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Inelastic neutron scattering (INS) is employed to examine the evolution of a promoter-free iron-based Fischer–Tropsch synthesis catalyst (∼10 g catalyst charge) that is exposed to ambient pressure CO hydrogenation at 623 K for up to 10 days time-on-stream (T-o-S). The longer reaction time is selected to better understand how the formation of a previously described hydrocarbonaceous overlayer corresponds to the catalyst conditioning process. Although the onset of pseudo steady-state reactor performance is observed at approximately 9 h T-o-S, INS establishes that the intensity of the C–H stretching mode of the sp3-hybridized component of the hydrocarbonaceous overlayer saturates at about 24 h T-o-S, while the corresponding intensity of the C–H stretching mode of the sp2-hybridized component requires 100–200 h T-o-S to achieve saturation. This novel series of measurements reveal different aspects of the complex catalyst evolutionary process to be indirectly connected with catalytic turnover.

Resistance to clinical antiandrogens has plagued the evolution of effective therapeutics for advanced prostate cancer. As with the first-line therapeutic bicalutamide (Casodex), resistance to newer antiandrogens (enzalutamide, ARN-509) develops quickly in patients, despite the fact that these drugs have ∼10-fold better affinity for the androgen receptor than bicalutamide. Improving affinity alone is often not sufficient to prevent resistance, and alternative strategies are needed to improve antiandrogen efficacy. Covalent and reversible covalent drugs are being used to thwart drug resistance in other contexts, and activated aryl nitriles are among the moieties being exploited for this purpose. We capitalized on the presence of an aryl nitrile in bicalutamide, and the existence of a native cysteine residue (Cys784) in the androgen receptor ligand binding pocket, to develop 5N-bicalutamide, a cysteine-reactive antiandrogen. 5N-bicalutamide exhibits a 150-fold improvement in Kiand 20-fold improvement in IC50over the parent compound. We attribute the marked improvement in affinity and activity to the formation of a covalent adduct with Cys784, a residue that is notamong the more than 160 androgen receptor point mutations associated with prostate cancer. Increasing the residence time of bound antiandrogen via formation of a covalent adduct may forestall the drug resistance seen with current clinical antiandrogens.

The mechanism of chemical reactions between adsorbed species is defined by the combined effects of the adsorbate–substrate potential landscape and lateral interactions. Such lateral interactions are therefore integral to catalytic processes, but their study is often complicated by “substrate mediation”, the regulation of a two-body potential between adsorbed particles by the surface itself. Substrate mediation can influence the sign and magnitude of lateral interactions. There are notable exceptions of ordered structures forming at low coverage, indicative of short-range attractive forces where repulsive forces are expected to dominate, suggesting a strong substrate-mediated contribution. To explore further the origins of such interactions, we have investigated the adsorption of CO on Cu(110) using a combination of low-temperature microscopy and first-principles calculations. Our studies reveal that lateral adsorbate interactions, which are constrained by the metal surface, regulate the bonding between the adsorbate and substrate. Anisotropic CO–CO coupling is seen to arise from a perfect balance between the intermolecular accumulation of charge that acts as a glue (chemical coupling) at sufficiently large distances to avoid repulsive effects (dipole–dipole coupling and Pauli’s repulsion between electron clouds).

IntroduzioneIn this article, we seek to re-consider the ‘presidentialization of politics’ argument in the light of recent developments in Germany and the United Kingdom. The experiences of coalition government suggest prima faciegrounds for the erosion of the presidentialization process in each country. Germany has operated with a Grand Coalition in which domination of the executive by the Chancellor would seem less likely, whereas the long history of single-party governments in the United Kingdom gave way to a rare experiment in coalitional power sharing between 2010 and 2015, circumstances which should limit prime ministerial power. However, it is our contention that the presidentialization thesis retains its purchase in these two countries. German Chancellors and British prime ministers have been increasingly able to mobilize power resources, which allow them to govern more independently of their own parties and their coalition partners, and this seems to hold across a variety of political circumstances.

Isotopic enrichment of 29Si and DNP-enhanced NMR spectroscopy are combined to determine the detailed surface structure of a silicated alumina catalyst. The significant sensitivity enhancement provided by DNP is vital to the acquisition of multinuclear and multidimensional experiments that provide information on the atomic-level structure of the species present at the surface. Isotopic enrichment not only facilitates spectral acquisition, particularly given the low (1.5 wt %) Si loading, but also enables spectra with higher resolution than those acquired using DNP to be obtained. The unexpected similarity of conventional, CP, and DNP NMR spectra is attributed to the presence of adventitious surface water that forms a sufficiently dense 1H network at the silica surface so as to mediate efficient polarization transfer to all Si species regardless of their chemical nature. Spectra reveal the presence of Si–O–Si linkages at the surface (identified as Q4(3Al)–Q4(3Al)) and confirm that the anchoring of the surface overlayer with the alumina occurs through AlIVand AlVspecies only. This suggests the presence of Q3/Q4Si at the surface affects the neighboring Al species, modifying the surface structure and making it less likely AlVIenvironments are in close spatial proximity. In contrast, Q1/Q2species, bonded to the surface by fewer covalent bonds, have less of an effect on the surface, and more AlVIspecies are consequently found nearby. The combination of isotropic enrichment and DNP provides a definitive and fully quantitative description of the Si-modified alumina surface, and we demonstrate that almost one-third of the silicon at the surface is connected to another Si species, even at the low level of coverage used, lowering the propensity for the formation of Brønsted acid sites. This suggests that a variation in the synthetic procedure might be required to obtain a more even coverage for optimum performance. The work here will allow for more rigorous future investigations of structure–function relationships in these complex materials.

The functional conversion of white adipose tissue (WAT) into a tissue with brown adipose tissue (BAT)-like activity, often referred to as “browning,” represents an intriguing strategy for combating obesity and metabolic disease. We demonstrate that thyroid hormone receptor (TR) activation by a synthetic agonist markedly induces a program of adaptive thermogenesis in subcutaneous WAT that coincides with a restoration of cold tolerance to cold-intolerant mice. Distinct from most other browning agents, pharmacological TR activation dissociates the browning of WAT from activation of classical BAT. TR agonism also induces the browning of white adipocytes in vitro, indicating that TR-mediated browning is cell autonomous. These data establish TR agonists as a class of browning agents, implicate the TRs in the browning of WAT, and suggest a profound pharmacological potential of this action.

IntroduzioneChanges in electoral politics in contemporary democracies have contributed to shifting the focus of research from parties to individual candidates. The 2013 Italian Candidate Survey (ICS) has collected original survey data with the aim of gaining new insights into the role of political elites, looking in particular at the candidates running for office in the last Italian general election. Based on interviews with individual candidates, the ICS provides a tool for analysing party members; and for comparing them with voters in several ways. In this paper, we spell out the main features of our research that was conducted within the framework of a larger project that examined political representation in Italy between 2013 and 2015. Moreover, we offer three examples of potential applications of ICS data. First, we present a model of political representation favoured by Italian candidates that matches with a well-known typology of political representation. Second, we utilize our ICS data to estimate candidates’ policy preferences and to assess the level of congruence with their voters. Finally, by comparing the distribution of candidates’ self-placements and their own party mean position on the left-right scale, we show how our data can be used to explore intra-party cohesion.

IntroduzioneParty leaders have become more powerful and autonomous actors in recent years by developing a direct and personal relationship with citizens. As anticipated in the United States (Lowi, 1985), the rise of the ‘personal leader’ seems to have occurred in many European democracies, both in old parties and in more recently formed parties, with a widespread tendency for them to be promoted and controlled by individual leaders. Nevertheless, party leadership remains quite a neglected theme in political science. Through a data set including ~500 party presidents in 13 democracies, this article focusses on the personalization of party leadership by comparing Italy with other Western countries. More particularly, new procedures for the selection of party chairs, the centralization of power in political parties, and the new role of party leaders in the legislative/governmental arena are analysed, given their importance to such a process. The article summarizes new data on the party leaders’ characteristics, with regards to their political backgrounds, how they are elected, how long they stay in office, and whether they become prime minister or enter the executive. In this way, we are able to see how some new parties are created from the outset as highly personalized and centralized parties (Forza Italia being the paradigmatic case), whereas other older parties have also evolved in a personalized direction.

IntroduzioneAfter sharing, through its various steps of evolution, the form and status of a corporate body, the party organization is falling prey to the virus of personalization, which is invading so many realms of contemporary life. Italy provides the clearest example of this cross-national trend with Silvio Berlusconi’s personal party. As a media tycoon and one of the wealthiest men in the world, Berlusconi could rely on a skilled professional apparatus as well as on huge financial means to set up, in a few months, a vote-generating machine and become a Prime Minister. His party model has been widely imitated, by both center-right and center-left organizations, with variations and deviations. This article presents an overview of the development of personal parties in Italy and an analytical framework based on Max Weber’s types of personal power.

IntroduzioneCentral Eastern European party politics offers a good example of the trend towards centralizing internal party decision making, as well as encouraging strong personalities in the role of party leader. This trend is visible in all three major spheres of party activity: election campaigning, the internal organization of parties, and governmental politics. This paper focusses on the party systems of the Czech Republic, Hungary, Poland, Slovakia, and Slovenia to demonstrate that there are actually two processes of presidentialization that occur in party politics. On the one hand, the role of the leader is gaining importance in more traditional, well-established parties such as the Civic and Social Democrats in the Czech Republic and Fidesz in Hungary. On the other hand, perhaps an even clearer presidentialization process is evident in the emergence of new protest parties focussed around strong personalities that often make no attempt to establish and maintain a more complex internal party organization.

In fish otoliths, CaCO3 normally precipitates as aragonite, and more rarely as vaterite or calcite. A higher incidence of vaterite deposition in otoliths from aquaculture-reared fish has been reported and it is thought that high growth rates under farming conditions might promote its deposition. To test this hypothesis, otoliths from growth hormone (GH) transgenic coho salmon and non-transgenic fish of matching size were compared. Once morphometric parameters were normalized by animal length, we found that transgenic fish otoliths were smaller (−24%, −19%, −20% and −30% for length, width, perimeter and area, respectively; P<0.001) and rounder (−12%, +13.5%, +15% and −15.5% in circularity, form factor, roundness and ellipticity; P<0.001) than otoliths from non-transgenic fish of matching size. Interestingly, transgenic fish had smaller eyes (−30% eye diameter) and showed a strong correlation between eye and otolith size. We also found that the percentage of otoliths showing vaterite deposition was significantly smaller in transgenic fish (21–28%) than in non-transgenic fish (69%; P<0.001). Likewise, the area affected by vaterite deposition within individual otoliths was reduced in transgenic fish (21–26%) compared with non-transgenic fish (42.5%; P<0.001). Our results suggest that high growth rates per se are not sufficient to cause vaterite deposition in all cases, and that GH overexpression might have a protective role against vaterite deposition, a hypothesis that needs further investigation.