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The ability to hold MPs accountable for their actions is one of the cornerstones of modern representative democracy. While it is important for MPs to send signals to both their constituents and to their party, a large number of MPs remain absent from votes. Those absences are an important part of the MP’s toolbox, but absences carry limitations, rooted in electoral and political constraints. We investigate how—conditional on the electoral cycle—some well-established political constraints along the government and opposition lines vary in strength. We examine the absence probabilities of MPs in the United Kingdom from 1997 to 2015, and find that as the next elections are approaching, political constraints somewhat weaken and electoral ones take over, but marked differences emerge between parliamentary sessions.

BackgroundAnimal protein production is increasingly looking towards microbiome associated services such as the design of new and better probiotic solutions to further improve gut health and production sustainability. Here, we investigate the functional effects of bacteria based pro- and synbiotic feed additives on microbiome associated functions in relation to growth performance in the commercially important rainbow trout (Oncorhynchus mykiss). We combine complementary insights from multiple omics datasets from gut content samples, including 16S bacterial profiling, whole metagenomes, and untargeted metabolomics, to investigate bacterial metagenomic assembled genomes (MAGs) and their molecular interactions with host metabolism.ResultsOur findings reveal, that (I) feed additives changed the microbiome and that rainbow trout reared with feed additives had a significantly reduced relative abundance of the salmonid related Candidatus Mycoplasma salmoninae in both the mid and distal gut content, (II) genome resolved metagenomics revealed that alterations of microbial arginine biosynthesis and terpenoid backbone synthesis pathways were directly associated with presence of Candidatus Mycoplasma salmoninae, (III) differences in the composition of intestinal microbiota among feed types were directly associated with significant changes of the metabolomic landscape, including lipids and lipid-like metabolites, amino acids, bile acids, and steroid-related metabolites.ConclusionOur results demonstrate how use of multi-omics to investigate complex host-microbiome interactions enable us to better evaluate the functional potential of probiotics compared to studies that only measure overall growth performance or that only characterise the microbial composition in intestinal environments.

© 2020 The Author(s). Voters use various cues to make their decision. We examine the impact of the cue of candidate position on Brexit. Brexit is still on the agenda and we explore how this topic continues to divide the electorate. We test this by assessing the general preference of candidates among respondents in a series of surveys providing variation in the information regarding candidates’ positions on Brexit and party identification. In contrast to existing literature, we find strong evidence that candidates can utilise either their own previous voting behaviour or that of their opponent to provide an electoral advantage. Leave supporting candidates are highly rated by leave voters and poorly rated by remain voters, and vice versa for remain candidates, although it is dependent on the party label of the candidate. The issue of Brexit has a strong impact, but partisanship is mostly of equal importance for the respondents.

Understanding how MPs use ties to their constituency, or localness, is important for understanding the nature of the MP-constituency relationship. MPs are expected to actively focus on their consti...

Plastic pollution has become a major concern on a global scale. The plastic is broken down into minuscule particles, which have an impact on the biosystems, however long-term impacts through an entire generation is largely unknown. Here, we present the first whole generation study exposing fish to a 500 nm polystyrene plastic particle at environmentally relevant concentrations. Short- and long-term adverse effects were investigated in the zebrafish model organism using a holistic multi-omics approach. The particles accumulated in the yolk sac of young larvae and short-term biological impacts included immune-relevant gene regulation related to inflammation and tolerance as well as disruption of metabolic processes, such as the fatty acid and lipid pathways. The long-term effects comprised gene regulations pointing towards skin and/or gill inflammation, dysbiosis of the gut microbiota, a tendency towards decreased condition factor in adult males as well as a lowered reproductive capability. From this study, it can be concluded that exposures to plastic nanoparticles have an impact on population as well as ecosystem level in fish and likely also in other vertebrates.

Non-target analysis (NTA) employing high-resolution mass spectrometry is a commonly applied approach for the detection of novel chemicals of emerging concern in complex environmental samples. NTA typically results in large and information-rich datasets that require computer aided (ideally automated) strategies for their processing and interpretation. Such strategies do however raise the challenge of reproducibility between and within different processing workflows. An effective strategy to mitigate such problems is the implementation of inter-laboratory studies (ILS) with the aim to evaluate different workflows and agree on harmonized/standardized quality control procedures. Here we present the data generated during such an ILS. This study was organized through the Norman Network and included 21 participants from 11 countries. A set of samples based on the passive sampling of drinking water pre and post treatment was shipped to all the participating laboratories for analysis, using one pre-defined method and one locally (i.e. in-house) developed method. The data generated represents a valuable resource (i.e. benchmark) for future developments of algorithms and workflows for NTA experiments., Measurement(s)chemical • drinking waterTechnology Type(s)high resolution mass spectrometry • non-target analysis • InterlaboratoryFactor Type(s)methodSample Characteristic - Environmentlaboratory environment Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.15028665

Background Animal protein production is increasingly looking towards microbiome associated services such as the design of new and better probiotic solutions to further improve gut health and production sustainability. Here, we investigate the functional effects of bacteria based pro- and synbiotic feed additives on microbiome associated functions in relation to growth performance in the commercially important rainbow trout (Oncorhynchus mykiss). We combine complementary insights from multiple omics datasets from gut content samples, including 16S bacterial profiling, whole metagenomes, and untargeted metabolomics, to investigate bacterial metagenomic assembled genomes (MAGs) and their molecular interactions with host metabolism. Results Our findings reveal, that (I) feed additives changed the microbiome and that rainbow trout reared with feed additives had a significantly reduced relative abundance of the salmonid related Candidatus Mycoplasma salmoninae in both the mid and distal gut content, (II) genome resolved metagenomics revealed that alterations of microbial arginine biosynthesis and terpenoid backbone synthesis pathways were directly associated with presence of Candidatus Mycoplasma salmoninae, (III) differences in the composition of intestinal microbiota among feed types were directly associated with significant changes of the metabolomic landscape, including lipids and lipid-like metabolites, amino acids, bile acids, and steroid-related metabolites, (IV) performance data of pro- and synbiotic additives indicates alterations of protein and lipid efficiency ratios in rainbow trout. Conclusion Our results demonstrate how use of multi-omics to investigate complex host-microbiome interactions enable us to better evaluate the functional potential of probiotics compared to studies that only measure overall growth performance or that only characterise the microbial composition in intestinal environments.

We present a non-perturbative lattice calculation of the form factors which contribute to the amplitudes for the radiative decays $P\to \ell \bar \nu_\ell \gamma$, where $P$ is a pseudoscalar meson and $\ell$ is a charged lepton. Together with the non-perturbative determination of the corrections to the processes $P\to \ell \bar \nu_\ell$ due to the exchange of a virtual photon, this allows accurate predictions at $O(\alpha_{em})$ to be made for leptonic decay rates for pseudoscalar mesons ranging from the pion to the $D_s$ meson. We are able to separate unambiguously and non-pertubatively the point-like contribution, from the structure-dependent, infrared-safe, terms in the amplitude. The fully non-perturbative $O(a)$ improved calculation of the inclusive leptonic decay rates will lead to the determination of the corresponding Cabibbo-Kobayashi-Maskawa (CKM) matrix elements also at $O(\alpha_{em})$. Prospects for a precise evaluation of leptonic decay rates with emission of a hard photon are also very interesting, especially for the decays of heavy $D$ and $B$ mesons for which currently only model-dependent predictions are available to compare with existing experimental data., Comment: 46 pages, 12 figures

The formation of Danish governments and their governance continues to be of interest both on their own and comparatively. Minority coalition governments are the norm in Denmark, increasing the importance of support parties for the government to pass its policies. Danish politics can increasingly be seen as two blocs: the ‘red’ bloc led by the Social Democrats and the ‘blue’ bloc led by the Liberals (although it was the Conservatives in the 1980s). This division may have increased the tendency of the presidentialization of Danish politics, not least with the prime minister’s increasing engagement in the day-to-day running of the government, especially with regard to foreign policy. Similarly, the minister of finance is ever more important as well for the day-to-day running of other departments. Ministerial turnover through reshuffles happens during the tenure of most governments, but portfolio redesign mostly occurs when governments are formed. The distribution of portfolios is proportional, but there is much variation in which portfolios parties prefer, with some valuing importance over number of portfolios. Overall, the Danish government and prime minister is a well-researched area, although there is still significant scope for research innovation.

Understanding why people visit museums is of interest to both cultural economics and museum studies. Most existing research relies on survey data concerned with visitors, their immediate background, and their experience of a particular museum. Very few studies (e.g. Chen & Della Change, 2016; Skinner et al., 2009) have taken a more general perspective and analysed macro-level societal factors, such as inflation, educational attainment and unemployment, and their influence on the number of visits to museums. The conventional approach being reliance on surveys of museum visitors used to understand what drives visits and general views on museums. In a departure from these conventional approaches, this article presents such an approach, using a unique dataset of visit counts for 40 English museums and visitor attractions spanning the period 1850-2015, unless otherwise specified the word “museum” shall in this article cover both types It examines the effect of socio-economic factors on visits using panel data analysis and macro-level variables. The results suggest that inflation rates, average earnings, and educational level (using the indicator of secondary school attendance) all significantly influence the number of visits made. However, the most important variable is the number of visits recorded for the previous year. These findings are discussed in relation to existing studies, and some suggestions for future research are proposed.

We present a non-perturbative calculation of the form factors which contribute to the amplitudes for the radiative decays $P\to \ell \bar \nu_\ell \gamma$, where $P$ is a pseudoscalar meson and $\ell$ is a charged lepton. Together with the non-perturbative determination of the virtual photon corrections to the processes $P\to \ell \bar \nu_\ell$, this will allow accurate predictions to be made at $O(\alpha_{em})$ for leptonic decay rates for pseudoscalar mesons ranging from the pion to the $B$ meson. We are able to separate unambiguously the point-like contribution, the square of which leads to the infrared divergence in the decay rate, from the structure dependent, infrared-safe, terms in the amplitude. The fully non-perturbative, $O(a)$ improved calculation of the inclusive leptonic decay rates will lead to significantly improved precision in the determination of the corresponding Cabibbo-Kobayashi-Maskawa (CKM) matrix elements. Precise predictions for the emission of a hard photon are also very interesting, especially for the decays of heavy $D$ and $B$ mesons for which currently only model-dependent predictions are available to compare with existing experimental data.

The design of government portfolios – that is, the distribution of competencies among government ministries and office holders – has been largely ignored in the study of executive and coalition politics. This article argues that portfolio design is a substantively and theoretically relevant phenomenon that has major implications for the study of institutional design and coalition politics. The authors use comparative data on portfolio design reforms in nine Western European countries since the 1970s to demonstrate how the design of government portfolios changes over time. Specifically, they show that portfolios are changed frequently (on average about once a year) and that such shifts are more likely after changes in the prime ministership or the party composition of the government. These findings suggest a political logic behind these reforms based on the preferences and power of political parties and politicians. They have major implications for the study of institutional design and coalition politics.

Hadronic spectral densities are important quantities whose nonperturbative knowledge allows for calculating phenomenologically relevant observables, such as inclusive hadronic cross sections and nonleptonic decay rates. The extraction of spectral densities from lattice correlators is a notoriously difficult problem because lattice simulations are performed in Euclidean time and lattice data are unavoidably affected by statistical and systematic uncertainties. In this paper we present a new method for extracting hadronic spectral densities from lattice correlators. The method allows for choosing a smearing function at the beginning of the procedure and it provides results for the spectral densities smeared with this function together with reliable estimates of the associated uncertainties. The same smearing function can be used in the analysis of correlators obtained on different volumes, such that the infinite-volume limit can be studied in a consistent way. While the method is described by using the language of lattice simulations, in reality it is completely general and can profitably be used to cope with inverse problems arising in different fields of research.

In his recent article, Söderlund [Söderlund, P.J., 2003. The significance of structural power resources in the Russian bi-lateral treaty process 1994–1998. Communist and Post-Communist Studies 36, 311–324] tests structural factors that influence the order in which the Russian regions gained a bi-lateral agreement with the federal centre, emphasizing the importance of ethnicity, religion and economy. We replicate his results, and provide an extension where we argue instead that the only significant determinants of the bi-lateral process have been economic issues. Our results are substantiated by an improved methodology that addresses several debatable choices made by the author in the original article.

In nearly all studies on legislative party competition, all votes are treated equally. It is argued in this article that the cooperation between parties varies substantively depending on the type of legislation analysed. However, establishing a measure of the relative significance of votes has challenged legislative studies for decades. A novel measure for legislative significance is therefore proposed: length of debate. Using parliamentary votes from 23 legislative periods in the Danish parliament from 1953 to 2003 and debate length as measurement for bill significance, analyses are presented that focus on between-party voting patterns on significant and non-significant legislation and the presence, extent and features of legislative cartels is discussed. The results suggest that looking only at significant legislation reveals more clearly the legislative cartels within the legislature. These findings challenge the traditional assumption of treating parliamentary votes equally, and they allow for a better understanding of legislative cartels in the Folketing.

This is the post-print version of the article which has been accepted for publication and will appear in a revised form, subsequent to peer review and/or editorial input in Politics and Gender. Copyright @ Cambridge University Press.

Previous studies have found that Austria has one of the most nationalized party systems in Western Europe. Using local election data from over 2300 municipalities between 1985 and 2009, we show that nationalisation of the party system varies considerably across regions. We demonstrate that variation in the organisational strength of regional party branches accounts for this finding, even when controlling for municipality size and the time dimension.

The study of committee assignment politics is very limited in parliamentary systems. Even more limited is the study of the change in committee assignments that occurs between elections. In this article, a first attempt to rectify this, both theoretically and empirically, is presented. What might have an impact on committee reassignments and what relationship one would expect to find are discussed. Using data of all Danish committee assignments 1994–2007, the proposed relationships are tested. The results show that: (1) it varies which parties experience the more change; and (2) it is often related to internal problems, but vote share, seniority and whether an MP is involved in a ministerial reshuffle or not also have a significant influence on change of committee assignments.

Parties are usually seen as unitary and cohesive bodies. In this article we explore the extent to which this is the case also among party candidates. Using candidates' answers to policy questions from voting advice applications from the 2011 Danish general election we find that while it depends both on the party and on the policy issue generally parties are incohesive.

© The Author(s) 2018. This article presents an argument for committee assignments based not in the traditional congressional theories, but on elements central to parliamentary systems: government formation. The argument of the article is that it is necessary to include the link between committees and cabinet governance for understanding parliamentary committees. This is tested on 40 years of committee assignments from the Danish parliament. The findings suggest that an approach inspired by a classic portfolio allocation model works best in explaining the distribution of seats and chairs between parties. Shadowing of coalition partners appears to matter little, if at all.

Committees are the backbone of any modern legislature. Membership of committees is in most parliaments a gift within the reach of the party groups. Yet, both theoretically and empirically, little is known about committee allocation in parliaments. Using theories from the literature of the US Congress, a framework for analysis of the committee assignments in Dail Eireann is presented. Empirically, the contribution of this paper is twofold. First, it analyzes what factors influence the allocation of Teachta Dalas (TDs) to Dail committees. Second, it analyzes to what extent the participation of TDs in committee changes over time. The former analysis corroborates results found in other parliaments; few factors seem to have an influence. The latter analysis confirms that the participation of TDs changes over time and seems to be tied in with the changing scope and influence of the committee system. The analyzes rely on a data set consisting of all committee assignments in the Dail since November 1982 until Jun...

This paper deals with how minor parties and independents act once they have won election to the parliament. Using a dataset of all votes in Dail Eireann from 1937 to 2007 the rate of agreement with Fianna Fail, Fine Gael and Labour for each independent and minor party candidate is calculated. Based on theories of the behaviour of parties and independents a number of hypotheses are formulated and tested. The conclusions of the paper are that minor parties are very likely to vote against the government when they are not a part of it and that for independents the particular typology matters. When independents are needed by the government, not only those independents needed but the entire body of independents are significantly more in agreement with the government than when they are not needed.

Committees are the backbone of nearly every modern legislature. Yet there is relatively little knowledge about how committee assignment politics occur in the multiparty parliaments with minority coalition governments that so often are the case in many European countries. Is there a pattern to which MPs are assigned to which committees? In this article the Danish case is used to address this question. A dataset of all committee assignments in the Danish Folketing from the period 1994–2007 has been collected; added to this are data on each MP. The data are analysed using a quantitative approach, and drawing on the literature on committee assignments in the United States Congress and the European Parliament, complementing the vast qualitative studies, and updating the few quantitative studies, of the Danish parliamentary committees. The results show that which variables have an influence on committee assignments varies across parties and that no uniform pattern is found.

Auf der Grundlage einer Analyse der namentlichen Abstimmungen im Reichstag der Weimarer Republik werden dessen Dimensionalitat sowie die Positionierung der einzelnen Abgeordneten auf den ermittelten Dimensionen zwischen 1920 und 1932 analysiert. Basierend auf bisherigen Arbeiten zur Milieugebundenheit der Parteien der Weimarer Republik sowie theoretischen Ansatzen zur Dimensionalitat des Abstimmungsverhaltens in Parlamenten werden Erwartungen hinsichtlich der Anzahl sowie der inhaltlichen Beschaffenheit der Konfliktlinien innerhalb des Parlaments aufgestellt, die dann in einer Analyse der namentlichen Abstimmungen, die auf Item-response-Modellen aufbaut, getestet werden. Die Ergebnisse zeigen, dass zwei Dimensionen das Abstimmungsverhalten dominiert haben: Dies ist der von wirtschafts- und sozialpolitischen Fragen determinierte Links-Rechts-Konflikt einerseits sowie der Gegensatz zwischen Befurwortern und Gegnern der parlamentarisch-republikanischen Ordnung andererseits. Zudem konnen aktuelle zeithistorische Arbeiten, die einen Konflikt innerhalb der Deutschnationalen Volkspartei thematisieren, auf der Grundlage der Positionen einzelner Abgeordneter dieser Partei bestatigt werden.

Ireland is often described as the odd country out in studies of west European politics. Its parties do not readily fit into the classical European definitions of party families. This paper estimates the positions of the parliamentary parties since 1937, based on a dataset consisting of all parliamentary votes from 1937 to 2006 using a Bayesian ideal point estimation framework. It is shown that party competition in the Irish parliament adheres to a government‐opposition dimension, and that it is possible to distinguish only two blocs of parties in each period, one consisting of the parties supporting the government and one comprising the remaining parties as the opposition. It is argued that the estimated positions do not reflect party policy positions but are instead voting cohesion of two distinct blocs of the parliamentary parties. The findings are validated by a comparison with various expert surveys of Irish party positions.

Using the index of distances and the Optimal Classification method, the party positions and the dimensionality of the Danish Folketing is calculated from 1920 to 2005. The empirical results suggest that a one-dimensional model explains around 85 per cent of the legislative dimensionality in Denmark over time with only a modest presence of two or more dimensions in the 1970s. The rank order of party positions derived through the index of distance has higher face validity than the rankings derived through the Optimal Classification method. The Optimal Classification method produces a dimensionality measure which, when analysed, can be used to explain most of the events in Danish politics over the last 80 years. It is further argued that the shifts in the dimensionality can be explained by the number of parties in parliament and by historical incidents.

Copyright @ 2008 The authors. This is the accepted version of the following article: Hansen, M. E. (2008), Back to the Archives? A Critique of the Danish Part of the Manifesto Dataset. Scandinavian Political Studies, 31: 201–216, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1467-9477.2008.00202.x/abstract. The dataset of the Comparative Manifesto Project (CMP) is one the best known and often used datasets in comparative studies of Western Europe. However, the Danish part of the data is very problematic. On average, nearly a third of the content of the Danish manifestos is deemed impossible to code. A close examination of the Danish data reveals large variations in the number of coded sentences across time and parties. An analysis of the manifestos on which the coding is based sets all the warning lights flashing. First, not all manifestos are in fact manifestos; a number consist of other political texts (i.e. speeches, drafts) or even stem from different elections (e.g. municipal manifestos masquerading as national manifestos). Second, the large variation in the length of the manifestos across time suggests that the information derived from them is not readily comparable. This leads to a distorted picture of the positions of the Danish parties. The conclusion of this article is that in order for the Danish part of the CMP dataset to become more trustworthy, it is necessary to search the archives, find the actual manifestos and recode them.

We investigate the continuum spectrum of the SU(2) gauge theory with $N_f=2$ flavours of fermions in the fundamental representation. This model provides a minimal template which is ideal for a wide class of Standard Model extensions featuring novel strong dynamics that range from composite (Goldstone) Higgs theories to several intriguing types of dark matter candidates, such as the SIMPs. We improve our previous lattice analysis [1] by adding more data at light quark masses, at two additional lattice spacings, by determining the lattice cutoff via a Wilson flow measure of the $w_0$ parameter, and by measuring the relevant renormalisation constants non-perturbatively in the RI'-MOM scheme. Our results for the lightest isovector states in the vector and axial channels, in units of the pseudoscalar decay constant, are $m_V/F_{\rm{PS}}\sim 13.1(2.2)$ and $m_A/F_{\rm{PS}}\sim 14.5(3.6)$ (combining statistical and systematic errors). In the context of the composite (Goldstone) Higgs models, our result for the spin-one resonances are $m_V > 3.2(5)$ TeV and $m_A > 3.6(9)$ TeV, which are above the current LHC constraints. In the context of dark matter models, for the SIMP case our results indicate the occurrence of a compressed spectrum at the required large dark pion mass, which implies the need to include the effects of spin-one resonances in phenomenological estimates., 35 pages, 18 figures

We augment the chiral Lagrangian by an isosinglet scalar and compute the one-loop radiative corrections to the pion mass and decay constant, as well as the scalar mass. The calculations are carried out for different patterns of chiral symmetry breaking of immediate relevance for phenomenology and lattice investigations. By construction our results encompass several interesting limits, ranging from the dilaton to the linear sigma model., Comment: 18 pages, 2 figures, accepted version for Physical Review D

This paper evaluates a recently developed method for extracting policy positions from political texts, known as Wordscores. This computerized content analysis technique is a potentially powerful tool for scholars interested in the study of political elites, since it promises an easy and efficient way of inferring policy position from texts and speeches. In this article, we provide a systematic evaluation of this promising method. Using Danish manifestos and government speeches from 1945 to 2005, we compare the policy positions extracted using Wordscores with measures of positions from the well-known Comparative Manifesto Project and cross-validate these with party expert surveys. Our analysis shows that the word scoring technique arrives at largely similar estimates to independently derived position measures and produces time series of government positions with high face validity.

Latency transition of plasminogen activator inhibitor-1 (PAI-1) occurs spontaneously in the absence of proteases and results in stabilization of the molecule through insertion of its reactive center loop (RCL) as a strand in beta-sheet A and detachment of beta-strand 1C (s1C) at the C-terminal hinge of the RCL. This is one of the largest structural rearrangements known for a folded protein domain without a concomitant change in covalent structure. Yet, the sequence of conformational changes during latency transition remains largely unknown. We have now mapped the epitope for the monoclonal antibody H4B3 to the cleft revealed upon s1C detachment and shown that H4B3 inactivates recombinant PAI-1 in a time-dependent manner. With fluorescence spectroscopy, we show that insertion of the RCL is accelerated in the presence of H4B3, demonstrating that the loss of activity is the result of latency transition. Considering that the epitope for H4B3 appears to be occluded by s1C in active PAI-1, this finding suggests the existence of a pre-latent conformation on the path from active to latent PAI-1 characterized by at least partial detachment of s1C. Functional characterization of mutated PAI-1 variants suggests that a salt-bridge between Arg273 and Asp224 may stabilize the pre-latent conformation. The binding of H4B3 and of a peptide targeting the cleft revealed upon s1C detachment was hindered by the glycans attached to Asn267. Conclusively, we have provided evidence for the existence of an equilibrium between active PAI-1 and a pre-latent form, characterized by reversible detachment of s1C and formation of a glycan-shielded cleft in the molecule.

To find new principles for inhibiting serine proteases, we screened phage-displayed random peptide repertoires with urokinase-type plasminogen activator (uPA) as the target. The most frequent of the isolated phage clones contained the disulfide bridge-constrained sequence CSWRGLENHRMC, which we designated upain-1. When expressed recombinantly with a protein fusion partner, upain-1 inhibited the enzymatic activity of uPA competitively with a temperature and pH-dependent K(i), which at 25 degrees C and pH 7.4 was approximately 500 nm. At the same conditions, the equilibrium dissociation constant K(D), monitored by displacement of p-aminobenzamidine from the specificity pocket of uPA, was approximately 400 nm. By an inhibitory screen against other serine proteases, including trypsin, upain-1 was found to be highly selective for uPA. The cyclical structure of upain-1 was indispensable for uPA binding. Alanine-scanning mutagenesis identified Arg(4) of upain-1 as the P(1) residue and indicated an extended binding interaction including the specificity pocket and the 37-, 60-, and 97-loops of uPA and the P(1), P(2), P(3)', P(4)', and the P(5)' residues of upain-1. Substitution with alanine of the P(2) residue, Trp(3), converted upain-1 into a distinct, although poor, uPA substrate. Upain-1 represents a new type of uPA inhibitor that achieves selectivity by targeting uPA-specific surface loops. Most likely, the inhibitory activity depends on its cyclical structure and the unusual P(2) residue preventing the scissile bond from assuming a tetrahedral geometry and thus from undergoing hydrolysis. Peptide-derived inhibitors such as upain-1 may provide novel mechanistic information about enzyme-inhibitor interactions and alternative methodologies for designing effective protease inhibitors.

SummaryIn recent decades, evidence has been accumulating showing the important role of urokinase-type plasminogen activator (uPA) in growth, invasion, and metastasis of malignant tumours. The evidence comes from results with animal tumour models and from the observation that a high level of uPA in human tumours is associated with a poor patient prognosis. It therefore initially came as a surprise that a high tumour level of the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) is also associated with a poor prognosis, the PAI-1 level in fact being one of the most informative biochemical prognostic markers. We review here recent investigations into the possible tumour biological role of PAI-1, performed by animal tumour models, histological examination of human tumours, and new knowledge about the molecular interactions of PAI-1 possibly underlying its tumour biological functions. The exact tumour biological functions of PAI-1 remain uncertain but PAI-1 seems to be multifunctional as PAI-1 is expressed by multiple cell types and has multiple molecular interactions. The potential utilisation of PAI-1 as a target for anti-cancer therapy depends on further mapping of these functions.

Plasminogen activator inhibitor-1 (PAI-1) belongs to the serpin family of serine proteinase inhibitors. Serpins inhibit their target proteinases by an ester bond being formed between the active site serine of the proteinase and the P1 residue of the reactive centre loop (RCL) of the serpin, followed by insertion of the RCL into beta-sheet A of the serpin. Concomitantly, there are conformational changes in the flexible joint region lateral to beta-sheet A. We have now, by site-directed mutagenesis, mapped the epitope for a monoclonal antibody, which protects the inhibitory activity of PAI-1 against inactivation by a variety of agents acting on beta-sheet A and the flexible joint region. Curiously, the epitope is localized in alpha-helix C and the loop connecting alpha-helix I and beta-strand 5A, on the side of PAI-1 opposite to beta-sheet A and distantly from the flexible joint region. By a combination of site-directed mutagenesis and antibody protection against an inactivating organochemical ligand, we were able to identify a residue involved in conferring the antibody-induced conformational change from the epitope to the rest of the molecule. We have thus provided evidence for communication between secondary structural elements not previously known to interact in serpins.

The serpins are of general protein chemical interest due to their ability to undergo a large conformational change consisting of the insertion of the reactive centre loop (RCL), which becomes strand 4, into the central β sheet A. To make space for the incoming RCL, the ‘shutter region’ opens by the β strands 3A and 5A sliding apart over the underlying α helix B. Loop insertion occurs during the formation of complexes of serpins with their target serine proteinases and during latency transition. This type of loop insertion is unique to plasminogen activator inhibitor-1 (PAI-1). We report here that amino-acid substitutions in a buried cluster of three residues forming a hydrogen bonding network in the shutter region drastically accelerate PAI-1 latency transition; that the rate was in all cases normalized by the PAI-1 binding protein vitronectin; and that substitution of an adjacent β strand 5A Lys residue, believed to anchor β strand 5A to other secondary structural elements, had differential effects on the rates of latency transition in the absence and the presence of vitronectin, respectively. An overlapping, but not identical set of substitutions resulted in an increased tendency to substrate behaviour of PAI-1 at reaction with its target proteinases. These findings show that vitronectin regulates the movements of the RCL through conformational changes of the shutter region and β strand 5A, are in agreement with RCL insertion proceeding by different routes during latency transition and complex formation, and contribute to the biochemical basis for the potential use of PAI-1 as a therapeutic target in cancer and cardiovascular diseases.

© 2013 The Author(s) Scandinavian Political Studies © 2013 Nordic Political Science Association. This is the accepted version of the following article: Hansen, M. E., Klemmensen, R., Hobolt, S. B. and Bäck, H. (2013), Portfolio Saliency and Ministerial Turnover: Dynamics in Scandinavian Postwar Cabinets. Scandinavian Political Studies, 36: 227–248, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/1467-9477.12004/abstract. Why do certain ministers remain in their post for years while others have their time in office cut short? Drawing on the broader literature on portfolio allocation, this article argues that the saliency of individual portfolios shapes ministerial turnover. The main argument is that ministerial dismissals are less likely to occur the higher the saliency attributed to the ministerial portfolio since ministers appointed to important posts are more likely to have been through extensive screening before appointment. Importantly, it is also posited in the article that the effect of portfolio salience is conditioned by government approval ratings: when government ratings are on the decline, prime ministers are less likely to reshuffle or fire important ministers than when approval ratings are improving. To test these claims, Cox proportional hazards models are applied to a new dataset on ministerial turnover in Scandinavia during the postwar period. The results strongly support the proposition that portfolio saliency matters for ministerial survival, and that this effect is moderated by government popularity.

Copyright @ 2012 The Authors. This is the author's accepted manuscript. The final published article is available from the link below. Analysing the roll-call votes of the MPs of the Weimar Republic we find: (1) that party competition in the Weimar parliaments can be structured along two dimensions: an economic left–right and a pro-/anti-democratic. Remarkably, this is stable throughout the entire lifespan of the Republic and not just in the later years and despite the varying content of votes across the lifespan of the Republic, and (2) that nearly all parties were troubled by intra-party divisions, though, in particular, the national socialists and communists became homogeneous in the final years of the Republic. Zukunftskolleg, University of Konstanz

Studying candidate selection procedures and the list orderings are important for understanding all dynamics in play in electoral systems using lists with some sort of party selected ordering. Using data from Danish local elections how political parties select and order candidates for the party list, and how this ordering fares at the election is analyzed. Overall, party members have a say in who is selected and in which order. Which candidates are elected depends primarily on whether the party runs an open or a flexible list. If a flexible list is chosen the party ordering is almost perfectly followed in the order of candidates elected, whereas an open list produces very mixed results.

The serine proteinase inhibitor plasminogen activator inhibitor type-1 (PAI-1) is the primary physiological inhibitor of the tissue-type and the urokinase-type plasminogen activator (tPA and uPA, respectively) and as such an important regulator of proteolytic events taking place in the circulation and in the extracellular matrix. Moreover, a few non-proteolytic functions have been ascribed to PAI-1, mediated by its interaction with vitronectin or the interaction between the uPA-PAI-1 complex bound to the uPA receptor and members of the low density lipoprotein receptor family. PAI-1 belongs to the serpin family, characterised by an unusual conformational flexibility, which governs its molecular interactions. In this review we describe the anti-proteolytic and non-proteolytic functions of PAI-1 from both a biological and a biochemical point of view. We will relate the various biological roles of PAI-1 to its biochemistry in general and to the different conformations of PAI-1 in particular. We put emphasis on the intramolecular rearrangements of PAI-1 that are required for its antiproteolytic as well as its non-proteolytic functions.

We present new results from our ongoing study of the SU(3) sextet model with two flavors in the two-index symmetric representation of the gauge group. In the simulations use unimproved Wilson fermions to investigate the infrared properties of the model. We have previously presented results for the spectrum of the model in the weak coupling regime. Here, to better understand the overall behavior of the lattice model, we map its non-trivial phase structure in the space of bare parameters. At strong coupling, we observe a first order phase transition when decreasing the bare quark mass. This first order transition weakens when moving towards weaker couplings with an endpoint at a finite value of the bare coupling, after which it appears to be a continuous transition. We also investigate the behavior of the mass spectrum and scale-setting observable, as a function of the quark mass, and show that their qualitative behavior change significantly when moving from the strong coupling into the weak coupling phase., 7 pages, 6 figures, Contribution to the 34th International Symposium on Lattice Field Theory, 24-30 July 2016, University of Southampton, UK. Corrected plot in Fig. 6