How unstable? Volatility and the genuinely new parties in Eastern Europe

Measuring of party system stability in Eastern Europe during the first decade of democratic elections presents problems. The traditional quantitative measure - volatility - does not distinguish between the dynamics among incumbent parties and the rise of genuinely new ones. I propose a new additional measure - success of genuinely new parties - and compare it to volatility. The subsequent performance of initially successful genuinely new parties is analysed. While volatility has been remarkably high in East European countries, the genuinely new parties have, in general, not been very successful. Instability of party systems in the region stems rather from the inner dynamics of incumbent actors than from the rise of new contenders

Multi-parameter optimization: Development of a morpholin-3-one derivative with an improved kinetic profile for imaging monoacylglycerol lipase in the brain

Monoacylglycerol lipase (MAGL) is a gatekeeper in regulating endocannabinoid signaling and has gained sub-stantial attention as a therapeutic target for neurological disorders. We recently discovered a morpholin-3-one derivative as a novel scaffold for imaging MAGL via positron emission tomography (PET). However, its slow kinetics in vivo hampered the application. In this study, structural optimization was conducted and eleven novel MAGL inhibitors were designed and synthesized. Based on the results from MAGL inhibitory potency, in vitro metabolic stability and surface plasmon resonance assays, we identified compound 7 as a potential MAGL PET tracer candidate. [11C]7 was synthesized via direct 11CO2 fixation method and successfully mapped MAGL dis-tribution patterns on rodent brains in in vitro autoradiography. PET studies in mice using [11C]7 demonstrated its improved kinetic profile compared to the lead structure. Its high specificity in vivo was proved by using MAGL KO mice. Although further studies confirmed that [11C]7 is a P-glycoprotein (P-gp) substrate in mice, its low P-gp efflux ratio on cells transfected with human protein suggests that it should not be an issue for the clinical translation of [11C]7 as a novel reversible MAGL PET tracer in human subjects. Overall, [11C]7 ([11C] RO7284390) showed promising results warranting further clinical evaluation.Molecular Physiolog

The evolution of cleavage voting in four Western countries: Structural, behavioural or political dealignment?

Since the heyday of cleavage voting in the 1960s and 1970s, the majority of studies presents evidence of a decline in cleavage voting – caused by either structural or behavioural dealignment. Structural dealignment denotes changes in group size responsible for a decrease in cleavage voting, whereas behavioural dealignment concerns weakening party–voter links over time. A third phenomenon posited in this article is the collective voting abstention of certain (social) groups, here referred to as ‘political dealignment’, which results in a new type of division of voting versus abstention. The purpose of this article is to examine the three underlying mechanisms for the decline in social class and religious cleavage voting across four Western countries (Great Britain, the Netherlands, Switzerland and the United States) over the last 40–60 years using longitudinal post‐election data. The results prove a strong presence of political dealignment and increasing turnout gaps regarding both the class and religious cleavage. Furthermore, whenever a decline in cleavage voting is present, it is mainly caused by changes in the social groups’ behaviour and less by changing social structures in a country