Suchergebnisse

Elections differ not only between, but also within, countries. Some elections have very simple voting rules and ballots. For instance, in the parliamentary elections in Estonia or Germany, voters can select 1-out-of-n candidates. Other elections, like parliamentary elections in Luxembourg and Belgium or local elections in Germany, have very complex voting rules and huge ballots. These elections combine different voting rules, namely select k-out-of-n, weight and rank candidates, and therefore pose a challenge to both voters and electoral officials. Hence, in such elections voters are likely to spoil their vote unintentionally, due to the complex voting rules. In addition, the tallying process is very time intensive and likely to be error prone, because of the combination of complex voting rules and huge ballots. In order to address such challenges and improve the situation for both voters and electoral officials, in particular with respect to the local elections in Hesse/Germany, the EasyVote electronic voting scheme was proposed. EasyVote focuses on polling station elections and its central idea is to use an electronic voting device that does not store votes, but rather prints out a summary of voter's selections on a DIN-A4 paper ballot (a paper audit trail). The ballot consists of a human- and a machine readable (a QR-Code) component. Further, electoral officials tally the ballots semi-automatically by scanning the QR-Code of each ballot and verifying that its content matches the human-readable component. However, before EasyVote can be used in legally binding elections, various open research questions need to be addressed. The goal of this dissertation is to pave the way for the use of EasyVote in legally binding elections. To achieve this goal, this dissertation addresses five open research questions, which are introduced below. While the second and fifth question are EasyVote specific, the remaining ones are relevant to all electronic voting schemes/systems that share similar concepts with EasyVote. 1. Are voters concerned about vote secrecy related to the use of QR-Codes and, if so, how to address such concerns effectively? 2. What is an optimal ballot design that enables voters to understand the impact of their selections and to verify their voting intention easily? 3. What are optimal verification instructions that make voters most likely to verify that their ballot matches their intention? 4. What is an optimal verification setting that makes electoral officials most likely to detect potential discrepancies between the human- and machine-readable ballot components? 5. Are the vote casting and tallying processes usable and, if not, how to improve their usability? The findings indicate that voters do have secrecy concerns in association with the use of QR-Codes. However, the findings suggest that the threat appraisal approach of the protection motivation theory, is a viable approach to address and significantly allay such concerns. Furthermore, the findings reveal that the ballot design, which highlights the voter's direct selections in orange, represents an optimal design for voters to understand the impact of their selections and to verify their intention easily. In addition, the findings show that just in time verification instructions, which are pre-printed on the reverse of the ballot, have a significant effect on voters with respect to verifying their ballot and detecting discrepancies. The findings also indicate a significant increase with respect to detecting discrepancies when electoral officials read voters' direct selections out loud, while verifying that the human-readable ballot component matches the associated QR-Code. Moreover, the findings suggest that the implemented EasyVote prototype has a high perceived usability. In summary, these findings reveal that EasyVote is likely to be recommended and that a malicious or faulty behaviour of an electronic voting device, which might violate the integrity of the election result, would be detected with very high probability.

In dem Artikel wird der Einfluss des TV-Duells 2013 auf die Einschätzung einer Übereinstimmung von politischen Positionen der Kanzlerkandidaten mit deren Parteien untersucht und überprüft, welche Auswirkungen eine Bewertungsänderung für die Wahlentscheidung hat. Analysiert werden drei Hypothesen, wobei sich zeigt, dass das TV-Duell (1.) zu einem Anstieg in der Wahrnehmung Steinbrücks als Repräsentant seiner Partei führt, was (2.) wiederum für ihn positive Effekte auf die Kanzlerpräferenz mit sich brachte. Dies führte letztendlich (3.) auch zu einer gestiegenen Wahlwahrscheinlichkeit für die SPD. Damit kann der Einfluss des TV-Duells auf eine weitere Bewertungsdimension der Kandidatenorientierung und damit auf das Wahlergebnis nachgezeichnet werden. ; The article investigates the influence of the 2013 TV-debate on evaluations regarding the congruence of chancellor candidates' political positions with those of their parties. Furthermore, it analyses the impact of those evaluations on vote choice. Testing three hypotheses, we find that the TV-debate (1.) results in a considerably stronger perception of Steinbrück as a representative of his party, which in turn (2.) has had a positive effect on chancellor preference. This, in the end, (3.) has led to an increased probability to vote for the SPD. Thus, the impact of the TV-debate on a further evaluation dimension of candidate orientations and, consequently, the outcome of the election can be illustrated.

Die Untersuchung der Bewertung von Kandidaten während einer TV-Debatte mit Real-Time-Response-Messungen hat sich in der politischen Kommunikationsforschung etabliert. Das Studiendesign ermöglicht es, detailliert zu erfassen, wie individuelle Rezipienten die Kandidaten infolge einzelner Aussagen bewerten. Um die Potenziale des aufwändigen Studiendesigns voll ausschöpfen zu können und der komplexen Datenstruktur der Echtzeitmessung sowohl theoretisch als auch statistisch gerecht zu werden, ist eine Reflexion über angemessene Analyseverfahren notwendig. In dieser Arbeit werden zum einen die etablierten analytischen Zugänge kritisch diskutiert und erweitert. Zum anderen wird eine Mehrebenenmodellierung vorgeschlagen, die sich in besonderer Weise eignet, die individuellen Prozesse der Kandidatenbewertungen abzubilden. Die etablierten Verfahren und die Mehrebenenmodellierung werden anhand einer Rezeptionsstudie zum TV-Duell vor der baden-württembergischen Landtagswahl 2011 praktisch demonstriert. ; Continuous Response Measurement (CRM) as a tool to capture candidate evaluations during televised debates is well established in political communication research. Such systems allow very detailed measurements of individual responses to certain candidate statements. However, CRM studies produce very complex data structures which are not easily accessible by simple analytical procedures while at the same time preserving the individual nature of the measurement. Therefore, we first critically discuss the established analytical approaches and recommend some modifications. Second, we describe how such measurements can be adequately modeled at the individual level in a multilevel framework. All analytical approaches are demonstrated using data from a CRM study on the televised debate in the run-up to the Baden-Württemberg state election 2011.

The author offers an insight into the strategies of the SPD campaign headquarters. The goal was to make the federal election of 2002 a politically defining moment. It was important to overcome the economic & labor market crises by establishing a positive evaluation of government activities & reform perspectives, putting social-political topics on the agenda, & emphasizing one's own competencies (as well as the red-green ones). Finally, the campaign should remind the voters of the negative results of the conservative government before 1998. The focus on the person of Gerhard Schroder was crucial to winning the elections. He portrays the cultural opposite of Edmund Stoiber, who gives the impression of being a representative "of a closed, elitist, & somehow also backward-oriented circle.". Adapted from the source document.

Confronted with an utterly divided and quarrelling opposition, the coalition partners SPD and Greens managed to achieve an overwhelming victory in the Bremen state election and to win a two-thirds majority of seats in the parliament. This success represents an exception among all governing coalitions in the state elections held during the super election year 2011. The opposition parties (CDU, the Liberal Party (FDP), and the LEFT), on the contrary, lost altogether 11.6 percent of the votes. For the first time in German state elections, the Greens left behind even the CDU, while the Liberal Party failed to cross the five percent hurdle. The victory of the governing parties can be traced back not only to the disastrous condition of the opposition parties but also to the positive evaluation of their competence in all relevant policy fields and of their government performance by the voters, and this despite of rather considerable financial and social problems in the state of Bremen. The SPD's vote increase can also be credited to their top candidate lens Bohrnsen, who enjoyed high popularity and competence ratings. Considering the excellent result for the Greens, the analysis reveals that they benefited from their strong ecological profile after the nuclear catastrophe in Japan. It reflects the shift of power relations between the coalition partners in favour of the Greens that they claimed to hold three instead of two seats in the new Senate. Adapted from the source document.

Voters can use sub-national elections to punish or reward the federal government. This can be analyzed by looking at their evaluation of the federal government. Here, it is argued that it is easier for voters to assign responsibility if the same parties hold office on both the federal and state level. It is more difficult to assign responsibility if these governments are composed of different parties. Based on survey data for state elections in Berlin (1979 to 2001), it can be shown that the federal arena only influences the sub-national arena if the same parties hold both governments. However, the size of this effect is small when contrasted to other individual vote-choice determinates like party and candidate preferences at the state level. (Zeitschrift für Parlamentsfragen / FUB)

"Voters can use sub-national elections to punish or reward the federal government. This can be analyzed by looking at their evaluation of the federal government. Here, it is argued that it is easier for voters to assign responsibility if the same parties hold office on both the federal and state level. It is more difficult to assign responsibility if these governments are composed of different parties. Based on survey data for state elections in Berlin (1979 to 2001), it can be shown that the federal arena only influences the sub-national arena if the same parties hold both governments. However, the size of this effect is small when contrasted to other individual vote-choice determinates like party and candidate preferences at the state level." (author's abstract)

Numerous political initiatives and memoranda of intent have recently dealt with granting municipal suffrage to third-country nationals. However, no concrete bill has been implemented so far. In legal discourse, the legitimacy of voting rights for third-country nationals is negated generally by reference to two rulings of the German Federal Constitutional Court (FCC) in 1989. In these rulings the FCC declared the introduction of municipal suffrage for third-country nationals unconstitutional. The analysis shows that developments in international law, European law, and constitutional law, over the past twenty years have shaken both the reasoning underlying the judgments and the legal literature that until today largely follows the arguments of the court. In particular, a re-evaluation of municipal suffrage for third-country nationals is brought about by the revision of Article 28 paragraph 1 of the German Basic Law, which now grants municipal suffrage to EU citizens. Moreover, Abstracts 251 granting individuals the right to vote and stand as a candidate in elections to the European Parliament in the Member State in which one resides contributed to the re-evaluation, and, finally, through the emergence of international law-based transnational citizenship that guarantees legal status below domestic citizenship. Adapted from the source document.

Dieser Artikel behandelt die Konstruktion des religiös und kulturell Anderen im speziellen Fall der Türkei als EU-Beitrittskandidat. Es wird erklärt, dass Argumente, Aussagen, Urteile und Bewertungen aus Sicht der Europäischen Mehrheit implizit als universell und generell akzeptiert angesehen werden. Eine genauere Analyse des Gegenstands macht jedoch deutlich, dass die Europäischen Positionen Produkte ihrer eigenen sozialen und kulturellen Geschichte sind und daher nicht verallgemeinert werden können. In dieser Arbeit werden drei Paradigmen von der Position der Religion im 'modernen' Europa beschrieben. Diese sind: das Paradigma der religiösen Säkularisierung, das Paradigma rational choice und religiöser Selbstkonstruktion und das Paradigma der invisible religion. Die Analyse dieser Paradigmen zeigt, dass der europäische Blick auf die Türkei von individuellen religiösen und kulturellen Erfahrungen dominiert wird, welche den muslimischen Beitrittskandidaten in den Köpfen der Menschen verdächtig wirken lassen. Solche Überzeugungen und Gesinnungen werden fixiert, bevor der politische Diskurs beginnt und beeinflussen daher das Ergebnis der Debatte. ; This paper discusses the construction of religious and cultural others in the special case Turkey, as a candidate for joining the European Union. The thesis asserts that arguments, statements, assessments and evaluations are implicitly considered to be universal and general assumed by the European majority. However a closer study of the issue reveals that the European positions are products of their own social and cultural history, and therefore cannot be generalized. This thesis will describe three paradigms on the situation of religion in 'modern' Europe. These are: the paradigm of religious secularization, the paradigm of rational decisions and religious self conception, and the paradigm of the 'invisible religion'. A study of these will show that the European view on Turkey is dominated by individual religious and cultural experiences, which make this Muslim candidate country to appear suspicious in their minds. Such beliefs and dispositions are focused and fixed even before the start of the discourse, and therefore influence the outcome of this debate.

Aufgrund des anhaltenden Mangels an hochqualifizierten IT Fachkräften und des immensen Wettbewerbs um die besten Talente stellen sich immer mehr IT Unternehmen folgende Frage: Was kann ich als Arbeitgeber tun, damit sich spannende KandidatInnen für mein Jobangebot entscheiden? Um dieser Frage nachzugehen, wurde auf Basis einer ausführlichen Literaturrecherche ein eigenes Modell entwickelt, um die Arbeitgeberwahl im IT bzw. Softwareentwicklungsbereich zu erklären. Darauf basierend wurden im Rahmen einer Fallstudie 33 hochtalentierte Software Engineers mit Veränderungsabsicht interviewt. Diese befanden sich zum Zeitpunkt der Befragung in einem Bewerbungsprozess bei meinem aktuellen Arbeitgeber. Befragt wurden die KandidatInnen hinsichtlich der ausschlaggebenden Faktoren für ihre Entscheidung. Zusätzlich wurde eine Analyse jener Maßnahmen vorgenommen, welche der untersuchte Arbeitgeber einsetzte, um die KandidatInnen vom eigenen Unternehmen zu überzeugen. Dabei wurde zwischen zwei Arten von Maßnahmen unterschieden: 1) Signaling-Maßnahmen wie beispielsweise ein Schnuppertag, welcher Rückschlüsse auf die zukünftige Tätigkeit ermöglicht und 2) Spezialmaßnahmen abseits der gängigen Unternehmensstandards, wie beispielsweise eine einmalige finanzielle Bonuszahlung. Die Untersuchung wurde an zwei Befragungszeitpunkten angesetzt; vor und nach dem Treffen einer konkreten Entscheidung für bzw. gegen den untersuchten Arbeitgeber. Bei Betrachtung der Ergebnisse der Fallstudie wird deutlich, dass vor allem die Tätigkeit sowie das Gehalt tendenziell ausschlaggebende Faktoren für SoftwareentwicklerInnen darstellen. Auch das Betriebs- bzw. Arbeitsklima, das Ansehen in der Öffentlichkeit/im Freundeskreis, die Arbeitszeit sowie die eingesetzten Technologien spielten vor und nach der Entscheidung eine zentrale Rolle. Die weiteren Ergebnisse unterscheiden je nach Befragungszeitpunkt stark. Während Faktoren wie Weiterbildung und Relocation (Support) lediglich zu Beginn des Recruiting-Prozesses eine Rolle spielten, gewannen gewisse Faktoren wie der Recruiting-Prozesse selbst, die affektive Beurteilung ("Bauchgefühl") sowie die Kompetenz des Unternehmens zum Befragungszeitpunkt nach getroffener Entscheidung an Bedeutung. Neben dem Recruiting-Prozess wurden im Rahmen der Fallstudie nur wenige weitere Signaling-Maßnahmen eingesetzt. Hingegen war die Anzahl individueller Spezialmaßnahmen, um KandidatInnen bei Spezialwünschen entgegenzukommen, sehr hoch. Dies deutet darauf hin, dass das untersuchte Unternehmen an der Verbesserung der unternehmensweiten Standards arbeiten sollte. Auf Basis der Ergebnisse der Fallstudie wurden Handlungsempfehlungen für von IT Fachkräftemangel betroffene Unternehmen abgeleitet. Vor allem am Recruiting-Prozess sowie im Bereich Arbeitszeit können positive Veränderungen an zentralen Faktoren ohne hohe Kostenbelastung vorgenommen werden. Hinsichtlich kostspieliger Maßnahmen muss jedes Unternehmen für sich entscheiden, in welchen Bereichen der größte Hebel wahrgenommen wird. Auch die Kommunikation bzw. das Signaling der Faktoren darf nicht zu kurz kommen. Nur wenn die Wahrnehmung der jeweils individuell wichtigsten Faktoren stimmt, ist es wahrscheinlich, dass das Angebot des Unternehmens letztendlich angenommen wird. ; Due to the scarcity of high-qualified IT specialists, more and more IT companies start asking themselves what they can do to convince highly-talented professionals to start working at their companies. To answer this question, I used well-known employment literature as well as my very own case study to come up with an elaborate model to explain the choice for an employer. This model aims to identify the most relevant parameters for making the decision and shall also show how IT companies can effectivily work on those parameters to be at an advantage. Regarding the case study, I interviewed 33 highly talented Software Engineers willing to change jobs. I interviewed them twice during the recruiting process; before and after the decision making. I asked the candidates for their individual most important key parameters regarding the decision for their future job/employer and also analyzed which additional actions my employer took to convince the candidates of the company. I distinguished between two kinds of actions; 1) signaling measures like walking candidates around the office so they can catch a glimpse of the office culture and 2) special treatments besides the company-wide standards like offering a financial bonus. Looking at the results, I found that especially the task/position as well as the entry salary trend to be very important key parameters for highly-talented Software Engineers. Also the working atmosphere, the companys reputation, working hours and used technologies were mentioned several times. It showed that the results differ according to the point in the recruiting process the questions were asked. Whereas parameters like training and relocation (support) were only mentioned at the beginning of the process, other parameters like the recruiting process itself, affective evaluation ('gut feeling') and the companys (and its employee's) expertise became more important during the decision making. This could be explained due to the fact that the recruiting process helps the candidates to catch a glimpse of company atributes which could not be verified before. Since most of the candidates liked the process, the companys expertise etc., I assume that the positive experiences during the recruiting process shaped their opinion and made most of them accept the offer in the end (25 of 33 candidates). In addition to the recruiting process, the company also used a small number of signaling measures to help the candidates getting a better picture of certain attributes which are hard to varify before starting to work at the company. This number could be improved/raised in my opinion, whereas the number of special treatments should decrease (not all of the latter were focused on the mentioned key parameters and also not only used on Triple A players ). ^Based on the case studys results, I came up with suggestions for IT companies facing similar challenges regarding the hiring of highly-qualified software engineers. At first, it is essential to focus on the most important key parameters the candidates mention(ed). Since too many special treatments for new hires are exhausting and unfair regarding the existing staff, I would suggest to work on the affected companywide standards instead. Especially the recruiting process and working hours can easily be adjusted without huge costs. Regarding more expensive actions, every company has to decide for itself where it sees room for improvement. Its also essential to communicate the benefits to the candidates. Only if they have all the necessary information needed regarding their most important key parameters, the companys offer is likely to be accepted. ; eingereicht von Kerstin Eidinger ; Universität Linz, Masterarbeit, 2019 ; (VLID)3685808

"Confronted with an utterly divided and quarrelling opposition, the coalition partners SPD and Greens managed to achieve an overwhelming victory in the Bremen state election and to win a two-thirds majority of seats in the parliament. This success represents an exception among all governing coalitions in the state elections held during the super election year 2011. The Opposition parties (CDU, the Liberal Party (FDP), and the LEFT), on the contrary, lost altogether 11.6 percent of the votes. For the first time in German state elections, the Greens left behind even the CDU, while the Liberal Party failed to cross the five per-cent hurdle. The victory of the governing parties can be traced back not only to the disastrous condition of the opposition parties but also to the positive evaluation of their competence in all relevant policy fields and of their government performance by the voters, and this despite of rather considerable financial and social problems in the state of Bremen. The SPD's vote increase can also be credited to their top candidate Jens Böhrnsen, who enjoyed high popularity and competence ratings. Considering the excellent result for the Greens, the analysis reveals that they benefited from their strong ecological profile alter the nuclear catastrophe in Japan. It reflects the shift of power relations between the coalition partners in favor of the Greens that they claimed to hold three instead of two seats in the new Senate." (author's abstract)

Die vorliegende Arbeit beschäftigt sich mit der Untersuchung des institutionellen Wandels in Polen, Tschechien und Ungarn während ihres Beitrittsprozesses zur Europäischen Union. Dabei liegt das Hauptaugenmerk auf den dabei entstandenen Wechselwirkungen zwischen Parteipolitik und den Beitrittsbemühungen. Die Entwicklungen in Mittelosteuropa nach dem Ende der Blockkonfrontation zwang die neuen Demokratien in der Region in einen Zustand des demokratischen und ökonomischen Wettbewerbs um den Zutritt zu westeuropäischen Strukturen, die Wohlstand und Sicherheit versprachen. Die Mitgliedschaft in der EU wurde von ihnen als oberstes Ziel, wenn nicht sogar als Belohnung, ihrer gesellschaftlichen Transformation verstanden. Die Konsolidierung der Demokratie war - im Gegensatz zur vorherigen Demokratisierung - in diesem Zusammenhang keine explizite Anforderung, sondern eine positive Prognose, die spätestens mit der EU-Mitgliedschaft der Realität entsprechen sollte. Das Kernstück dieser Arbeit ist die komparative Dreiländerstudie, in der die innenpolitischen Ereignisse, die Motive der Akteure, die Funktionalität der jeweiligen politischen Systeme und deren Entwicklung nach der Errichtung der Demokratie verglichen werden. Außerdem werden die Strukturen untersucht, die von den Kandidatenländern erschaffen worden sind, um den Beitritt zu organisieren. Die abschließende Bewertung erfolgt hinsichtlich der Gründe, die für etwaige institutionelle Veränderungen verantwortlich waren sind und arbeitet die europapolitischen Determinanten für das Akteursverhalten heraus. Die Verknüpfung von externer Einflußnahme mit institutionellem Wandel im Inneren führt zu folgenden politikwissenschaftlich relevanten Fragen: In wie weit hat der Beitrittsprozeß einen Einfluß auf die Konsolidierung der Demokratie in den Kandidatenländern gehabt? Hatte der Beitrittsprozeß kurz- oder langfristige Veränderungen in den politischen Systemen dieser Länder zur Folge? Haben die nationalen Akteure versucht, den Beitrittsprozeß für ihre eigenen politischen Ziele zu instrumentalisieren? Die Beantwortung dieser Fragen wird helfen, die innenpolitischen Konsequenzen zukünftiger Erweiterungsrunden besser einzuschätzen, einschließlich den dabei zu erwartenden politischen Wechselwirkungen auf der nationalen Ebene der neuen Mitgliedsstaaten. ; The present work deals with the research of institutional change in Poland, the Czech Republic and Hungary during the accession process to the European Union. The main emphasis rests on the interaction between domestic party politics and accession efforts that took place during this period. The developments in Central Eastern Europe after the end of the East-West conflict forced the new democracies of the region into a state of economic competition for entry to West European structures that promised wealth and security. The membership in the EU was perceived as the main foreign policy objective if not as the reward for their societal transformation. The consolidation of democracy - in contrast to the previous democratization that took place - wasn''t a specific requirement in this context. Instead it was a positive prediction which was believed to come true with the EU-membership at the latest. The central element of this work is a comparative three country study, analyzing the domestic political events, the motives of the actors, the functionality of the given political systems and their development after the initial establishment of institutional democracy. Furthermore it includes an examination of the structures that have been created by the candidate countries for organizing their accession to the EU. The final evaluation is done in regard to the reasons responsible for domestic institutional changes and means an attempt to work out the Europe centered determinants of the domestic actors'' behaviours. The linking of external influence to domestic institutional change leads to the following questions relevant to political science: To what extent the accession process had an impact on the consolidation of democracy in the candidate countries? Has the accession process caused any short or long term changes in the political systems of these countries? Have the domestic actors tried to utilize the accession process for their own political interests? The answers to these questions will help evaluating the domestic consequences of future enlargement rounds, including the correlations on the national level of the new member states.

Alternative methods in ecotoxicology play an increasingly important role in chemical and risk assessment. Already in 1986, the Directive 86/609/EEC stated that an alternative method, once it is "practicably and reasonably available", should replace the corresponding animal method. In 2007, REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) came into force to systematically evaluate the risk to human health and the environment of approx. 30,000 chemical substances produced, used or imported in quantities of 1 - 100 t/a. Within the framework of REACH, animal testing should be reduced or even replaced by alternative methods. The 96 h acute fish test, however, is still a mandatory component in the base set of data required for chemical risk assessment. With mortality as the exclusive endpoint, it is not compatible with most current animal welfare legislations in Europe. Furthermore, there is increasing concern that some form of pain perception, similar to what is present in mammals, may be present in bony fish, and adult fish exposed to acute toxic concentrations of chemicals may at least be suspected to suffer severe distress and pain. A promising candidate to replace the acute fish test in chemical assessment is the fish embryo toxicity (FET) test. In Germany, the FET has already replaced the acute fish test in whole effluent testing since 2005. A major advantage of the FET concerning animal welfare is the fact that embryos may have not yet developed the same complex mental processes and may have not pain perception identical to adult fish. Since the correlation between the alternative and the test to be replaced is one of the most important facts to accept a test as alternative, a detailed literature research and a thorough re-evaluation of FET and acute fish test data has been conducted. The analyses resulted in an overall R2 of 0.90 for the comparison of FET data and acute fish test data. Restricting the data to zebrafish (Danio rerio) FET data and all fish data, the correlation resulted in an R2 of 0.87. In general, all correlations with different restrictions of the complete dataset (e.g. only zebrafish FET and zebrafish acute fish test data, only 48 h FET and 96 h fish toxicity data, etc.) showed no R2 lower than 0.81. For comparison between different biotests, these are almost perfect correlations, and compared to correlations of 96 h acute fish data among different fish species, they are in the same range or even better. However, outliers are inevitable. In order to investigate if the static procedure of the FET may be the reason for outliers, a flow-through protocol was developed. The applicability of the flow-through system in chemical assessment was checked by testing four different "outlier chemicals" (hydroquinone, 4-chlorophenol, pyraclostrobin and α-endosulfan), which were selected according to increasing log Pow. Independent of chemical nature and lipophilicity, the flow-through and the static FET gave almost identical results for all substances. Thus, at least for these chemicals, the differences between the results from the FET and the acute fish toxicity test could not be traced back to reduced bioavailability due to adsorption to the polystyrene plates. Further investigations are necessary to identify reasons for the poor correlation between FET and acute fish test results for specific chemicals. However, the static protocol seems to be a sufficient testing procedure and should definitely be used in further chemical assessment.

Der Kernrezeptor PXR spielt eine bedeutende Rolle im Fremdstoffmetabolismus als auch im Stoffwechsel endogener Substrate. Er reguliert die Expression zahlreicher Proteine des Fremdstoffwechsels. Deshalb hat die Aktivierung oder Hemmung des PXR einen großen Einfluss auf den Stoffwechselstatus dieser Proteine. Zum derzeitigen Stand der Forschung nimmt der PXR eine Schlüsselfunktion bei der Regulation der CYP3A-Enzyme ein. Es besteht deshalb Interesse Substanzen, die in Verdacht stehen PXR abhängig CYP3A zu induzieren, zu untersuchen. In dieser Arbeit wurden bromierte Flammschutzmittel und der Arzneimittelkandidat EMD untersucht. Aus den Vorversuchen wurde ersichtlich, dass die Rattenhepatomzelllinie H4IIE und die humane Hepatomzelllinie HepG2 geeignete in vitro Systeme zur Untersuchung der PXR-abhängigen CYP3A-Aktivierung darstellen. Untersuchungen zum Genexpressionsverhalten zahlreicher Gene des Fremdstoffmetabolismus mittels TLDA-Karten zeigten, dass die beiden Zelllinien viele dieser Gene exprimieren, die nach Inkubation mit den Prototypinduktoren Rifampicin und Dexamethason spezies-spezifisch reguliert wurden. Die beiden Zelllinien wurden schließlich mit einem Reportergenvektor, der die PXR responsiven Elemente des CYP3A4-Gens enthält, stabil transfiziert. An den stabil transfizierten HepG2-XREM3- und H4IIE-XREM3-Zellen wurden bekannte CYP-Induktoren sowie der Arzneimittelkandidat EMD und die Flammschutzmittel HBCD and der pentaBDE Mix getestet. Die Flammschutzmittel HBCD und der pentaBDE-Mix, werden in Textilwaren, Kunststoffen, Möbeln, Teppichen, Elektrogeräten und Baumaterialen eingesetzt. Falls sie tatsächlich den PXR spezies-spezifisch aktivieren sollten, könnten sie eine Gefahr für Mensch und Umwelt darstellen. Deshalb wurde in dieser Arbeit die CYP3A-mRNA-Expression, die Protein- sowie die Reportergenaktivität überprüft. Als gemeinsamer Aktivator des hPXR und rPXR stellte sich Clotrimazol, aber auch das Flammschutzmittel HBCD heraus, während pentaBDE ein besserer Ligand des hPXR ist. Omeprazol und Phenobarbital induzierten die rPXR-vermittelte CYP3A-Induktion in H4IIE-XREM3-Zellen nicht; in den humanen HepG2-XREM3-Zellen konnte jedoch eine moderate Reportergenaktivität gemessen werden. Weiteres Interesse besteht an dem Arzneimittelkandidaten EMD zur Behandlung des metabolischen Syndroms und Typ II-Diabetes. In vivo (Affen, Ratten) und in vitro (Hepatozyten) wurden bereits spezies-spezifische Effekte auf die CYP3A-Induktion durch EMD beobachtet. Deshalb wurde in dieser Arbeit der über aktivierten PXR vermittelte Mechanismus an Zelllinien überprüft. Dabei stellte sich heraus, dass EMD ein hPXR-Aktivator und CYP3A-Induktor in HepG2-Zellen, jedoch kein Aktivator von rPXR in H4IIE-Zellen ist. Um schwerwiegende Nebenwirkungen und unvorhersehbare Arzneimittelwechselwirkungen durch die Aufnahme von Fremdstoffen zu verhindern, ist es bei der Neuentwicklung von Wirkstoffen aller Art notwendig, die Stoffe auf eine mögliche Induktion der Fremdstoff-metabolisierenden Enzyme zu untersuchen. Deshalb war das Ziel dieser Arbeit die Etablierung von zell-basierten in vitro Assays zur Ermittlung der spezies-spezifischen PXR-abhängigen Induktion von CYP3A durch Chemikalien und Arzneimittelkandidaten, um mögliche Arzneimittel- und Fremdstoffwechselwirkungen und damit verbundene Sicherheitsrisiken vorhersagen zu können. Das etablierte PXR- Screeningsystem repräsentiert zwei in vitro Modelle, die erlauben spezies-spezifische Wirkungen auf die CYP3A-Induktion von Chemikalien, Umweltkontaminanten, Lebensmittelinhaltsstoffe und Arzneimittel schnell, einfach und kostengünstig abschätzen zu können. Eine frühe Erkennung der PXR-Aktivierung und CYP-Induktion von Arzneimitteln in der Entwicklung kann einen Weiterentwicklungsstopp dieser zur Folge haben. Dies hilft zusätzliche Tierversuche und Kosten einzusparen. Dem 3R-Prinzip (Reduce, Refine, Replace) vom Reduzieren der Anzahl der Tierversuche, der Verbesserung der existierenden Experimente und dem Ersetzen von Tierversuchen durch alternative Methoden (Russel & Burch, 1959) wird durch die stabil transfizierten Zelllinien in zweierlei Hinsicht Rechnung getragen: unnötige Tierversuche können vermieden reduction und die Aussagekraft von durchgeführten Tierstudien (z.B. vom Gesetzgeber geforderte Studien zur Arzneimittelentwicklung) verbessert werden (dies trägt auch zu einem refinement bei). Damit stellen die HepG2-XREM3- und H4IIE-XREM3-Zellen eine wichtige innovative Verbesserung bei der Entwicklung von Arzneistoffen sowie bei der regulatorischen Testung von Chemikalien dar. ; Pre-tests showed that the rat and the human hepatoma cell lines H4IIE and HepG2 represent suitable in vitro systems for the investigation of the PXR dependent CYP3A induction. Examinations of characteristics in gene expression of numerous genes of the drug metabolism using TLDA cards indicated that both cell lines express many of these genes which were regulated species specific after incubation with the prototypical PXR agonists rifampicine and dexamethasone. Both cell lines were then stably transfected with a reporter gene containing the PXR responsive elements that mediate the regulation of PXR target genes such as CYP3A. With the stably transfected human HepG2-XREM3- and rat H4IIE-XREM3-cells well-known CYP-inducers as well as the drug candidate EMD and the BFRs HBCD and the pentaBDE mix were screened. The BFRs HBCD and pentaBDE mix are used in textiles, plastics, furniture, carpets, electrical equipments and construction materials. If they would actually activate PXR species specific they may pose unpredictive hazards for humans and environment. Hence, CYP3A mRNA expression, protein, reporter gene activity were screened in a species specific manner. In the human HepG2-XREM3- and rat H4IIE-XREM3-cells, clotrimazole and HBCD were found as common activators of the human and rat PXR whereas pentaBDE is preferred by the hPXR. Omeprazole and Phenobarbital did not induce the rPXR dependent CYP3A induction in H4IIE-XREM3-cells, but a moderate reporter gene activity could be measured in HepG2-XREM3-cells. Another interest exists in the drug candidate EMD for the treatment of "metabolic syndrome" and type 2 diabetes. In vivo (monkeys, rats) and in vitro (hepatocytes) species specific effects on the CYP3A induction by EMD were already noticed. Therefore, the mode of action of these effects was analyzed for PXR activation in these cell lines. EMD was an hPXR activator and CYP3A inducer in HepG2 cells but no activator of rPXR in H4IIE cells proving its species specific activation observed in vivo. In order to prevent serious adverse effects or unpredicted drug-drug interactions (DDI) by the intake of drugs it is necessary to investigate the possible induction of drug metabolizing enzymes of drugs in the development. Therefore, the aim of this work was to establish cell-based in vitro assays for the evaluation of the species specific PXR dependent induction of CYP3A of chemicals and drug development candidates to predict potential DDI and related safety hazards. The established PXR screening system represents in vitro systems that permit to evaluate simultaneously, fast, simple and cost-effective the species specific effects on the CYP3A induction in humans and rats of chemicals, environmental contaminants, food ingredients and drugs. An early identification of PXR activation and CYP induction of drugs in development can help in the decision to discontinue or advance their further development. This will help to reduce and avoid useless animal experiments. The 3R principles of reducing the number of animal tests, the refinement of existing experiments and the replacement of animal experiments by new and alternative methods (Russel & Burch, 1959) are taken into account by the stably transfected cell lines twofold: unnecessary animal experiments can be avoided ("reduction") and the data interpretation of animal tests (e.g. from the legislator claimed studies for drug development) can be improved (this contributes to a "refinement"). For this reason HepG2-XREM3- and H4IIE-XREM3-cells represent an important innovative improvement for the development of drugs as well as for the regulatory testing of chemicals.