack of a clear prospect of an end to the war does not allow us to come to a final conclusion regarding the Syrian civil war’s importance for Turkey. However, it can be said today that with the exception of the initial phase of the conflict, Ankara’s influence over the course of events in Syria has been limited, and the war itself is evolving in a direction that is unfavourable for Turkey: the hostile regime of Bashar al-Assad is still in power, the opposition has proved to be an unreliable or even a dangerous ally, and in northern Syria militant jihadist groups and Kurds are gaining importance. It is also quite unlikely that the West will take any greater responsibility for stabilising the situation in the region. In response to such an unfortunate situation, and out of fear of risking deeper involvement in the conflict, during the past year Turkey’s policy towards Syria has been restrained, reactive and focused mainly on defending Turkey’s territory. However, this policy offers no security guarantees and does not prevent the country’s regional position from weakening, especially in the context of the reinforcement of the jihadist militants and the Kurdish autonomy in northern Syria. The arguments for Turkey continuing its defensive policy are strong: the country fears the possible results of an open confrontation with Assad’s forces; most probably it could not count on support for such actions from within its own society or its Western allies. It also does not have enough acceptance within the anti-Assad opposition circles. On the other hand, though, the risk of uncontrolled development of events is still present; the risk of confrontations with armed jihadist militants is growing; and the potential operation of Turkish forces, either against the jihadists or against Assad’s army, could be considered as a method of diverting attention from the political problems with which the AKP government has been struggling at home.

The Economics of EU Railway Reform. Bruges European Economic Policy (BEEP) Briefing 8/2004

The EU began railway reform in earnest around the turn of the century. Two ‘railway packages’ have meanwhile been adopted amounting to a series of directives and a third package has been proposed. A range of complementary initiatives has been undertaken or is underway. This BEEP Briefing inspects the main economic aspects of EU rail reform. After highlighting the dramatic loss of market share of rail since the 1960s, the case for reform is argued to rest on three arguments: the need for greater competitiveness of rail, promoting the (market driven) diversion of road haulage to rail as a step towards sustainable mobility in Europe, and an end to the disproportional claims on public budgets of Member States. The core of the paper deals respectively with market failures in rail and in the internal market for rail services; the complex economic issues underlying vertical separation (unbundling) and pricing options; and the methods, potential and problems of introducing competition in rail freight and in passenger services. Market failures in the rail sector are several (natural monopoly, economies of density, safety and asymmetries of information), exacerbated by no less than 7 technical and legal barriers precluding the practical operation of an internal rail market. The EU choice to opt for vertical unbundling (with benefits similar in nature as in other network industries e.g. preventing opaque cross-subsidisation and greater cost revelation) risks the emergence of considerable coordination costs. The adoption of marginal cost pricing is problematic on economic grounds (drawbacks include arbitrary cost allocation rules in the presence of large economies of scope and relatively large common costs; a non-optimal incentive system, holding back the growth of freight services; possibly anti-competitive effects of two-part tariffs). Without further detailed harmonisation, it may also lead to many different systems in Member States, causing even greater distortions. Insofar as freight could develop into a competitive market, a combination of Ramsey pricing (given the incentive for service providers to keep market share) and price ceilings based on stand-alone costs might be superior in terms of competition, market growth and regulatory oversight. The incipient cooperative approach for path coordination and allocation is welcome but likely to be seriously insufficient. The arguments to introduce competition, notably in freight, are valuable and many e.g. optimal cross-border services, quality differentiation as well as general quality improvement, larger scale for cost recovery and a decrease of rent seeking. Nevertheless, it is not correct to argue for the introduction of competition in rail tout court. It depends on the size of the market and on removing a host of barriers; it requires careful PSO definition and costing; also, coordination failures ought to be pre-empted. On the other hand, reform and competition cannot and should not be assessed in a static perspective. Conduct and cost structures will change with reform. Infrastructure and investment in technology are known to generate enormous potential for cost savings, especially when coupled with the EU interoperability programme. All this dynamism may well help to induce entry and further enlarge the (net) welfare gains from EU railway reform. The paper ends with a few pointers for the way forward in EU rail reform.

Grexit 2015: A primer. CEPS Commentary, 22 January 2015

In the run-up to the Greek elections on January 25th and the subsequent renegotiation of the country's economic adjustment programme with the troika, Daniel Gros writes in this Commentary that "nobody officially wants Grexit": not Syriza, which wants Greece to stay in the euro. It is ‘only’ asking for a reduction in Greece’s official debt and an end to austerity. The German government also does not favour Grexit because European unification remains the central project for German policy-makers across all mainstream parties. Only some protest parties and vocal economists think Greece (and Germany) would better off with a new Drachma. In his view, the substantive issues are thus the demands for a reduction of the official debt of Greece and an end to austerity, both of which he describes as eminently fudgeable. In any event, change in policy will be minor if a Syriza government is as successful in fulfilling its promise to spend as the previous government was in promising not to spend.

Putin: The morally depraved degradation of a strong state leader. CEPS Commentary, 31 March 2015

In a new CEPS Commentary, Michael Emerson calls for an end to diplomatic euphemisms in describing Putin’s tragic degradation of Russia, its political regime and society. The assassination of Boris Nemtsov on February 27th signals one more step down this dreadful path.

After a nuclear deal: What next for Iranian oil and gas? EPC Policy Brief, 23 June 2015

On 2 April in Lausanne, after months of intense negotiations, Iran and the E3+3 (France, Germany, and the UK plus China, Russia, and the US) agreed on a framework deal for the resolution of the nuclear dispute. EU High Representative for Foreign Affairs and Security Policy, Federica Mogherini, and Iran's Foreign Minister, Mohammad Javad Zarif, issued a joint statement announcing that "solutions on key parameters of a Joint Comprehensive Plan of Action" have been found. While differences remain on several issues, including the scope of International Atomic Energy Agency (IAEA) inspections and sanctions relief, the statement has nevertheless raised hopes that a final deal may be reached this summer. If accomplished, an agreement would bring an end to more than a decade of tensions between Iran and the international community. This would result in the lifting of several sanctions, which were adopted against Iran by the United Nations, the EU, and the US. Unsurprisingly therefore, Iran's economy and in particular its energy sector are now the subject of worldwide attention.

Flashlight Europe N°3–April 2015. Greece – What else?

The first hundred days in office have become a benchmark for every new government. Early in May, the Tsipras coalition government will reach this date. Given the difficult financial, economic and social situation in Greece, there was no such thing as a closed season for Alexis Tsipras from day one on, and he himself could not have expected one. After all, his new government acceded office with a political agenda demanding nothing less than an end to austerity and the submission to a reform programme seen as unduly imposed on Greece by its creditors, the EU and the IMF.

"Where is the Wealth?" Echoing the King's 2014 speech in light of the delay in the implementation of the new Constitution. Arab Citizenship Review No. 16, 19 February 2016

In Morocco, the new Constitution promised by King Mohammed VI in 2011 has raised high expectations regarding the improvement of socio-economic standards in the country and the possible redistribution of national wealth in a more transparent and democratic way. Just like Tunisia and Egypt, Moroccan demonstrators of the 20 February Movement had taken to the streets to ask for more freedom and democracy, but also to call for social equality and an end to corruption. Many of the grievances and the claims raised by demonstrators fell within the domain of socio-economic rights. Even though it might still be early to take stock, five years down the road, it is possible to provide a fist assessment of the major changes in Morocco in the socio-economic area. The attempt is to analyse whether the improvements introduced by the new Constitution have met the expectations of the people standing up for their rights in the wake of the Arab Spring, or whether the Kingdom of Morocco has fallen short on its promise to undertake structural change.

The Interregional Association Agreement between the European Union and Mercosur: Is the Timing Right? Bruges Political Research Papers 46/2015.

The European Union (EU) and Mercosur talks have been stalled since discussions were resumed in 2000. Recurring protectionist and institutional obstacles have slowed down negotiations. The financial crisis, however, has resulted in low domestic demand in the EU. This has made the interregional association agreement (IAA) with Mercosur more attractive. The loss of the Generalized Scheme of Preference (GSP) status and the lack of a Free Trade Agreement (FTA) with the EU have both disadvantaged Mercosur. A further window of opportunity is opening up in Mercosur. In Brazil, there have been cries for a change in government. In Argentina, presidential elections will take place in October 2015 and will assuredly bring an end to Kirchnerismo. A change in leadership in both countries is expected to make agreement more likely. Protectionist policies are not expected to remain as high if there is change in government. This will provide the EU with an opportunity to advance the negotiations and conclude the IAA.

Selbstbestimmung und Parteien in Südtirol: Territoriale und europäische Parteistrategien zwischen Autonomie und Sezession = Self-determination and parties in South Tyrol: Territorial and European party strategies between autonomy and secession. EDAP Paper 03/2016 03/2016

Since the final conflict settlement between Italy and Austria in 1992, ethnic politics in South Tyrol experienced insightful transformations. The consociational political system, which was implemented to tame centrifugal tendencies, has been losing its balance over the last decade, with proautonomy stances ceding ground to secessionist pressure in the Germanspeaking intra-ethnic arena. Adopting a contextual and strategic perspective on self-determination, this article traces the evolution of ethno-regionalist party strategies on the territorial and European dimension of party competition through a quantitative and qualitative content analysis of their electoral manifestos in the period between 1993 and 2013. In line with newest research on party strategies, the article empirically shows the strategic capacity of ethnic minority parties to challenge each other not only by shifting their positions on the different issue dimensions but also by the reframing of issues. While the increasing competition on the center-periphery axis leads to a new territorial frame, the rise of secessionism is accompagned by an end to the pro-European elite consensus.

Propofol sedation administered by cardiologists for patients undergoing catheter ablation for ventricular tachycardia

AIMS Propofol sedation has been shown to be safe for atrial fibrillation ablation and internal cardioverter-defibrillator implantation but its use for catheter ablation (CA) of ventricular tachycardia (VT) has yet to be evaluated. Here, we tested the hypothesis that VT ablation can be performed using propofol sedation administered by trained nurses under a cardiologist's supervision. METHODS AND RESULTS Data of 205 procedures (157 patients, 1.3 procedures/patient) undergoing CA for sustained VT under propofol sedation were analysed. The primary endpoint was change of sedation and/or discontinuation of propofol sedation due to side effects and/or haemodynamic instability. Propofol cessation was necessary in 24 of 205 procedures. These procedures (Group A; n = 24, 11.7%) were compared with those with continued propofol sedation (Group B; n = 181, 88.3%). Propofol sedation was discontinued due to hypotension (n = 22; 10.7%), insufficient oxygenation (n = 1, 0.5%), or hypersalivation (n = 1, 0.5%). Procedures in Group A were significantly longer (210 [180-260] vs. 180 [125-220] min, P = 0.005), had a lower per hour propofol rate (3.0 ± 1.2 vs. 3.8 ± 1.2 mg/kg of body weight/h, P = 0.004), and higher cumulative dose of fentanyl administered (0.15 [0.13-0.25] vs. 0.1 [0.05-0.13] mg, P < 0.001), compared with patients in Group B. Five (2.4%) adverse events occurred. CONCLUSION Sedation using propofol can be safely performed for VT ablation under the supervision of cardiologists. Close haemodynamic monitoring is required, especially in elderly patients and during lengthy procedures, which carrying a higher risk for systolic blood pressure decline.

Edge caching with mobility prediction in virtualized LTE mobile networks

Abstract Mobile Edge Computing enables the deployment of services, applications, content storage and processing in close proximity to mobile end users. This highly distributed computing environment can be used to provide ultra-low latency, precise positional awareness and agile applications, which could significantly improve user experience. In order to achieve this, it is necessary to consider next-generation paradigms such as Information-Centric Networking and Cloud Computing, integrated with the upcoming 5th Generation networking access. A cohesive end-to-end architecture is proposed, fully exploiting Information-Centric Networking together with the Mobile Follow-Me Cloud approach, for enhancing the migration of content-caches located at the edge of cloudified mobile networks. The chosen content-relocation algorithm attains content-availability improvements of up to 500 when a mobile user performs a request and compared against other existing solutions. The performed evaluation considers a realistic core-network, with functional and non-functional measurements, including the deployment of the entire system, computation and allocation/migration of resources. The achieved results reveal that the proposed architecture is beneficial not only from the users’ perspective but also from the providers point-of-view, which may be able to optimize their resources and reach significant bandwidth savings.