The hard-soft acid-base principle in enzymatic catalysis: dual reactivity of phosphoenolpyruvate.

In this paper, the chemical reactivity of C3 of phosphoenolpyruvate (PEP) has been analyzed in terms of density functional theory quantified through quantum chemistry calculations. PEP is involved in a number of important enzymatic reactions, in which its C3 atom behaves like a base. In three different enzymatic reactions analyzed here, C3 sometimes behaves like a soft base and sometimes behaves like a hard base in terms of the hard-soft acid-base principle. This dual nature of C3 of PEP was found to be related to the conformational change of the molecule. This leads to a testable hypothesis: that PEP adopts particular conformations in the enzyme-substrate complexes of different PEP-using enzymes, and that the enzymes control the reactivity through controlling the dihedral angle between the carboxylate and the C==C double bond of PEP.

Multiwavelength study of quiescent states of MrK 421 with unprecedented hard x-Ray coverage provided by NuStar in 2013

We present coordinated multiwavelength observations of the bright, nearby BL Lacertae object Mrk 421 taken in 2013 January–March, involving GASP-WEBT, Swift, NuSTAR, Fermi-LAT, MAGIC, VERITAS, and other collaborations and instruments, providing data from radio to very high energy (VHE) γ-ray bands. NuSTAR yielded previously unattainable sensitivity in the 3–79 keV range, revealing that the spectrum softens when the source is dimmer until the X-ray spectral shape saturates into a steep G » 3 power law, with no evidence for an exponential cutoff or additional hard components up "aprox" 80keV. For the first time, we observed both the synchrotron and the inverse-Compton peaks of the spectral energy distribution (SED) simultaneously shifted to frequencies below the typical quiescent state by an order of magnitude. The fractional variability as a function of photon energy shows a double-bump structure that relates to the two bumps of the broadband SED. In each bump, the variability increases with energy, which, in the framework of the synchrotron self-Compton model, implies that the electrons with higher energies are more variable. The measured multi band variability, the significant X-ray-toVHE correlation down to some of the lowest fluxes ever observed in both bands, the lack of correlation between optical/UV and X-ray flux, the low degree of polarization and its significant (random) variations, the short estimated electron cooling time, and the significantly longer variability timescale observed in the NuSTAR light curves point toward in situ electron acceleration and suggest that there are multiple compact regions contributing to the broadband emission of Mrk 421 during low-activity states.

Equilibrium fluid-solid coexistence of hard spheres

We present a tethered Monte Carlo simulation of the crystallization of hard spheres. Our method boosts the traditional umbrella sampling to the point of making practical the study of constrained Gibbs’ free energies depending on several crystalline order parameters. We obtain high-accuracy estimates of the fluid-crystal coexistence pressure for up to 2916 particles (enough to accommodate fluid-solid interfaces). We are able to extrapolate to infinite volume the coexistence pressure [p_(co) = 11.5727(10)k_(B)T/σ^(3)] and the interfacial free energy [γ_({100}) = 0.636(11)k_(B)T/σ^(2)].

Affordable Environmental Cleanup Actions at Abandoned Hard Rock Mine Sites

Abandoned mine land cleanups are limited by restrictive regulations, inconsistent and unavailable funds, and a lack of adequate protections for stakeholders attempting to improve site conditions. This study evaluated examples of two cleanup mechanisms: an EPA-lead CERCLA cleanup and a state-lead, stakeholder-funded approach. The case studies showed that CERCLA provides the most comprehensive funding mechanism for abandoned mine cleanups while offering very little flexibility. State-lead programs allow for more flexibility, yet states are bound by federal laws and are hampered by lack of funding. Case analysis determined that any new approach should provide adequate funding, be flexible in its cleanup criteria, and minimize liability for those undertaking cleanups. It must also protect human health and promote natural ecological recovery.

A systematic study on the influence of carbon on the behavior of hard-to-ionize elements in inductively coupled plasma–mass spectrometry

A systematic study on the influence of carbon on the signal of a large number of hard-to-ionize elements (i.e. B, Be, P, S, Zn, As, Se, Pd, Cd, Sb, I, Te, Os, Ir, Pt, Au, and Hg) in inductively coupled plasma–mass spectrometry has been carried out. To this end, carbon matrix effects have been evaluated considering different plasma parameters (i.e. nebulizer gas flow rate, r.f. power and sample uptake rate), sample introduction systems, concentration and type of carbon matrix (i.e. glycerol, citric acid, potassium citrate and ammonium carbonate) and type of mass spectrometer (i.e. quadrupole filter vs. double-focusing sector field mass spectrometer). Experimental results show that P, As, Se, Sb, Te, I, Au and Hg sensitivities are always higher for carbon-containing solutions than those obtained without carbon. The other hard-to-ionize elements (Be, B, S, Zn, Pd, Cd, Os, Ir and Pt) show no matrix effect, signal enhancement or signal suppression depending on the experimental conditions selected. The matrix effects caused by the presence of carbon are explained by changes in the plasma characteristics and the corresponding changes in ion distribution in the plasma (as reflected in the signal behavior plot, i.e. the signal intensity as a function of the nebulizer gas flow rate). However, the matrix effects for P, As, Se, Sb, Te, I, Au and Hg are also related to an increase in analyte ion population caused as a result of charge transfer reactions involving carbon-containing charged species in the plasma. The predominant specie is C+, but other species such as CO+, CO2+, C2+ and ArC+ could also play a role. Theoretical data suggest that B, Be, S, Pd, Cd, Os, Ir and Pt could also be involved in carbon based charge transfer reactions, but no experimental evidence substantiating this view has been found.

Juncker’s Mission to the New Energy Team: Avoiding the hard choices. CEPS Commentary, 24 September 2014

In his mission letter to Arias Cañete, Jean-Claude Juncker asked the designated Commissioner for Climate Action and Energy to focus on further developing EU policy for renewables in order to “be a world leader in this sector” and on promoting the EU Emissions Trading System “to ensure that we reach our climate goals in a cost-effective way”. Furthermore, he would like Alenka Bratušek, the designated Vice-President for Energy Union, to focus on “completing the internal energy market” and on “increasing competition”. In assessing the feasibility and desirability of this remit, this commentary finds these objectives to be very ambitious but more importantly, partially conflicting, given the state of play in EU energy markets.

The Transatlantic Trade and Investment Partnership: A long hard road to multilateralism? EPC Commentary, 26 September 2014

The seventh round of the Transatlantic Trade and Investment Partnership (TTIP) negotiations between the European Union and the United States will take place in Washington on 29 September. If concluded successfully, the TTIP would become the world’s largest free trade pact. The EU and the US account for nearly half of the world’s GDP and 30% of world trade with exchanges of goods and services worth around €723 billion a year and €1.8 billion a day. The Partnership, unprecedented in its scope and ambition, has generated great expectations which will be hard to meet in reality. It could however have a beneficial effect on trade multilateralism, provided that it is the result of an open negotiating process.

Russia in Serbia – soft power and hard interests. OSW COMMENTARY No. 150, 2014-10-29

Russian President Vladimir Putin’s visit to Serbia on 16 October has demonstrated Moscow’s willingness to secure its interests in the Balkans and use Belgrade in its confrontation with the West. It seems, however, that Russia does not have much to offer to Serbia’s authorities, which are reluctant to make more concessions towards Russia. However, Moscow has already gained a strong position in Serbia, which is due to the country’s dependence on Russian natural resources and, in particular, strong support for Russian policy on the part of Serbian elites and society. The traditional pro-Russian attitudes have been strengthened as a result of a series of Russia-inspired, wide-ranging soft power initiatives which have proved so successful that a large part of society has begun to believe that Russia’s interests are consistent with Serbia’s. Russia’s increasingly active policy towards Serbia and the Serbian minorities in the neighbouring countries – Bosnia and Herzegovina, Montenegro and Kosovo – has been part of a larger plan aimed at hampering the integration of the Balkan states with the Euro-Atlantic structures and maintaining an area of instability and frozen conflicts in the EU’s near neighbourhood. Russia’s policy is also becoming increasingly effective due to the EU states’ diminishing support for Balkan countries’ European integration.

The fiscal compact - Europe's "hard core" based on German economic conditions. OSW Commentary No. 71, 2012-03-07

On 2 March, the leaders of 25 EU member states signed the Treaty on stability, coordination and governance in the economic and monetary union. It will introduce new fiscal constraints and officially vest new competences in the eurozone countries. Thus, their right to coordinate economic policy among them will be sanctioned. So far, the Lisbon Treaty has only provided for organisation of informal Eurogroup meetings, to be attended by representatives of the European Commission. The principles introduced by the compact, if the eurozone countries are really determined to observe its provisions, will create a new way of managing the single currency. Within the next few years, the most indebted countries will have to carry out radical reforms to boost their competitiveness and adjust it to German standards. During this period the Federal Republic of Germany will most probably decide to offer higher loan guarantees to relieve these countries’ budgets. The compact’s political consequences are also of great significance, especially considering how the treaty was finalised. The eurozone states have in fact accepted that the direction for changes will be devised by France and Germany, and the role of European institutions such as the Commission or the Parliament may weaken. From the perspective of eurozone candidate countries, the introduction of the fiscal compact means expanding the scope of conditions they must meet to become members of the single currency area. In the future, a country, in order to adopt the single currency, will have to meet the structural deficit criterion, and also most probably carry out economic reforms such as unifying its fiscal system. These goals will be achieved across the eurozone gradually, in the subsequent stages of the economic governance reform.

TTIP’s Hard Core: Technical barriers to trade and standards. Paper No. 13 in the CEPS-CTR project ‘TTIP in the Balance’ and CEPS Special Report No. 117/August 2015

Michelle Egan and Jacques Pelkmans provide an overview of the TBT chapter in TTIP and the various issues between the US and the EU in this area, which in turn requires extensive expositions of domestic regulation in the US and the EU. TBTs, outside heavily regulated sectors such as chemicals, automobiles or medicines (which have separate chapters in TTIP), can be caused by divergent (voluntary) standards, technical regulations and conformity assessment. Indeed, in all three the US and the EU have long experienced frictions with considerable trading costs. The 1998 Mutual Recognition Agreement about conformity assessment only succeeded in two out of six sectors. The US and European standardisation traditions differ and this paper explains why it is so hard, also economically, to realise convergence. However, the authors reject the unproductive ‘stand-off’ between US and EU negotiators on standardisation and suggest to clarify the enormous economic ‘installed base’ of prominent US standards in the world economy and build a solution from there. As to technical regulation, the prospect of converging regulation (via harmonisation) is often dim, but equivalence (given similar levels of regulatory protection) can be an option.

China's Confidence Issue: Hard or Smart Landing - What Can We Expect? Asia Policy Brief 2015/03, November 2015

A China whose economy is growing at a slower pace is something the world can cope with. But a China with doubts about whether the government can maintain control and implement reform – that would be a serious problem. The signals currently coming from the economic and political spheres are cause for concern. China is in danger of falling into a downward spiral of declining confidence. What are the consequences for Germany?

Soft or hard Brexit? EPC Commentary, 15 July 2016

The EU is in uncharted waters when it comes to negotiating the UK’s exit from the Union. Creative and flexible thinking will be required from all parties if an orderly departure is to be managed. The alternative is a fractious, mutually damaging and disorderly Brexit. This commentary argues for a short-term, time-limited agreement to stabilise the EU-UK relationship and to allow breathing space to develop the terms of a long-term strategic partnership.

COPD: A stepwise or a hit hard approach?

Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach.