New party performance after breakthrough: Party origin, building and leadership

This is the author accepted manuscript. The final version is available from SAGE Publications via the DOI in this record.Parliamentary entry on the national level is a crucial achievement for any new party. But its repercussions are not necessarily beneficial. This article assesses the electoral consequences of parliamentary breakthrough by theorizing factors that shape (a) a new party organization’s capacity to cope with pressures generated by parliamentary entry and (b) the relative intensity of the new functional pressures a new party is exposed to after breakthrough. To test our hypotheses derived from these two rationales, we apply multilevel analyses to a new data set covering 135 organizationally new parties that entered national parliament across 17 advanced democracies over nearly five decades (1968–2015). Our findings stress the importance of party organizational characteristics (party origin, time for party building and leadership continuity) for parties’ capacity to sustain electoral support after breakthrough. In contrast, the intensity of functional pressures as generated by government participation immediately after breakthrough does not have significant effects on parties’ performance at the follow-up election.The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This research has received funding from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–13)/ERC grant agreement 335890 STATORG). This support is gratefully acknowledged

Biophysikalische Eigenschaften und Biotransformation metallbasierender Medikamente

Im Rahmen dieser Dissertation wurden Kapillarelektrophorese (CE) und induktiv gekoppeltes Plasma-Massenspektrometrie (ICP-MS) zur Untersuchung pharmakokinetischer Aspekte von metallbasierenden Krebsmedikamenten mit Ru und Pt als Zentralatom eingesetzt. Des Weiteren wurden beide Techniken zum ersten Mal zur Charakterisierung der Wechselwirkungen zwischen Antidiabetika und Serumproteinen verwendet. Die zelluläre Aufnahme ist ein wichtiger Faktor in der antineoplastischen Chemotherapie. Je lipophiler eine Verbindung ist, desto leichter kann sie passiv die Membran passieren und in der Zelle angereichert werden. Eine höhere Akkumulation des Chemotherapeutikums im Tumorgewebe resultiert oft in einer verbesserten Antiproliferation. Die Lipophilie für verschiedene Pt Verbindungen wurde sowohl mit der Shake-Flask Methode als auch indirekt mit elektrokinetischer Chromatographie mit Mikroemulsionen (MEEKC) bestimmt. Im Zuge dieser Untersuchungen wurde die Hybridtechnik MEEKC-ICP-MS etabliert. Diese neuartige Technik zeichnet sich durch ein niedriges Detektionslimit aus und ermöglicht auch die Kapazitätsfaktor (log k) Bestimmung von UV/vis-inaktiven Verbindungen. Eine gute Korrelation zwischen den log k Werten, die mit MEEKC bzw. MEEKC-ICP-MS bestimmt wurden, und den dazugehörigen Oktanol-Wasser-Verteilungskoeffizienten (log P) wurde bei Komplexen mit geringen strukturellen Unterschieden beobachtet. Zur Bestätigung der Struktur-Wirkungs-Beziehung wurden die log P und log k Werte in Korrelation mit der Akkumulation der Pt-Komplexe in verschiedenen Zelllinien und deren Zytotoxizität gebracht. Es zeigte sich, dass je lipophiler der Komplex ist desto größer ist die zelluläre Aufnahme und umso kleiner der IC50 Wert. Der Einfluss der Lipophilie auf die Verteilung von Oxaliplatin und dessen Methylderivaten KP1691 und KP1537 in tumortragenden Mäusen wurde ebenfalls untersucht. Die Analyse des Platingehaltes in verschiedenen Geweben zeigte, dass KP1691 zum einem sehr schnell im Tumor angereichert wird, aber auch sehr schnell wieder ausgeschieden wird. Zwischen Oxaliplatin und KP1537 wurden keine großen Unterschiede in der Tumorakkumulation im beobachteten Zeitraum festgestellt. Ein weiterer Schwerpunkt dieser Doktorarbeit war die Untersuchung der Wechselwirkung von therapeutischen Metallkomplexen mit Serumproteinen. Die Anbindung an Serumproteine hat einen entscheidenen Einfluss auf die Bioverteilung und den Wirkmechanismus von Arzneimitteln. Mit Hilfe der Hybridtechnik CZE-ICP-MS konnte gezeigt werden, dass Albumin den Hauptbindungspartner im Blut für den zur Zeit in klinischen Studien getesteten Ru-Komplex Natrium trans-[tetrachloridobis-(1H-indazol)ruthenat(III)] (KP1339) wie auch für Antidiabetika auf Zinkbasis darstellt. Die experimentellen Daten für die Zn-Komplexe Zusammenfassung bestätigten theoretische Berechnungen der Stabilitätskonstanten. Zusätzlich zu der Verteilung im Blut wurde für KP1339 die Akkumulation in diversen Mausorganen untersucht. Hohe Konzentrationen in Lunge und Thymus machen diese Verbindung möglicherweise interessant für die Behandlung von Lungenkrebs und lymphoblastischer Leukämie. Zusammenfassend kann gesagt werden, dass bioanalytische Methoden signifikant zu einem besseren Verständnis des Verhaltens und der Eigenschaften von neuen Medikamenten beitragen können. Dies wiederum ermöglicht die Entwicklung von Verbindungen mit definierten pharmakologischen Wirkungsmustern, die die Effektivität von Therapien verbessern und Nebenwirkungen minimieren könnten.Within this Ph.D. thesis, capillary electrophoresis (CE) and inductively coupled plasma mass spectrometry (ICP-MS) were applied to investigate the pharmacokinetic aspects of metalbased anticancer compounds with Ru or Pt as central atoms. Furthermore, both techniques were used for the first time to characterize the interaction between anti-diabetic complexes with serum proteins. An important factor in antineoplastic chemotherapy is the cellular uptake of drugs. The more lipophilic a compound is, the easier it can pass the membrane by passive diffusion and accumulate in the cell. A higher accumulation of the anticancer drug in the tumor tissue normally results in higher antitumor activity. The lipophilicity of a set of Pt compounds was determined by the shake-flask method as well as indirectly by microemulsion electrokinetic chromatography (MEEKC). During these investigations the hybrid technique MEEKC-ICPMS was established for the first time. This new method is characterized by a low detection limit and enables the determination of the capacity factor (log k) of UV/vis-silent compounds. A good correlation between log k obtained by MEEKC and MEEKC-ICP-MS and the corresponding octanol-water-partition coefficient (log P) was observable for complexes with minor structural differences. To confirm the structure-activity relationship, the log P and log k values were set in correlation with the accumulation of the Pt complexes in cancer cell lines and their cytotoxicity. It was found that the more lipophilic the compound is, the higher is the cellular uptake and the lower is the IC50 value. The influence of the lipophilicity on the biodistribution of oxaliplatin and its methyl derivatives KP1537 and KP1691 was also studied in tumor-bearing mice. The analysis of the Pt content in different tissue samples indicated that KP1691 is quickly accumulated in the tumor but also the efflux is rather rapid. No differences in the tumor accumulation were seen for oxaliplatin and KP1537 in a time frame of 6 h. A further focus of this thesis was the interaction of therapeutic metal complexes with serum proteins. The binding of drugs to serum proteins has a big impact on their biodistribution and modes of action. With the help of the hybrid technique CZE-ICP-MS, it was shown that albumin is the main binding partner for the Ru complex sodium trans-[tetrachloridobis-(1Hindazole)ruthenate(III)] (KP1339), currently undergoing clinical trials, as well as for Zn-based anti-diabetic compounds. The experimental data for the Zn complexes confirmed theoretical calculations based on stability constants. Additionally to the plasma distribution of KP1339, the accumulation in different tissues was investigated. High concentrations in lung and thymus make this compound interesting for the treatment of lung cancer and lymphoblastic leukemia. Concluding, bioanalytical methods can significantly contribute to a better understanding of the properties and biological behavior of novel remedies. This enables the development of compounds with defined pharmacological mechanism, which could improve treatment efficacy and reduce side effects

Online-Umfragen: eine geeignete Erhebungsmethode für die Wahlforschung? Ein Vergleich unterschiedlicher Befragungsmodi am Beispiel der Bundestagswahl 2009

"Online-Umfragen werden in den Sozialwissenschaften immer beliebter, so auch in der Wahlforschung. Zahlreiche Studien konnten jedoch zeigen, dass sich Teilnehmer/innen an Online-Umfragen nicht nur hinsichtlich des soziodemographischen Hintergrunds, sondern auch der politischen Einstellungen von Teilnehmer/innen an persönlich-mündlichen oder telefonischen Umfragen deutlich unterscheiden. Bei Analysen des Wählerverhaltens sind diese Unterschiede jedoch unproblematisch, wenn sich die Zusammenhänge zwischen den Untersuchungsmerkmalen im Rahmen der verschiedenen Befragungsmodi ähnlich gestalten und somit die Wahlentscheidung durch dieselben Faktoren erklärt werden kann. Der vorliegende Beitrag widmet sich der Betrachtung dieser Zusammenhänge, indem Modelle des Wahlverhaltens miteinander verglichen werden, die mit Daten verschiedener Umfragemodi berechnet wurden. Hierfür werden Daten der German Longitudinal Election Study (GLES) herangezogen, da im Rahmen dieses Projekts im Vorfeld der Bundestagswahl 2009 eine persönlich-mündliche, eine telefonische und mehrere Online-Umfragen nahezu zeitgleich durchgeführt wurden, was ideale Bedingungen für einen Vergleich der verschiedenen Umfragemodi bietet. Diese Untersuchung trägt somit dazu bei, die Eignung von Online-Umfragen für Analysen der empirischen Wahlforschung besser einschätzen zu können." (Autorenreferat)"Online surveys are becoming more and more popular in the social sciences, for example in electoral research. Plenty of studies have shown that participants who take part in online-surveys differ significantly from participants taking part in face-to-face, or telephone surveys, in terms of their socio-demographic background and political attitudes. Still, since electoral research aims primarily to explain voting behavior, online surveys are deemed useful tools, if the relationship between dependent and independent variables are similar in different survey types, for instance, if vote choice can be described by the same factors, regardless of the survey mode. This paper analyzes these relationships by comparing models of voting behavior which are based on data from different survey modes. Survey data from the German Longitudinal Election Study (GLES) is used since this project simultaneously conducted a face-to-face and telephone survey, as well as online surveys ahead of the 2009 German Federal Election. Hence, these are ideal conditions for comparing different survey modes. Consequently, this paper enables one to evaluate the use of online surveys for empirical electoral research." (author's abstract

Beyond Duverger: Party Ideology, Party-State Relations and Informal Finance Strategies in Advanced Democracies

publication-status: Acceptedtypes: ArticleThis is the accepted version of the following article: Beyond Duverger: party ideology, party-state relations and informal finance strategies in advanced democracies, which has been published in final form at http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=9157737This article examines one widespread but widely overlooked informal party practice to access state resources indirectly: the ‘taxing’ of MP salaries, which obliges candidates who win elected office on a party ticket to regularly donate a fixed share of their private income to party coffers. Linking Duverger’s classical approach on party organization that stresses the importance of party–society relations with the more recent, highly influential cartel party theory that argues that parties are shaped by their relationship with the state, we specify factors that shape the acceptability of this informal practice and thus parties’ capacity to extract rent from their MPs. The analysis of an original dataset covering parties across a wide range of advanced democracies reveals that demanding salary transfers from national MPs to their parties are not only more common in leftist parties as argued by Duverger but also in systems in which the penetration of the state apparatus by political parties is intense as argued by the cartel party approach. Linking the two perspectives further reveals that ideological differences between parties shape their relative capacity to collect higher payments from MPs in systems where parties and the state are less intertwined.British AcademyEconomic and Social Research Counci

The impact of whole human blood on the kinetic inertness of platinum(IV) prodrugs - an HPLC-ICP-MS study

The potential advantage of platinum(IV) complexes as alternative to classical platinum(II)-based drugs relies on their kinetic stability in the body before reaching the tumor site and on their activation by reduction inside cancer cells. In this study, an analytical workflow was developed to investigate the reductive biotransformation and kinetic inertness of platinum(IV) prodrugs comprising different ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of the platinum(IV) complexes in blood pellet and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion. An analytical approach based on reversed-phase (RP)-ICP-MS was used to monitor the parent compound and the formation of metabolites using two different extraction procedures. The ligand coordination sphere of the platinum(IV) complexes had significant impact on their accumulation in red blood cells and on their degree of kinetic inertness in whole human blood. The most lipophilic platinum(IV) compound featuring equatorial chlorido ligands showed a pronounced penetration into blood cells and a rapid reductive biotransformation. In contrast, the more hydrophilic platinum(IV) complexes with a carboplatin- and oxaliplatin-core exerted kinetic inertness on a pharmacologically relevant time scale with notable amounts of the compound accumulated in the plasma fraction

Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration-UV-vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K (1)' = 5.3-5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event