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El lunfardo : Kontaktvarietät der Migrationskultur am Rio de la Plata und in der Welt des Tango
(2014)
Zwischen Liberalismus und Christentum : die sozialethischen Aspekte der sozialen Marktwirtschaft
(2014)
Sex-specific differences in the regulation of body weight dynamics and adipose tissue metabolism
(2014)
Regeln virtueller Welten
(2014)
Enterprise-specific in-memory data managment : HYRISEc - an in-memory column store engine for OLXP
(2014)
Der Häftlingsfreikauf aus der DDR 1962/63 - 1989 : zwischen Menschenhandel und humanitären Aktionen
(2014)
Diese Arbeit befasst sich mit den sogenannten relativähnlichen Sätzen im Frühneuhochdeutschen und leistet somit einen Beitrag zur Subordinationsforschung des älteren Deutsch. Relativähnliche Sätze sind formal durch ein satzinitiales anaphorisches d-Element und die Endstellung des finiten Verbs gekennzeichnet. Semantisch gesehen beziehen sie sich auf den vorangehenden Satz als Ganzes, indem sie ihn in bestimmter Weise weiterführen oder kommentieren. In der bisherigen Forschung werden diese Sätze satztypologisch als Hauptsätze mit Verbendstellung analysiert (vgl. dazu Maurer 1926, Behaghel 1932 und Lötscher 2000). Nach der ausführlichen Diskussion der formalen Abhängigkeitsmarker im älteren Deutsch sowie anhand einer umfangreichen korpusbasierten Untersuchung wird in dieser Arbeit gezeigt, dass relativähnliche Sätze im Frühneuhochdeutschen auch als abhängige Sätze - analog zu den weiterführenden Relativsätzen im Gegenwartsdeutschen - analysiert werden können. Die weiterführenden Relativsätze im Gegenwartsdeutschen enthalten satzinitial auch ein anaphorisches Element, das sich auf das Gesagte in dem vorangehenden Satz bezieht. Verbendstellung weisen sie ebenfalls auf (mehr zur Grammatik der weiterführenden Relativsätze vgl. insb. Brandt 1990 und Holler 2005). Über die Untersuchung relativähnlicher Sätze hinaus befasst sich diese Arbeit ausführlich mit formalen Abhängigkeitsmarkern des älteren Deutsch, wie Verbendstellung, Einleiter und afinite Konstruktion.
עבירה לשמה
(2014)
A Transgression for the Sake of God -‘Averah li-shmah: A Tale of a Radical Idea in Talmudic Literature
All cultures, religions, and ethical or legal systems struggle with the role intention plays in evaluating actions. The Talmud compellingly elaborates on the notion of intention through the radical concept that “A sin committed for the sake of God [averah li-shmah] is greater than a commandment fulfilled not for the sake of God [mi-mizvah she-lo li-shmah].” The Babylonian Talmud attributes this concept—which challenges one of rabbinic Judaism’s most fundamental dogmas, the obligation to fulfill the commandments and avoid sin—to R. Nahman b. Isaac (RNBI), a renowned 4th century Amora. Considering the normative character of the rabbinic culture in which Halakhah (Jewish religious law) plays such a central role, this concept, seems almost like a foreign body in the Talmudic corpus.
The study focuses on the linguistic stratum of RNBI’s statement. By tracking the development of the meanings and uses of the word ‘li-shmah’ the research locates RNBI’s statement as part of the broader Talmudic discourse evaluating two levels of performing religious actions ‘li-shmah/she-lo li-shmah’. Since we wish to explain the word ‘li-shmah’ consistently both times it appears in the statement, the best translation would be ‘for the sake of God’. This translation is based on the linguistic connection between the word ‘li-shmah’ and the term ‘le-shem shamayim’ (for the sake of God) that appears in several rabbinic sources. This linguistic connection is also the key to identifying the possible root of RNBI’s concept. RNBI bolsters his idea by quoting a verse about Jael, thus implying that Jael sinned for the sake of God. The research describes at least five statements in Sages’ Literature that attribute sins for the sake of God to other biblical figures, all the while using the term ‘le-shem shamim’. Therefore we may presume that RNBI’s concept has evolved from the exegetical notion of attributing sin for the sake of God to biblical figures.
To understand the way RNBI’s statement was accepted in Talmudic culture, we must explore the textual witnesses to the literary frame of RNBI’s statement: the Talmudic sugya (Nazir 23a; Horayot 10b). We possess five versions of the sugya’s dialectical structure. Comparison of these versions, allows us to reconstruct the earlier dialectical structure, from which the familiar versions developed. The radical potential of RNBI’s statement led to cultural activity, in the transmission of the sugya, in an effort to mitigate it. This activity is reflected in late additions to the sugya identified by our research—which should be viewed as a process of self-censorship for ideological reasons.
This research explores a fundamental issue in rabbinic world: the immanent contradiction between law and intention. The research depicts in detail the movement of a radical idea from the margins culture to mainstream - in this case into the Babylonian Talmud. Therefore, the findings of this research provide substantial insight into our understanding of the interpretive process and of conceptual adaptation in rabbinic culture.
Cette recherche a pour objet l'articulation entre les dimensions anthropologiques et sociologiques de l'anthropologie philosophique de Helmuth Plessner (1892-1985). Elles procèdent selon trois axes. Je m'efforce (1) d'offrir une synthèse de l'anthropologie philosophique plessnerienne afin (2) de reconstituer les conditions de possibilité du social au stade humain de l'organique. Le troisième axe (3) correspond, enfin, à l'analyse des limites structurelles du social à partir de ses deux dimensions constitutives : l'individuel (limites ontogénétiques, comportementales et inter-personnelles) et le collectif (limites culturelles, intra- et inter-culturelles).
Die Häufung von Diabetes, Herz-Kreislauf-Erkrankungen und einigen Krebsarten, deren Entstehung auf Übergewicht und Bewegungsmangel zurückzuführen sind, ist ein aktuelles Problem unserer Gesellschaft. Insbesondere mit fortschreitendem Alter nehmen die damit einhergehenden Komplikationen zu. Umso bedeutender ist das Verständnis der pathologischen Mechanismen in Folge von Adipositas, Bewegungsmangel, des Alterungsprozesses und den Einfluss-nehmenden Faktoren.
Ziel dieser Arbeit war die Entstehung metabolischer Erkrankungen beim Menschen zu untersuchen. Die Auswertung von Verlaufsdaten anthropometrischer und metabolischer Parameter der 584 Teilnehmern der prospektiven ‚Metabolisches Syndrom Berlin Potsdam Follow-up Studie‘ wies für die gesamte Kohorte einen Anstieg an Übergewicht, ebenso eine Verschlechterung des Blutdrucks und des Glukosestoffwechsels auf. Wir untersuchten, ob das Hormon FGF21 Einfluss an dem Auftreten eines Diabetes mellitus Typ 2 (T2DM) oder des Metabolischen Syndroms (MetS) hat. Wir konnten zeigen, dass Personen, die später ein MetS entwickeln, bereits zu Studienbeginn einen erhöhten FGF21-Spiegel, einen höheren BMI, WHR, Hb1Ac und diastolischen Blutdruck aufwiesen. Neben FGF21 wurde auch Vaspin in diesem Zusammenhang untersucht. Es zeigte sich, dass Personen, die später einen T2DM entwickeln, neben einer Erhöhung klinischer Parameter tendenziell erhöhte Spiegel des Hormons aufwiesen. Mit FGF21 und Vaspin wurden hier zwei neue Faktoren für die Vorhersage des Metabolischen Syndroms bzw. Diabetes mellitus Typ 2 identifiziert.
Der langfristige Effekt einer Gewichtsreduktion wurde in einer Subkohorte von 60 Personen untersucht. Der überwiegende Teil der Probanden mit Gewichtsabnahme-Intervention nahm in der ersten sechsmonatigen Phase erfolgreich ab. Jedoch zeigte sich ein deutlicher Trend zur Wiederzunahme des verlorenen Gewichts über den Beobachtungszeitraum von fünf Jahren. Von besonderem Interesse war die Abschätzung des kardiovaskulären Risikos über den Framingham Score. Es wurde deutlich, dass für Personen mit konstanter Gewichtsabnahme ein deutlich geringeres kardiovaskuläres Risiko bestand. Hingegen zeigten Personen mit konstanter Wiederzunahme oder starken Gewichtsschwankungen ein hohes kardiovaskuläres Risiko. Unsere Daten legten nahe, dass eine erfolgreiche dauerhafte Gewichtsreduktion statistisch mit einem erniedrigten kardiovaskulären Risiko assoziiert ist, während Probanden mit starken Gewichtsschwankungen oder einer Gewichtszunahme ein gesteigertes Risiko haben könnten.
Um die Interaktion der molekularen Vorgänge hinsichtlich der Gewichtsreduktion und Lebensspanne untersuchen zu können, nutzen wir den Modellorganismus C.elegans. Eine kontinuierliche Restriktion wirkte sich verlängernd, eine Überversorgung verkürzend auf die Lebensspanne des Rundwurms aus. Der Einfluss eines zeitlich eingeschränkten, intermittierenden Nahrungsregimes, analog zum Weight-Cycling im Menschen, auf die Lebensspanne war von großem Interesse. Dieser regelmäßige Wechsel zwischen ad libitum Fütterung und Restriktion hatte in Abhängigkeit von der Häufigkeit der Restriktion einen unterschiedlich starken lebensverlängernden Effekt. Phänomene, wie Gewichtswiederzunahmen, sind in C.elegans nicht zu beobachten und beruhen vermutlich auf einem Mechanismus ist, der evolutionär jünger und in C.elegans noch nicht angelegt ist.
Um neue Stoffwechselwege zu identifizieren, die die Lebensspanne beeinflussen, wurden Metabolitenprofile genetischer als auch diätetischer Langlebigkeitsmodelle analysiert. Diese Analysen wiesen den Tryptophan-Stoffwechsel als einen neuen, bisher noch nicht im Fokus stehenden Stoffwechselweg aus, der mit Langlebigkeit in Verbindung steht.
The aim of the present thesis is to answer the question to what degree the processes involved in sentence comprehension are sensitive to task demands. A central phenomenon in this regard is the so-called ambiguity advantage, which is the finding that ambiguous sentences can be easier to process than unambiguous sentences. This finding may appear counterintuitive, because more meanings should be associated with a higher computational effort. Currently, two theories exist that can explain this finding.
The Unrestricted Race Model (URM) by van Gompel et al. (2001) assumes that several sentence interpretations are computed in parallel, whenever possible, and that the first interpretation to be computed is assigned to the sentence. Because the duration of each structure-building process varies from trial to trial, the parallelism in structure-building predicts that ambiguous sentences should be processed faster. This is because when two structures are permissible, the chances that some interpretation will be computed quickly are higher than when only one specific structure is permissible. Importantly, the URM is not sensitive to task demands such as the type of comprehension questions being asked.
A radically different proposal is the strategic underspecification model by Swets et al. (2008). It assumes that readers do not attempt to resolve ambiguities unless it is absolutely necessary. In other words, they underspecify. According the strategic underspecification hypothesis, all attested replications of the ambiguity advantage are due to the fact that in those experiments, readers were not required to fully understand the sentence.
In this thesis, these two models of the parser’s actions at choice-points in the sentence are presented and evaluated. First, it is argued that the Swets et al.’s (2008) evidence against the URM and in favor of underspecification is inconclusive. Next, the precise predictions of the URM as well as the underspecification model are refined. Subsequently, a self-paced reading experiment involving the attachment of pre-nominal relative clauses in Turkish is presented, which provides evidence against strategical underspecification. A further experiment is presented which investigated relative clause attachment in German using the speed-accuracy tradeoff (SAT) paradigm. The experiment provides evidence against strategic underspecification and in favor of the URM. Furthermore the results of the experiment are used to argue that human sentence comprehension is fallible, and that theories of parsing should be able to account for that fact. Finally, a third experiment is presented, which provides evidence for the sensitivity to task demands in the treatment of ambiguities. Because this finding is incompatible with the URM, and because the strategic underspecification model has been ruled out, a new model of ambiguity resolution is proposed: the stochastic multiple-channel model of ambiguity resolution (SMCM). It is further shown that the quantitative predictions of the SMCM are in agreement with experimental data.
In conclusion, it is argued that the human sentence comprehension system is parallel and fallible, and that it is sensitive to task-demands.
Obwohl in den unionalen Verträgen bis heute keine Vorschrift bezüglich einer Staatshaftung der Mitgliedstaaten für Entscheidungen ihrer Gerichte existiert, hat der Gerichtshof der Europäischen Union (EuGH) in einer Reihe von Entscheidungen eine solche Haftung entwickelt und präzisiert. Die vorliegende Arbeit analysiert eingehend diese Rechtsprechung mitsamt den sich daraus ergebenden facettenreichen Rechtsfragen. Im ersten Kapitel widmet sich die Arbeit der historischen Entwicklung der unionsrechtlichen Staatshaftung im Allgemeinen, ausgehend von dem bekannten Francovich-Urteil aus dem Jahr 1991. Sodann werden im zweiten Kapitel die zur Haftung für judikatives Unrecht grundlegenden Entscheidungen in den Rechtssachen Köbler und Traghetti vorgestellt. In dem sich anschließenden dritten Kapitel wird der Rechtscharakter der unionsrechtlichen Staatshaftung – einschließlich der Frage einer Subsidiarität des unionsrechtlichen Anspruchs gegenüber bestehenden nationalen Staatshaftungsansprüchen – untersucht. Das vierte Kapitel widmet sich der Frage, ob eine unionsrechtliche Staatshaftung für judikatives Unrecht prinzipiell anzuerkennen ist, wobei die wesentlichen für und gegen eine solche Haftung sprechenden Argumente ausführlich behandelt und bewertet werden. Im fünften Kapitel werden die im Zusammenhang mit den unionsrechtlichen Haftungsvoraussetzungen stehenden Probleme der Haftung für letztinstanzliche Gerichtsentscheidungen detailliert erörtert. Zugleich wird der Frage nachgegangen, ob eine Haftung für fehlerhafte unterinstanzliche Gerichtsentscheidungen zu befürworten ist. Das sechste Kapitel befasst sich mit der Ausgestaltung der unionsrechtlichen Staatshaftung für letztinstanzliche Gerichtsentscheidungen durch die Mitgliedstaaten, wobei u.a. zur Anwendbarkeit der deutschen Haftungsprivilegien bei judikativem Unrecht auf den unionsrechtlichen Staatshaftungsanspruch Stellung genommen wird. Im letzten Kapitel wird der Frage nachgegangen, ob der EuGH überhaupt über eine Kompetenz zur Schaffung der Staatshaftung für letztinstanzliche Gerichtsentscheidungen verfügte. Abschließend werden die wichtigsten Ergebnisse der Arbeit präsentiert und ein Ausblick auf weitere mögliche Auswirkungen und Entwicklungen der unionsrechtlichen Staatshaftung für judikatives Unrecht gegeben.
Atmospheric interactions with land surface in the arctic based on regional climate model solutions
(2014)
Scientific inquiry requires that we formulate not only what we know, but also what we do not know and by how much. In climate data analysis, this involves an accurate specification of measured quantities and a consequent analysis that consciously propagates the measurement errors at each step. The dissertation presents a thorough analytical method to quantify errors of measurement inherent in paleoclimate data. An additional focus are the uncertainties in assessing the coupling between different factors that influence the global mean temperature (GMT).
Paleoclimate studies critically rely on `proxy variables' that record climatic signals in natural archives. However, such proxy records inherently involve uncertainties in determining the age of the signal. We present a generic Bayesian approach to analytically determine the proxy record along with its associated uncertainty, resulting in a time-ordered sequence of correlated probability distributions rather than a precise time series. We further develop a recurrence based method to detect dynamical events from the proxy probability distributions. The methods are validated with synthetic examples and
demonstrated with real-world proxy records. The proxy estimation step reveals the interrelations between proxy variability and uncertainty. The recurrence analysis of the East Asian Summer Monsoon during the last 9000 years confirms the well-known `dry' events at 8200 and 4400 BP, plus an additional significantly dry event at 6900 BP.
We also analyze the network of dependencies surrounding GMT. We find an intricate, directed network with multiple links between the different factors at multiple time delays. We further uncover a significant feedback from the GMT to the El Niño Southern Oscillation at quasi-biennial timescales. The analysis highlights the need of a more nuanced formulation of influences between different climatic factors, as well as the limitations in trying to estimate such dependencies.
Tierische und menschliche Fäkalien aus Landwirtschaft und Haushalten enthalten zahlreiche obligat und opportunistisch pathogene Mikroorganismen, deren Konzentration u. a. je nach Gesundheitszustand der betrachteten Gruppe schwankt. Neben den Krankheitserregern enthalten Fäkalien aber auch essentielle Pflanzennährstoffe (276) und dienen seit Jahrtausenden (63) als Dünger für Feldfrüchte. Mit der unbedarften Verwendung von pathogenbelastetem Fäkaldünger steigt jedoch auch das Risiko einer Infektion von Mensch und Tier. Diese Gefahr erhöht sich mit der globalen Vernetzung der Landwirtschaft, z. B. durch den Import von kontaminierten Futter- bzw. Lebensmitteln (29).
Die vorliegende Arbeit stellt die milchsaure Fermentation von Rindergülle und Klärschlamm als alternative Hygienisierungsmethode gegenüber der Pasteurisation in Biogasanlagen bzw. gebräuchlichen Kompostierung vor.
Dabei wird ein Abfall der Gram-negativen Bakterienflora sowie der Enterokokken, Schimmel- und Hefepilze unter die Nachweisgrenze von 3 log10KbE/g beobachtet, gleichzeitig steigt die Konzentration der Lactobacillaceae um das Tausendfache. Darüber hinaus wird gezeigt, dass pathogene Bakterien wie Staphylococcus aureus, Salmonella spp., Listeria monocytogenes, EHEC O:157 und vegetative Clostridum perfringens-Zellen innerhalb von 3 Tagen inaktiviert werden. Die Inaktivierung von ECBO-Viren und Spulwurmeiern erfolgt innerhalb von 7 bzw. 56 Tagen. Zur Aufklärung der Ursache der beobachteten Hygienisierung wurde das fermentierte Material auf flüchtige Fettsäuren sowie pH-Wertänderungen untersucht. Es konnte festgestellt werden, dass die gemessenen Werte nicht die alleinige Ursache für das Absterben der Erreger sind, vielmehr wird eine zusätzliche bakterizide Wirkung durch eine mutmaßliche Bildung von Bakteriozinen in Betracht gezogen. Die parasitizide Wirkung wird auf die physikalischen Bedingungen der Fermentation zurückgeführt.
Die methodischen Grundlagen basieren auf Analysen mittels zahlreicher klassisch-kultureller Verfahren, wie z. B. der Lebendkeimzahlbestimmung. Darüber hinaus findet die MALDI-TOF-Massenspektrometrie und die klassische PCR in Kombination mit der Gradienten-Gelelektrophorese Anwendung, um kultivierbare Bakterienfloren zu beschreiben bzw. nicht kultivierbare Bakterienfloren stichprobenartig zu erfassen.
Neben den Aspekten der Hygienisierung wird zudem die Eignung der Methode für die landwirtschaftliche Nutzung berücksichtigt. Dies findet sich insbesondere in der Komposition des zu fermentierenden Materials wieder, welches für die verstärkte Humusakkumulation im Ackerboden optimiert wurde. Darüber hinaus wird die Masseverlustbilanz während der milchsauren Fermentation mit denen der Kompostierung sowie der Verarbeitung in der Biogasanlage verglichen und als positiv bewertet, da sie mit insgesamt 2,45 % sehr deutlich unter den bisherigen Alternativen liegt (73, 138, 458). Weniger Verluste an organischem Material während der Hygienisierung führen zu einer größeren verwendbaren Düngermenge, die auf Grund ihres organischen Ursprungs zu einer Verstärkung des Humusanteiles im Ackerboden beitragen kann (56, 132).
In der Berufsgruppe der Lehrerinnen und Lehrer besteht eine hohe Prävalenz psychischer und psychosomatischer Erkrankungen. Aus- und Weiterbildungsangebote zur Vermittlung lehrerspezifischer sozialer Kompetenzen spielen eine wichtige Rolle bei der Förderung der Lehrergesundheit. In der vorliegenden Studie wurde das „Lehrer/innen-Coaching nach dem Freiburger Modell“ evaluiert, welches die Kompetenz von Lehrkräften stärken soll, innerhalb der Schule und insbesondere im Unterricht, schwierige interpersonelle Situationen aktiv und konstruktiv zu gestalten. Damit sollen stressbedingte gesundheitliche Belastungen abgebaut und dem Entstehen gravierender psychischer Störungen vorgebeugt werden. In der vorliegenden Arbeit werden zwei modifizierte Versionen dieses Programms erstmalig im Rahmen einer landesweiten Feldstudie untersucht. Die zentralen Evaluationsfragestellungen beziehen sich auf die Effektivität der Intervention als Gesundheitsförderungsmaßnahme (Akzeptanz, Wirksamkeit, Wirksamkeitsvergleich der beiden Interventionsformen im landesweiten Einsatz). Daneben strebt die Studie einen Vergleich mit den Ergebnissen einer Vorgängerstudie sowie die Generierung weiterer Erkenntnisse zum Zusammenhang zwischen Aspekten der sozialen Kompetenz von Lehrkräften und ihrer psychischen Gesundheit an. An der Maßnahme konnten alle baden-württembergischen Lehrerinnen und Lehrer mit einer Berufserfahrung von mindestens 10 Jahren teilnehmen. Für die Untersuchung der Wirksamkeit der Maßnahme und des Wirksamkeitsvergleichs der beiden unterschiedlichen Formen liegt ein quasiexperimentelles Design mit insgesamt zwei Messzeitpunkten vor. In die Auswertung zur Wirksamkeit der Intervention konnten die Daten von den 314 Teilnehmern einbezogen werden. Die Messinstrumente, die in der vorliegenden Studie zur Anwendung kamen, waren der General Health Questionnaire (GHQ-12), das Maslach Burnout Inventory (MBI-D) und die ins Deutsche übersetzte Jefferson Scale of Empathy (JSE) in der an Lehrer adaptierten Form. Die Evaluationsergebnisse zeigen, dass die Teilnahme am „Lehrer/innen-Coaching nach dem Freiburger Modell” mit einer signifikanten Verbesserung der gesundheitsbezogenen abhängigen Variablen einhergeht. Besonders hervorzuheben ist die ausgeprägte Verbesserung der mittels GHQ-12 erfassten psychischen Gesundheit. Das Ergebnis des Prä-Post-Vergleichs der Gesundheitswerte beider Interventionsgruppen bestätigte sich auch im Vergleich zu einer Null-Interventionsgruppe: Entsprechend der Hypothese gab es bei den Teilnehmern eine signifikant stärkere Verbesserung der psychischen Gesundheit als bei den Nicht-Teilnehmern (Null-Interventionsgruppe). Die beiden Interventionsmodi „Kompaktform” und „Kurzform” erwiesen sich im Hinblick auf die Verbesserung der Lehrergesundheit als gleichermaßen wirksam. Zudem zeigen die Ergebnisse der Teilnehmerbefragung, dass die Maßnahme Anklang bei der Zielgruppe fand. Die Akzeptanz durch die Zielgruppe ist für die Wirksamkeit einer auf Freiwilligkeit basierenden verhaltenspräventiven Maßnahme naturgemäß eine essenzielle Voraussetzung. Bei der psychischen Gesundheit der Lehrer bestehen – wie aus weiteren Befunden der Studie ersichtlich – bedeutsame Zusammenhänge zu einer intakten zwischenmenschlichen Beziehung mit den Schülern, einer gelungenen, durch gegenseitige Unterstützung gekennzeichneten Interaktion im Kollegium und einem entsprechend unterstützenden Führungsverhalten der Schulleitung. Dies macht deutlich, welches besondere Gewicht einer gelingenden Beziehungsgestaltung an Schulen und im Unterricht beizumessen ist. Bezüglich der Vorgehensweise in der vorliegenden Untersuchung werden einige methodische Limitationen hinsichtlich des Designs diskutiert. Ergänzend wird im Ausblick der Evaluationsstudie darauf hingewiesen, wie sich durch die Verknüpfung des vorliegenden Programms mit weiteren, auf den Ebenen Verhalten, Verhältnisse und Führung ansetzenden gesundheitspräventiven Maßnahmen, zukünftig die Stärkung der psychischen Gesundheit von Lehrkräften weiter ausbauen ließe.
Polyadenylation is a decisive 3’ end processing step during the maturation of pre-mRNAs. The length of the poly(A) tail has an impact on mRNA stability, localization and translatability. Accordingly, many eukaryotic organisms encode several copies of canonical poly(A) polymerases (cPAPs). The disruption of cPAPs in mammals results in lethality. In plants, reduced cPAP activity is non-lethal. Arabidopsis encodes three nuclear cPAPs, PAPS1, PAPS2 and PAPS4, which are constitutively expressed throughout the plant. Recently, the detailed analysis of Arabidopsis paps1 mutants revealed a subset of genes that is preferentially polyadenylated by the cPAP isoform PAPS1 (Vi et al. 2013). Thus, the specialization of cPAPs might allow the regulation of different sets of genes in order to optimally face developmental or environmental challenges.
To gain insights into the cPAP-based gene regulation in plants, the phenotypes of Arabidopsis cPAPs mutants under different conditions are characterized in detail in the following work. An involvement of all three cPAPs in flowering time regulation and stress response regulation is shown. While paps1 knockdown mutants flower early, paps4 and paps2 paps4 knockout mutants exhibit a moderate late-flowering phenotype. PAPS1 promotes the expression of the major flowering inhibitor FLC, supposedly by specific polyadenylation of an FLC activator. PAPS2 and PAPS4 exhibit partially overlapping functions and ensure timely flowering by repressing FLC and at least one other unidentified flowering inhibitor. The latter two cPAPs act in a novel regulatory pathway downstream of the autonomous pathway component FCA and act independently from the polyadenylation factors and flowering time regulators CstF64 and FY. Moreover, PAPS1 and PAPS2/PAPS4 are implicated in different stress response pathways in Arabidopsis. Reduced activity of the poly(A) polymerase PAPS1 results in enhanced resistance to osmotic and oxidative stress. Simultaneously, paps1 mutants are cold-sensitive. In contrast, PAPS2/PAPS4 are not involved in the regulation of osmotic or cold stress, but paps2 paps4 loss-of-function mutants exhibit enhanced sensitivity to oxidative stress provoked in the chloroplast. Thus, both PAPS1 and PAPS2/PAPS4 are required to maintain a balanced redox state in plants. PAPS1 seems to fulfil this function in concert with CPSF30, a polyadenylation factor that regulates alternative polyadenylation and tolerance to oxidative stress.
The individual paps mutant phenotypes and the cPAP-specific genetic interactions support the model of cPAP-dependent polyadenylation of selected mRNAs. The high similarity of the polyadenylation machineries in yeast, mammals and plants suggests that similar regulatory mechanisms might be present in other organism groups. The cPAP-dependent developmental and physiological pathways identified in this work allow the design of targeted experiments to better understand the ecological and molecular context underlying cPAP-specialization.
Ausprägungen räumlicher Identität in ehemaligen sudetendeutschen Gebieten der Tschechischen Republik
(2014)
Das tschechische Grenzgebiet ist eine der Regionen in Europa, die in der Folge des Zweiten Weltkrieges am gravierendsten von Umbrüchen in der zuvor bestehenden Bevölkerungsstruktur betroffen waren. Der erzwungenen Aussiedlung eines Großteils der ansässigen Bevölkerung folgten die Neubesiedlung durch verschiedenste Zuwanderergruppen sowie teilweise langanhaltende Fluktuationen der Einwohnerschaft. Die Stabilisierung der Bevölkerung stand sodann unter dem Zeichen der sozialistischen Gesellschafts- und Wirtschaftsordnung, die die Lebensweise und Raumwahrnehmung der neuen Einwohner nachhaltig prägte. Die Grenzöffnung von 1989, die politische Transformation sowie die Integration der Tschechischen Republik in die Europäische Union brachten neue demographische und sozioökonomische Entwicklungen mit sich. Sie schufen aber auch die Bedingungen dafür, sich neu und offen auch mit der spezifischen Geschichte des ehemaligen Sudetenlandes sowie mit dem Zustand der gegenwärtigen Gesellschaft in diesem Gebiet auseinanderzusetzen.
Im Rahmen der vorliegenden Arbeit wird anhand zweier Beispielregionen untersucht, welche Raumvorstellungen und Raumbindungen bei der heute in den ehemaligen sudetendeutschen Gebieten ansässigen Bevölkerung vorhanden sind und welche Einflüsse die unterschiedlichen raumstrukturellen Bedingungen darauf ausüben. Besonderes Augenmerk wird auf die soziale Komponente der Ausprägung räumlicher Identität gelegt, das heißt auf die Rolle von Bedeutungszuweisungen gegenüber Raumelementen im Rahmen sozialer Kommunikation und Interaktion. Dies erscheint von besonderer Relevanz in einem Raum, der sich durch eine gewisse Heterogenität seiner Einwohnerschaft hinsichtlich ihres ethnischen, kulturellen beziehungsweise biographischen Hintergrundes auszeichnet. Schließlich wird ermittelt, welche Impulse unter Umständen von einer ausgeprägten räumlichen Identität für die Entwicklung des Raumes ausgehen.
An important contribution of geosciences to the renewable energy production portfolio is the exploration and utilization of geothermal resources. For the development of a geothermal project at great depths a detailed geological and geophysical exploration program is required in the first phase. With the help of active seismic methods high-resolution images of the geothermal reservoir can be delivered. This allows potential transport routes for fluids to be identified as well as regions with high potential of heat extraction to be mapped, which indicates favorable conditions for geothermal exploitation. The presented work investigates the extent to which an improved characterization of geothermal reservoirs can be achieved with the new methods of seismic data processing. The summations of traces (stacking) is a crucial step in the processing of seismic reflection data. The common-reflection-surface (CRS) stacking method can be applied as an alternative for the conventional normal moveout (NMO) or the dip moveout (DMO) stack. The advantages of the CRS stack beside an automatic determination of stacking operator parameters include an adequate imaging of arbitrarily curved geological boundaries, and a significant increase in signal-to-noise (S/N) ratio by stacking far more traces than used in a conventional stack. A major innovation I have shown in this work is that the quality of signal attributes that characterize the seismic images can be significantly improved by this modified type of stacking in particular. Imporoved attribute analysis facilitates the interpretation of seismic images and plays a significant role in the characterization of reservoirs. Variations of lithological and petro-physical properties are reflected by fluctuations of specific signal attributes (eg. frequency or amplitude characteristics). Its further interpretation can provide quality assessment of the geothermal reservoir with respect to the capacity of fluids within a hydrological system that can be extracted and utilized. The proposed methodological approach is demonstrated on the basis on two case studies. In the first example, I analyzed a series of 2D seismic profile sections through the Alberta sedimentary basin on the eastern edge of the Canadian Rocky Mountains. In the second application, a 3D seismic volume is characterized in the surroundings of a geothermal borehole, located in the central part of the Polish basin. Both sites were investigated with the modified and improved stacking attribute analyses. The results provide recommendations for the planning of future geothermal plants in both study areas.
Weltweit streben Anti-Doping Institute danach jene Sportler zu überführen, welche sich unerlaubter Mittel oder Methoden bedienen. Die hierfür notwendigen Testsysteme werden kontinuierlich weiterentwickelt und neue Methoden aufgrund neuer Wirkstoffe der Pharmaindustrie etabliert. Gegenstand dieser Arbeit war es, eine parallele Mehrkomponentenanalyse auf Basis von Antigen-Antikörper Reaktionen zu entwickeln, bei dem es primär um Verringerung des benötigten Probevolumens und der Versuchszeit im Vergleich zu einem Standard Nachweis-Verfahren ging. Neben der Verwendung eines Multiplex Ansatzes und der Mikroarraytechnologie stellten ebenfalls die Genauigkeit aller Messparameter, die Stabilität des Versuchsaufbaus sowie die Performance über einen Einfach-Blind-Ansatz Herausforderungen dar. Die Anforderung an den Multiplex Ansatz, keine falschen Signale trotz ähnlicher Strukturen zu messen, konnte durch die gezielte Kombination von spezifischen Antikörpern realisiert werden. Hierfür wurden neben Kreuzreaktivitätstests auf dem Mikroarray parallel erfolgreich Western Blot Versuche durchgeführt. Jene Antikörper, welche in diesen Versuchen die gesetzten Anforderungen erfüllten, wurden für das Ermitteln der kleinsten nachweisbaren Konzentration verwendet. Über das Optimieren der Versuchsbedingungen konnte unter Verwendung von Tween in der Waschlösung sowohl auf Glas als auch auf Kunststoff die Hintergrundfluoreszenz reduziert und somit eine Steigerung des Signal/Hintergrundverhältnisses erreicht werden. In den Versuchen zu Ermittlung der Bestimmungsgrenze wurde für das humane Choriongonadotropin (hCG-i) eine Konzentration von 10 mU/ml, für dessen beta-Untereinheit (hCG-beta) eine Konzentration von 3,6 mU/ml und für das luteinisierende Hormon (LH) eine Konzentration von 10 mU/ml bestimmt. Den ermittelten Wert im Serum für das hCG-i entspricht dem von der Welt-Anti-Dopin-Agentur (WADA) geforderten Wert in Urin von 5 mU/ml. Neben der Ermittlung von Bestimmungsgrenzen wurden diese hinsichtlich auftretender Matrixeffekte in Serum und Blut gemessen. Wie aus den Versuchen zur Ermittlung von Kreuzreaktivitäten auf dem Mikroarray zu entnehmen ist, lassen sich das LH, das hCG-i und hCG-β ebenfalls in Serum und Blut messen. Die Durchführung einer Performance-Analyse über einem Einfach-Blind-Ansatz mit 130 Serum Proben, wurde ebenfalls über dieses System realisiert. Die ausgewerteten Proben wurden anschließend über eine Grenzwertoptimierungskurve analysiert und die diagnostische Spezifität ermittelt. Für die Messungen des LH konnte eine Sensitivität und Spezifität von 100% erreicht werden. Demnach wurden alle negativen und positiven Proben eindeutig interpretiert. Für das hCG-β konnte ebenfalls eine Spezifität von 100% und eine Sensitivität von 97% erreicht werden. Die hCG-i Proben wurden mit einer Spezifität von 100% und eine Sensitivität von 97,5% gemessen. Um den Nachweis zu erbringen, dass dieser Versuchsaufbau über mehrere Wochen stabile Signale bei Vermessen von identischen Proben liefert, wurde ein über zwölf Wochen angesetzter Stabilitätstest für alle Parameter erfolgreich in Serum und Blut durchgeführt. Zusammenfassend konnte in dieser Arbeit erfolgreich eine Mehrkomponentenanalyse als Multiplex Ansatz auf einem Mikroarray entwickelt werden. Die Durchführung der Performance-Analyse und des Stabilitätstests zeigen bereits die mögliche Einsatzfähigkeit dieses Tests im Kontext einer Dopinganalyse.
Untersuchungen zur pro-inflammatorischen Wirkung von Serum-Amyloid A in glatten Gefäßmuskelzellen
(2014)
It is generally agreed upon that stars typically form in open clusters and stellar associations, but little is known about the structure of the open cluster system. Do open clusters and stellar associations form isolated or do they prefer to form in groups and complexes? Open cluster groups and complexes could verify star forming regions to be larger than expected, which would explain the chemical homogeneity over large areas in the Galactic disk. They would also define an additional level in the hierarchy of star formation and could be used as tracers for the scales of fragmentation in giant molecular clouds? Furthermore, open cluster groups and complexes could affect Galactic dynamics and should be considered in investigations and simulations on the dynamical processes, such as radial migration, disc heating, differential rotation, kinematic resonances, and spiral structure.
In the past decade there were a few studies on open cluster pairs (de La Fuente Marcos & de La Fuente Marcos 2009a,b,c) and on open cluster groups and complexes (Piskunov et al. 2006). The former only considered spatial proximity for the identification of the pairs, while the latter also required tangential velocities to be similar for the members. In this work I used the full set of 6D phase-space information to draw a more detailed picture on these structures. For this purpose I utilised the most homogeneous cluster catalogue available, namely the Catalogue of Open Cluster Data (COCD; Kharchenko et al. 2005a,b), which contains parameters for 650 open clusters and compact associations, as well as for their uniformly selected members. Additional radial velocity (RV) and metallicity ([M/H]) information on the members were obtained from the RAdial Velocity Experiment (RAVE; Steinmetz et al. 2006; Kordopatis et al. 2013) for 110 and 81 clusters, respectively. The RAVE sample was cleaned considering quality parameters and flags provided by RAVE (Matijevič et al. 2012; Kordopatis et al. 2013). To ensure that only real members were included for the mean values, also the cluster membership, as provided by Kharchenko et al. (2005a,b), was considered for the stars cross-matched in RAVE.
6D phase-space information could be derived for 432 out of the 650 COCD objects and I used an adaption of the Friends-of-Friends algorithm, as used in cosmology, to identify potential groupings. The vast majority of the 19 identified groupings were pairs, but I also found four groups of 4-5 members and one complex with 15 members. For the verification of the identified structures, I compared the results to a randomly selected subsample of the catalogue for the Milky Way global survey of Star Clusters (MWSC; Kharchenko et al. 2013), which became available recently, and was used as reference sample. Furthermore, I implemented Monte-Carlo simulations with randomised samples created from two distinguished input distributions for the spatial and velocity parameters. On the one hand, assuming a uniform distribution in the Galactic disc and, on the other hand, assuming the COCD data distributions to be representative for the whole open cluster population.
The results suggested that the majority of identified pairs are rather by chance alignments, but the groups and the complex seemed to be genuine. A comparison of my results to the pairs, groups and complexes proposed in the literature yielded a partial overlap, which was most likely because of selection effects and different parameters considered. This is another verification for the existence of such structures.
The characteristics of the found groupings favour that members of an open cluster grouping originate from a common giant molecular cloud and formed in a single, but possibly sequential, star formation event. Moreover, the fact that the young open cluster population showed smaller spatial separations between nearest neighbours than the old cluster population indicated that the lifetime of open cluster groupings is most likely comparable to that of the Galactic open cluster population itself. Still even among the old open clusters I could identify groupings, which suggested that the detected structure could be in some cases more long lived as one might think.
In this thesis I could only present a pilot study on structures in the Galactic open cluster population, since the data sample used was highly incomplete. For further investigations a far more complete sample would be required. One step in this direction would be to use data from large current surveys, like SDSS, RAVE, Gaia-ESO and VVV, as well as including results from studies on individual clusters. Later the sample can be completed by data from upcoming missions, like Gaia and 4MOST. Future studies using this more complete open cluster sample will reveal the effect of open cluster groupings on star formation theory and their significance for the kinematics, dynamics and evolution of the Milky Way, and thereby of spiral galaxies.
התזות של העבודה
תקופת חז"ל
1. איסור הנישואין מתייחס לשתי נשים – מעוברת ומנקת, ובהתאם לסוגיה הסתמאית בבבלי יבמות, מדובר באיסור שטעמו אחד. למרות תפיסה מקובלת זו, להערכתנו בהלכה הקדומה מדובר היה בשני איסורים שונים: איסור נישואי מעוברת חברו ואיסור נישואי מנקת שמת בעלה.
למסקנה זו הגענו כתוצאה משורה של ראיות:
א. הסוגיה הסתמאית במסכת יבמות מעוררת קשיים רבים (אשר פורטו בעמ' לעבודתנו). קשיים אלה והעובדה כי במחקר המודרני נהוג לשייך סוגיות סתמאיות לסוף תקופת האמוראים ואף לאחר מכן, הביאו אותנו לשער כי סוגיה זו משקפת הצגה מאוחרת של טעם הדין. טעם שונה של הדין מצוי במקורות תנאיים, והוא המשקף כנראה את טעמו הקדום של הדין .
ב. שניים מתוך שלושת המקורות התנאיים, עוסקים האחד רק במנקת והשני רק במעוברת, ולא בשתי הנשים יחד.
ג. ניתוח הלשון של המקורות, מצביע על שורה של שינויים משמעותיים, אשר יש בהם כדי ללמד כי מדובר באיסורים שונים.
2. בהלכה הקדומה נתפס איסור נישואי "מעוברת חברו" כאיסור חמור, והוא הוסמך לפסוקים מהתנ"ך שאסרו הסגת גבול. בשלב מאוחר יותר בתקופת התנאים האיסור פורש ככזה שנועד להבטיח את הנקתו של הילד, צורפה לאיסור הקביעה כי אין לשאת אלמנה מנקת, והיחס לאיסור היה מקל יותר.
למסקנה זו הגענו כתוצאה מהדברים הבאים:
א. בניגוד למקורות תנאיים שנקטו בגישה מקלה במגוון עניינים, ישנם מספר מקורות המציגים גישה מחמירה – לפיה מי שעבר ונשא אלמנה בניגוד לאיסור, "יוציא ולא יחזיר עולמית".
ב. משורה של מקורות שעסקו בדין סוטה, ניכר כי העמדה ההלכתית הקדומה נקטה בגישה לפיה מי שעבר ונשא אלמנה בניגוד לדין והוא חושד כי אשתו סטתה, אינו משקה אותה מי סוטה, שכן היא אסורה עליו עולמית. גישה מקלה יותר, לפיה יכול הוא להפרישה ולהחזירה לאחר זמן ולכן יש טעם בהשקאת הסוטה במקרה כגון זה, התגבשה בספרות התנאית רק בשלב מאוחר יותר. במקביל וללא קשר לדיני סוטה, התפתחה אצל התנאים גישה מקלה, לפיה ישנם חריגים משמעותיים לאיסור נישואי האלמנה (כגון: כאשר הילד נגמל; כאשר הילד נמסר למנקת).
ג. מקור תנאי שעסק רק במעוברת חברו ולא במנקת שמת בעלה, נקט בגישה המחמירה ("יוציא ולא יחזיר עולמית") ולא הזכיר כלל קיומה של גישה מקלה ("יכול הוא להפרישה ולהחזירה לאחר זמן".
ד. מקורות תנאיים בספרות ארץ-ישראלית (מדרש הלכה, התוספתא וברייתא בירושלמי), ראו במי שעבר ונשא כמי שעבר על איסור הנמסך לפסוקים מהתנ"ך (ספר דברים וספר משלי) והאוסרים הסגת גבול. הצענו להבין את הסגת הגבול כמתארת מסגרת שייכות, ולפיה אלמנה שייכת לבעלה המנוח וזאת בכל הקושר לחובתה להבטחת זרעו.
ה. חוקרים (כגון י' גילת) הצביעו על תופעה המאפיינת את המעבר מההלכה הקדומה אל משנתם של התנאים לאחר החורבן: מעבר מגישה מחמירה אשר אינה מכירה בהבחנה בין דין שמעמדו מדאורייתא לדין שמעמדו מדרבנן, אל גישה מקלה יותר המשתלבת עם הנמקה שונה של האיסורים הקדומים והעמדתם במעמד של דרבנן בלבד.
ו. אנו משערים, למרות שהדבר אינו בר הוכחה חותכת, כי תהליך דומה פקד את הדין בו אנו עוסקים: בהלכה הקדומה נאסרה מעוברת חברו, מכוח הפסוק המקראי האוסר על הסגת גבול. איסור זה נחשב כאיסור מהתורה, ולכן היה בו כדי לדחות את מצוות השקאת הסוטה. בשלב מאוחר יותר, כאשר המוסג השגת גבול בכל הנוגע לאלמנה נראה פחות מתאים (בין השאר, הואיל ואלמנה "קונה עצמה" במיתת הבעל – כדברי המשנה בקידושין), הוצע טעם חדש לאיסור – הפגיעה האפשרית בחלב האם. לאור הנמקה זו, חבר אל איסור נישואי מעוברת חברו, גם האיסור לשאת מנקת שמת בעלה, והאיסור בכללותו נתפס בקרב התנאים כאיסור מדרבנן בלבד ושחומרתו קלה יותר. בשלב זה, הפכה הדעה לפיה מי שעבר ונשא "יוציא ולא יחזיר עולמית" לדעת יחיד בלבד(דעת ר' מאיר), ואילו הרבים קבעו כי "יכול הוא להפרישה ולהחזירה לאחר זמן".
3. בתום תקופת האמוראים ואולי אף בתקופה הסבוראית, הוחלט לאמץ את העמדות המחמירות יותר בכל הנוגע לאיסור הנישואין. נקבע כי מלבד מקרה של מות הילד, אין לאיסור חריגים, והאיסור חל גם כאשר הילד כבר אינו יונק. כמו כן נקבע כי משך ההמתנה הנדרש הוא 24 חודשים מהמועד בו נולד הילד. קביעות אלה משקפות הכרעה לאמץ מגמה מחמירה, מתוך מכלול הדעות אשר אפשרו גם אימוץ גישה מקלה יותר.
כפי שהראנו בעבודתנו , ההכרעה לכיוון המחמיר התקבלה ככל הנראה בתקופה הסבוראית. הכרעה זו אינה מובנת מאליה, שכן היו מקורות תנאיים ואמוראיים על בסיסם ניתן היה לקבוע כי יש לאמץ גישה מקלה יותר. לדוגמא, דעת בית הלל ודעת ר' יהודה הייתה כי משך האיסור הוא 18 חודשים בלבד. דעת רשב"ג הייתה כי ניתן לקצר את האיסור בשלושה חודשים נוספים, כך באיסור יהיה למשך 15 חודשים בלבד. לאור זאת, קביעת ההלכתא הסבוראית כי משך ההמתנה הוא 24 חודשים – אינה מובנת מאליה. למרות שאין ביכולתנו להצביע בוודאות על הסבר מדוע אומצה הגישה המחמירה, בעבודתנו הצבענו על ההחמרה במצב היהודים בתקופה הרלבנטית, כרקע אשר עשוי להשתלב עם אימוץ הגישה המחמירה .
תקופת הגאונים
4. בתקופת הגאונים נשמרו חילוקי הדעות בין בני בבל לבני ארץ ישראל, אשר מקורם בהבדלים בין התלמוד הבבלי לתלמוד הירושלמי. הבדלים אלה נוגעים לשאלה מה הדין במקרה בו מת הילד, ולטענתנו גם אודות השאלה האם מי שעבר ונשא יחויב לתת לאשתו גט או שדי בהפרשה בלבד. בסופו של דבר, גאוני בבל הביאו לכך שעמדת הבבלי היא שהתקבלה בעניינים אלה בקרב פוסקי ההלכה.
בעבודתנו עמדנו על היתר שחודש בתקופת הגאונים, ועל שלבים משעורים בהתפתחותו.
תקופת הראשונים
5. בעבודתנו עמדנו על המגמה שאפיינה את פסיקת ההלכה בדין בו אנו עוסקים בתקופת הראשונים. ניסינו להסביר מדוע נעשו ניסיונות לגבש הקלות באיסור הנישואין, ומדוע בסופו של דבר, לדעת רוב הראשונים וכפי שההלכה סוכמה בשלחן ערוך, הגישות המחמירות הן שאומצו. על עניינים אלו.
6. הרחבת היקף פריסתו של האיסור: בניגוד למקורות מתקופת חז"ל מהם נראה כי האיסור חל רק על אלמנה, בתקופת הראשונים נקבע כי האיסור חל גם על גרושה שיש לה ילד מנישואיה הקודמים, וגם על רווקה שילדה ילד מחוץ למסגרת הנישואין. קביעות אלה הביאו להרחבה ניכרת של המקרים בהם חל האיסור.
בעבודתנו עמדנו על הגישות השונות שהיו בסוגיה זו: אודות גרושה אודות מי שילדה בזנות .
עמדנו על כך שישנה קירבה בין שני הנימוקים השונים שהוזכרו בראשית דרכה של ההלכה על טעם האיסור, לבין המחלוקת בין הדעות השונות בשאלת תחולת האיסור על גרושה ועל מי שילדה בזנות. בהתאם לגישה שראתה באיסור משום הסגת גבולו של הבעל הראשון, אין מקום להחלת האיסור כאשר הנישואין הסתיימו בגירושין או כאשר הילד נולד מבלי שהיה קשר נישואין בין הוריו. מנגד, בהתאם לטעם שפורט בבבלי ואשר התמקד בנזק שעלול להיגרם לילד, חשש זה רלבנטי ללא קשר לטיב היחסים בין ההורים ומשכך יש מקום להחיל את איסור הנישואין גם על גרושה וגם על מי שילדה בזנות.
7. פרשיית ר' יעקב מקרקוב והשפעתה על עמדת חכמי ספרד: ר' יעקב מקרקוב סבר כי ניתן לייצר חריגים לאיסור, וזאת על-ידי מסירת הילד למנקת בשכר ועיצוב מנגנון אשר יבטיח שהמנקת לא תפר את התחייבותה להניק את הילד. עמדה זו נדחתה בחריפות על-ידי חכמי אשכנז, אולם נראה כי היא הייתה מקובלת על הרשב"א. כאשר הרא"ש היגר מאשכנז לספרד, הוא הוביל שינוי בתפיסה הספרדית ואימוץ הגישה המחמירה שמקורה באשכנז . העמדות המקלות בסוגיה זו, ככל הנראה צונזרו באופן כה יעיל, עד כי נראה שר' יוסף קארו מחבר השלחן ערוך, לא היה מודע לקיומן.
8. יחסו של הרא"ש להיתר שקבעו הגאונים: עמדנו בפירוט על תהליך העולה ממכלול יצירותיו של הרא"ש: דחיה של היתר שיוחס לגאונים; לאחר מכן אימוץ מהוסס בשעת הדחק של ההיתר; ובסופו של דבר אימוץ היתר רחב יותר העומד בפני עצמו ואינו נשען על משנתם של הגאונים. בהמשך, עמדנו על האופן בו התייחסו חכמי ספרד להיתר הרחב שקבע הרא"ש.
סוגיה זו ממחישה את יחסם השונה של חכמי ספרד וחכמי אשכנז אל תורתם של גאוני בבל, וכן היחס השונה של חכמי ספרד וחכמי אשכנז ללגיטימיות החדשנות ההלכתית. בסוגיה זו, בניגוד לסוגיה שנדונה בסעיף הקודם, הרא"ש גילה גמישות, והסכים להתקרב לעמדת חכמי ספרד (על השערתנו אודות ההסבר לכך).
העת החדשה
9. בעת החדשה, בעקבות קיצור משך ההנקה המקובל, נוצרו שני זרמים מרכזיים ביחס אל איסור הנישואין: הגישה המחמירה מבית מדרשו של החת"ם סופר, והגישה המקלה. הגישה המחמירה מבית מדרשו של החת"ם סופר, הסכימה להתיר את איסור הנישואין, רק כאשר היה חשש שאם איסור הנישואין לא יבוטל, הילד עלול לצאת ממסגרת החיים הדתיים. גישתו המחמירה של החת"ם סופר, הושפעה להערכתנו מהעובדה שאחד מראשוני תנועת הרפורמה, ר' אהרן חורין, טען כי יש לבטל את איסור הנישואין . על-מנת לחזק את תוקפו של האיסור, תלמידו של החת"ם סופר – המהר"ם שיק, טען כי מדובר באיסור מהתורה.
10. הגישה המקלה: גישה זו מורכבת מפסקי הלכה של פוסקים שונים, אשר הסכימו לאמץ הקלות באיסור הנישואין (לפירוט ההקלות העיקריות). הקלות אלה משקפות את גמישותו הרבה של הטקסט המתפרש. אותם טקסטים עצמם שהובנו בעבר באופן מחמיר, פורשו לפתע באופן מקל הרבה יותר. אנו מעריכים כי שינוי הפרשנות נבע משינוי המציאות הסובבת.
11. גם בעלי הגישה המקלה, הושפעו מעמדותיו של החת"ם סופר. השפעה זו באה לידי ביטוי בכך שבעלי הגישה המקלה היו מוכנים לאמץ גישות מקלות שנדחו על-ידי פוסקי ההלכה בעבר, אולם בדרך כלל הם לא היו מוכנים להכיר בצורך בשינוי דרמטי במעמדו של הדין, לאור שינוי המציאות. להערכתנו, עמדה שמרנית זו מובילה לתוצאות בלתי ראויות, והיא אינה משקפת בחינה אמיצה של מידת הרלבנטיות של איסור הנישואין למציאות החיים היהודיים בעשורים האחרונים.
Der Bittergeschmack dient Säugern vermutlich zur Wahrnehmung und Vermeidung toxischer Substanzen. Bitterstoffe können jedoch auch gesund sein oder werden oft bereitwillig mit der Nahrung aufgenommen. Ob sie geschmacklich unterschieden werden können, ist allerdings umstritten. Detektiert werden Bitterstoffe von oralen Bittergeschmacksrezeptoren, den TAS2R (human) bzw. Tas2r (murin). In der Literatur gibt es aber immer mehr Hinweise darauf, dass überdies Tas2r nicht nur in extragustatorischen Organen exprimiert werden, sondern dort auch wichtige Aufgaben erfüllen könnten, was wiederum die Aufklärung ihrer noch nicht vollständig entschlüsselten Funktionsweisen erfordert. So ist noch unbekannt, ob alle bisher als funktionell identifizierten Tas2r wirklich gustatorische Funktionen erfüllen.
Im Rahmen der Charakterisierung neu generierter, im Locus des Bittergeschmacksrezeptors Tas2r131 genetisch modifizierter Mauslinien, wurde in vorliegender Arbeit die gustatorische sowie extragustatorische Expression von Tas2r131 untersucht. Dass Tas2r131 nicht nur in Pilzpapillen, Wall- und Blätterpapillen (VP+FoP), Gaumen, Ductus nasopalatinus, Vomeronasalorgan und Kehldeckel, sondern auch in Thymus, Testes und Nebenhodenkopf, in Gehirnarealen sowie im Ganglion geniculatum nachgewiesen wurde, bildete die Grundlage für weiterführende Studien. Die vorliegende Arbeit zeigt außerdem, dass Tas2r108, Tas2r126, Tas2r135, Tas2r137 und Tas2r143 in Blut exprimiert werden, was auf eine heterogene Funktion der Tas2r hindeutet. Dass zusätzlich erstmals die Expression aller 35 als funktionell beschriebenen Tas2r im gustatorischen VP+FoP-Epithel von C57BL/6-Mäusen nachgewiesen wurde, verweist auf deren Relevanz als funktionelle Geschmacksrezeptoren.
Weiter zeigten Untersuchungen zur Aufklärung eines möglichen Bitter-Unterscheidungsvermögens in Geschmackspapillen von Mäusen mit fluoreszenzmarkierten oder ablatierten Tas2r131-Zellen, dass Tas2r131 exprimierende Zellen eine Tas2r-Zellsubpopulation bilden. Darüber hinaus existieren innerhalb der Bitterzellen geordnete Tas2r-Expressionsmuster, die sich nach der chromosomalen Lage ihrer Gene richten. Isolierte Bitterzellen reagieren heterogen auf bekannte Bitterstoffe. Und Mäuse mit ablatierter Tas2r131-Zellpopulation besitzen noch andere Tas2r-Zellen und schmecken damit einige Bitterstoffe kaum noch, andere aber noch sehr gut. Diese Befunde belegen die Existenz verschiedener gustatorischer Tas2r-Zellpopulationen, welche die Voraussetzung bilden, Bitterstoffe heterogen zu detektieren. Ob dies die Grundlage für ein divergierendes Verhalten gegenüber unverträglichen und harmlosen oder gar nützlichen Bitterstoffen darstellt, kann mit Hilfe der dargelegten Tas2r-Expressionsmuster künftig in Verhaltensexperimenten geprüft werden.
Die Bittergeschmackswahrnehmung in Säugetieren stellt sich als ein hochkomplexer Mechanismus dar, dessen Vielschichtigkeit durch die hier neu aufgezeigten heterogenen Tas2r-Expressions- und Funktionsmuster erneut verdeutlicht wird.
The data quality of real-world datasets need to be constantly monitored and maintained to allow organizations and individuals to reliably use their data. Especially, data integration projects suffer from poor initial data quality and as a consequence consume more effort and money. Commercial products and research prototypes for data cleansing and integration help users to improve the quality of individual and combined datasets. They can be divided into either standalone systems or database management system (DBMS) extensions. On the one hand, standalone systems do not interact well with DBMS and require time-consuming data imports and exports. On the other hand, DBMS extensions are often limited by the underlying system and do not cover the full set of data cleansing and integration tasks.
We overcome both limitations by implementing a concise set of five data cleansing and integration operators on the parallel data analytics platform Stratosphere. We define the semantics of the operators, present their parallel implementation, and devise optimization techniques for individual operators and combinations thereof. Users specify declarative queries in our query language METEOR with our new operators to improve the data quality of individual datasets or integrate them to larger datasets. By integrating the data cleansing operators into the higher level language layer of Stratosphere, users can easily combine cleansing operators with operators from other domains, such as information extraction, to complex data flows. Through a generic description of the operators, the Stratosphere optimizer reorders operators even from different domains to find better query plans.
As a case study, we reimplemented a part of the large Open Government Data integration project GovWILD with our new operators and show that our queries run significantly faster than the original GovWILD queries, which rely on relational operators. Evaluation reveals that our operators exhibit good scalability on up to 100 cores, so that even larger inputs can be efficiently processed by scaling out to more machines. Finally, our scripts are considerably shorter than the original GovWILD scripts, which results in better maintainability of the scripts.
Characterization of drought tolerance in potato cultivars for identification of molecular markers
(2014)
Following the principles of green chemistry, a simple and efficient synthesis of functionalised imidazolium zwitterionic compounds from renewable resources was developed based on a modified one-pot Debus-Radziszewski reaction. The combination of different carbohydrate-derived 1,2-dicarbonyl compounds and amino acids is a simple way to modulate the properties and introduce different functionalities. A representative compound was assessed as an acid catalyst, and converted into acidic ionic liquids by reaction with several strong acids. The reactivity of the double carboxylic functionality was explored by esterification with long and short chain alcohols, as well as functionalised amines, which led to the straightforward formation of surfactant-like molecules or bifunctional esters and amides. One of these di-esters is currently being investigated for the synthesis of poly(ionic liquids). The functionalisation of cellulose with one of the bifunctional esters was investigated and preliminary tests employing it for the functionalisation of filter papers were carried out successfully. The imidazolium zwitterions were converted into ionic liquids via hydrothermal decarboxylation in flow, a benign and scalable technique. This method provides access to imidazolium ionic liquids via a simple and sustainable methodology, whilst completely avoiding contamination with halide salts. Different ionic liquids can be generated depending on the functionality contained in the ImZw precursor. Two alanine-derived ionic liquids were assessed for their physicochemical properties and applications as solvents for the dissolution of cellulose and the Heck coupling.
Monoclonal antibodies (mAbs) are engineered immunoglobulins G (IgG) used for more than 20 years as targeted therapy in oncology, infectious diseases and (auto-)immune disorders. Their protein nature greatly influences their pharmacokinetics (PK), presenting typical linear and non-linear behaviors.
While it is common to use empirical modeling to analyze clinical PK data of mAbs, there is neither clear consensus nor guidance to, on one hand, select the structure of classical compartment models and on the other hand, interpret mechanistically PK parameters. The mechanistic knowledge present in physiologically-based PK (PBPK) models is likely to support rational classical model selection and thus, a methodology to link empirical and PBPK models is desirable. However, published PBPK models for mAbs are quite diverse in respect to the physiology of distribution spaces and the parameterization of the non-specific elimination involving the neonatal Fc receptor (FcRn) and endogenous IgG (IgGendo). The remarkable discrepancy between the simplicity of biodistribution data and the complexity of published PBPK models translates in parameter identifiability issues.
In this thesis, we address this problem with a simplified PBPK model—derived from a hierarchy of more detailed PBPK models and based on simplifications of tissue distribution model. With the novel tissue model, we are breaking new grounds in mechanistic modeling of mAbs disposition: We demonstrate that binding to FcRn is indeed linear and that it is not possible to infer which tissues are involved in the unspecific elimination of wild-type mAbs. We also provide a new approach to predict tissue partition coefficients based on mechanistic insights: We directly link tissue partition coefficients (Ktis) to data-driven and species-independent published antibody biodistribution coefficients (ABCtis) and thus, we ensure the extrapolation from pre-clinical species to human with the simplified PBPK model. We further extend the simplified PBPK model to account for a target, relevant to characterize the non-linear clearance due to mAb-target interaction.
With model reduction techniques, we reduce the dimensionality of the simplified PBPK model to design 2-compartment models, thus guiding classical model development with physiological and mechanistic interpretation of the PK parameters. We finally derive a new scaling approach for anatomical and physiological parameters in PBPK models that translates the inter-individual variability into the design of mechanistic covariate models with direct link to classical compartment models, specially useful for PK population analysis during clinical development.
Protein-metal coordination complexes are well known as active centers in enzymatic catalysis, and to contribute to signal transduction, gas transport, and to hormone function. Additionally, they are now known to contribute as load-bearing cross-links to the mechanical properties of several biological materials, including the jaws of Nereis worms and the byssal threads of marine mussels. The primary aim of this thesis work is to better understand the role of protein-metal cross-links in the mechanical properties of biological materials, using the mussel byssus as a model system. Specifically, the focus is on histidine-metal cross-links as sacrificial bonds in the fibrous core of the byssal thread (Chapter 4) and L-3,4-dihydroxyphenylalanine (DOPA)-metal bonds in the protective thread cuticle (Chapter 5).
Byssal threads are protein fibers, which mussels use to attach to various substrates at the seashore. These relatively stiff fibers have the ability to extend up to about 100 % strain, dissipating large amounts of mechanical energy from crashing waves, for example. Remarkably, following damage from cyclic loading, initial mechanical properties are subsequently recovered by a material-intrinsic self-healing capability. Histidine residues coordinated to transition metal ions in the proteins comprising the fibrous thread core have been suggested as reversible sacrificial bonds that contribute to self-healing; however, this remains to be substantiated in situ. In the first part of this thesis, the role of metal coordination bonds in the thread core was investigated using several spectroscopic methods. In particular, X-ray absorption spectroscopy (XAS) was applied to probe the coordination environment of zinc in Mytilus californianus threads at various stages during stretching and subsequent healing. Analysis of the extended X-ray absorption fine structure (EXAFS) suggests that tensile deformation of threads is correlated with the rupture of Zn-coordination bonds and that self-healing is connected with the reorganization of Zn-coordination bond topologies rather than the mere reformation of Zn-coordination bonds. These findings have interesting implications for the design of self-healing metallopolymers.
The byssus cuticle is a protective coating surrounding the fibrous thread core that is both as hard as an epoxy and extensible up to 100 % strain before cracking. It was shown previously that cuticle stiffness and hardness largely depend on the presence of Fe-DOPA coordination bonds. However, the byssus is known to concentrate a large variety of metals from seawater, some of which are also capable of binding DOPA (e.g. V). Therefore, the question arises whether natural variation of metal composition can affect the mechanical performance of the byssal thread cuticle. To investigate this hypothesis, nanoindentation and confocal Raman spectroscopy were applied to the cuticle of native threads, threads with metals removed (EDTA treated), and threads in which the metal ions in the native tissue were replaced by either Fe or V. Interestingly, replacement of metal ions with either Fe or V leads to the full recovery of native mechanical properties with no statistical difference between each other or the native properties. This likely indicates that a fixed number of metal coordination sites are maintained within the byssal thread cuticle – possibly achieved during thread formation – which may provide an evolutionarily relevant mechanism for maintaining reliable mechanics in an unpredictable environment.
While the dynamic exchange of bonds plays a vital role in the mechanical behavior and self-healing in the thread core by allowing them to act as reversible sacrificial bonds, the compatibility of DOPA with other metals allows an inherent adaptability of the thread cuticle to changing circumstances. The requirements to both of these materials can be met by the dynamic nature of the protein-metal cross-links, whereas covalent cross-linking would fail to provide the adaptability of the cuticle and the self-healing of the core. In summary, these studies of the thread core and the thread cuticle serve to underline the important and dynamic roles of protein-metal coordination in the mechanical function of load-bearing protein fibers, such as the mussel byssus.
The quantitative descriptions of the state of stress in the Earth’s crust, and spatial-temporal stress changes are of great importance in terms of scientific questions as well as applied geotechnical issues. Human activities in the underground (boreholes, tunnels, caverns, reservoir management, etc.) have a large impact on the stress state. It is important to assess, whether these activities may lead to (unpredictable) hazards, such as induced seismicity. Equally important is the understanding of the in situ stress state in the Earth’s crust, as it allows the determination of safe well paths, already during well planning. The same goes for the optimal configuration of the injection- and production wells, where stimulation for artificial fluid path ways is necessary.
The here presented cumulative dissertation consists of four separate manuscripts, which are already published, submitted or will be submitted for peer review within the next weeks. The main focus is on the investigation of the possible usage of geothermal energy in the province Alberta (Canada). A 3-D geomechanical–numerical model was designed to quantify the contemporary 3-D stress tensor in the upper crust. For the calibration of the regional model, 321 stress orientation data and 2714 stress magnitude data were collected, whereby the size and diversity of the database is unique. A calibration scheme was developed, where the model is calibrated versus the in situ stress data stepwise for each data type and gradually optimized using statistically test methods. The optimum displacement on the model boundaries can be determined by bivariate linear regression, based on only three model runs with varying deformation ratio. The best-fit model is able to predict most of the in situ stress data quite well. Thus, the model can provide the full stress tensor along any chosen virtual well paths. This can be used to optimize the orientation of horizontal wells, which e.g. can be used for reservoir stimulation. The model confirms regional deviations from the average stress orientation trend, such as in the region of the Peace River Arch and the Bow Island Arch.
In the context of data compilation for the Alberta stress model, the Canadian database of the World Stress Map (WSM) could be expanded by including 514 new data records. This publication of an update of the Canadian stress map after ~20 years with a specific focus on Alberta shows, that the maximum horizontal stress (SHmax) is oriented southwest to northeast over large areas in Northern America. The SHmax orientation in Alberta is very homogeneous, with an average of about 47°. In order to calculate the average SHmax orientation on a regular grid as well as to estimate the wave-length of stress orientation, an existing algorithm has been improved and is applied to the Canadian data. The newly introduced quasi interquartile range on the circle (QIROC) improves the variance estimation of periodic data, as it is less susceptible to its outliers.
Another geomechanical–numerical model was built to estimate the 3D stress tensor in the target area ”Nördlich Lägern” in Northern Switzerland. This location, with Opalinus clay as a host rock, is a potential repository site for high-level radioactive waste. The performed modelling aims to investigate the sensitivity of the stress tensor on tectonic shortening, topography, faults and variable rock properties within the Mesozoic sedimentary stack, according to the required stability needed for a suitable radioactive waste disposal site. The majority of the tectonic stresses caused by the far-field shortening from the South are admitted by the competent rock units in the footwall and hanging wall of the argillaceous target horizon, the Upper Malm and Upper Muschelkalk. Thus, the differential stress within the host rock remains relatively low. East-west striking faults release stresses driven by tectonic shortening. The purely gravitational influence by the topography is low; higher SHmax magnitudes below topographical depression and lower values below hills are mainly observed near the surface. A complete calibration of the model is not possible, as no stress magnitude data are available for calibration, yet. The collection of this data will begin in 2015; subsequently they will be used to adjust the geomechanical–numerical model again.
The third geomechanical–numerical model investigates the stress variation in an ultra-deep gold mine in South Africa. This reservoir model is spatially one order of magnitude smaller than the previous local model from Northern Switzerland. Here, the primary focus is to investigate the hypothesis that the Mw 1.9 earthquake on 27 December 2007 was induced by stress changes due to the mining process. The Coulomb failure stress change (DeltaCFS) was used to analyse the stress change. It confirmed that the seismic event was induced by static stress transfer due to the mining progress. The rock was brought closer to failure on the derived rupture plane by stress changes of up to 1.5–15MPa, in dependence of the DeltaCFS analysis type. A forward modelling of a generic excavation scheme reveals that with decreasing distance to the dyke the DeltaCFS values increase significantly. Hence, even small changes in the mining progress can have a significant impact on the seismic hazard risk, i.e. the change of the occurrence probability to induce a seismic event of economic concern.
Inferring gene regulatory networks and cellular phases from time-resolved transcriptomics data
(2014)
The Epoch of Reionization marks after recombination the second major change in the ionization state of the universe, going from a neutral to an ionized state. It starts with the appearance of the first stars and galaxies; a fraction of high-energy photons emitted from galaxies permeate into the intergalactic medium (IGM) and gradually ionize the hydrogen, until the IGM is completely ionized at z~6 (Fan et al., 2006). While the progress of reionization is driven by galaxy evolution, it changes the ionization and thermal state of the IGM substantially and affects subsequent structure and galaxy formation by various feedback mechanisms.
Understanding this interaction between reionization and galaxy formation is further impeded by a lack of understanding of the high-redshift galactic properties such as the dust distribution and the escape fraction of ionizing photons. Lyman Alpha Emitters (LAEs) represent a sample of high-redshift galaxies that are sensitive to all these galactic properties and the effects of reionization.
In this thesis we aim to understand the progress of reionization by performing cosmological simulations, which allows us to investigate the limits of constraining reionization by high-redshift galaxies as LAEs, and examine how galactic properties and the ionization state of the IGM affect the visibility and observed quantities of LAEs and Lyman Break galaxies (LBGs).
In the first part of this thesis we focus on performing radiative transfer calculations to simulate reionization. We have developed a mapping-sphere-scheme, which, starting from spherically averaged temperature and density fields, uses our 1D radiative transfer code and computes the effect of each source on the IGM temperature and ionization (HII, HeII, HeIII) profiles, which are subsequently mapped onto a grid. Furthermore we have updated the 3D Monte-Carlo radiative transfer pCRASH, enabling detailed reionization simulations which take individual source characteristics into account.
In the second part of this thesis we perform a reionization simulation by post-processing a smoothed-particle hydrodynamical (SPH) simulation (GADGET-2) with 3D radiative transfer (pCRASH), where the ionizing sources are modelled according to the characteristics of the stellar populations in the hydrodynamical simulation. Following the ionization fractions of hydrogen (HI) and helium (HeII, HeIII), and temperature in our simulation, we find that reionization starts at z~11 and ends at z~6, and high density regions near sources are ionized earlier than low density regions far from sources.
In the third part of this thesis we couple the cosmological SPH simulation and the radiative transfer simulations with a physically motivated, self-consistent model for LAEs, in order to understand the importance of the ionization state of the IGM, the escape fraction of ionizing photons from galaxies and dust in the interstellar medium (ISM) on the visibility of LAEs. Comparison of our models results with the LAE Lyman Alpha (Lya) and UV luminosity functions at z~6.6 reveals a three-dimensional degeneracy between the ionization state of the IGM, the ionizing photons escape fraction and the ISM dust distribution, which implies that LAEs act not only as tracers of reionization but also of the ionizing photon escape fraction and of the ISM dust distribution. This degeneracy does not even break down when we compare simulated with observed clustering of LAEs at z~6.6. However, our results show that reionization has the largest impact on the amplitude of the LAE angular correlation functions, and its imprints are clearly distinguishable from those of properties on galactic scales. These results show that reionization cannot be constrained tightly by exclusively using LAE observations. Further observational constraints, e.g. tomographies of the redshifted hydrogen 21cm line, are required.
In addition we also use our LAE model to probe the question when a galaxy is visible as a LAE or a LBG. Within our model galaxies above a critical stellar mass can produce enough luminosity to be visible as a LBG and/or a LAE. By finding an increasing duty cycle of LBGs with Lya emission as the UV magnitude or stellar mass of the galaxy rises, our model reveals that the brightest (and most massive) LBGs most often show Lya emission.
Predicting the Lya equivalent width (Lya EW) distribution and the fraction of LBGs showing Lya emission at z~6.6, we reproduce the observational trend of the Lya EWs with UV magnitude. However, the Lya EWs of the UV brightest LBGs exceed observations and can only be reconciled by accounting for an increased Lya attenuation of massive galaxies, which implies that the observed Lya brightest LAEs do not necessarily coincide with the UV brightest galaxies. We have analysed the dependencies of LAE observables on the properties of the galactic and intergalactic medium and the LAE-LBG connection, and this enhances our understanding of the nature of LAEs.
The purpose of this thesis is to develop an automated inversion scheme to derive point and finite source parameters for weak earthquakes, here intended with the unusual meaning of earthquakes with magnitudes at the limit or below the bottom magnitude threshold of standard source inversion routines. The adopted inversion approaches entirely rely on existing inversion software, the methodological work mostly targeting the development and tuning of optimized inversion flows. The resulting inversion scheme is tested for very different datasets, and thus allows the discussion on the source inversion problem at different scales. In the first application, dealing with mining induced seismicity, the source parameters determination is addressed at a local scale, with source-sensor distance of less than 3 km. In this context, weak seismicity corresponds to event below magnitude MW 2.0, which are rarely target of automated source inversion routines. The second application considers a regional dataset, namely the aftershock sequence of the 2010 Maule earthquake (Chile), using broadband stations at regional distances, below 300 km. In this case, the magnitude range of the target aftershocks range down to MW 4.0. This dataset is here considered as a weak seismicity case, since the analysis of such moderate seismicity is generally investigated only by moment tensor inversion routines, with no attempt to resolve source duration or finite source parameters. In this work, automated multi-step inversion schemes are applied to both datasets with the aim of resolving point source parameters, both using double couple (DC) and full moment tensor (MT) models, source duration and finite source parameters. A major result of the analysis of weaker events is the increased size of resulting moment tensor catalogues, which interpretation may become not trivial. For this reason, a novel focal mechanism clustering approach is used to automatically classify focal mechanisms, allowing the investigation of the most relevant and repetitive rupture features. The inversion of the mining induced seismicity dataset reveals the repetitive occurrence of similar rupture processes, where the source geometry is controlled by the shape of the mined panel. Moreover, moment tensor solutions indicate a significant contribution of tensile processes. Also the second application highlights some characteristic geometrical features of the fault planes, which show a general consistency with the orientation of the slab. The additional inversion for source duration allowed to verify the empirical correlation for moment normalized earthquakes in subduction zones among a decreasing rupture duration with increasing source depth, which was so far only observed for larger events.
The adaptation of cell growth and proliferation to environmental changes is essential for the surviving of biological systems. The evolutionary conserved Ser/Thr protein kinase “Target of Rapamycin” (TOR) has emerged as a major signaling node that integrates the sensing of numerous growth signals to the coordinated regulation of cellular metabolism and growth. Although the TOR signaling pathway has been widely studied in heterotrophic organisms, the research on TOR in photosynthetic eukaryotes has been hampered by the reported land plant resistance to rapamycin. Thus, the finding that Chlamydomonas reinhardtii is sensitive to rapamycin, establish this unicellular green alga as a useful model system to investigate TOR signaling in photosynthetic eukaryotes.
The observation that rapamycin does not fully arrest Chlamydomonas growth, which is different from observations made in other organisms, prompted us to investigate the regulatory function of TOR in Chlamydomonas in context of the cell cycle. Therefore, a growth system that allowed synchronously growth under widely unperturbed cultivation in a fermenter system was set up and the synchronized cells were characterized in detail. In a highly resolved kinetic study, the synchronized cells were analyzed for their changes in cytological parameters as cell number and size distribution and their starch content. Furthermore, we applied mass spectrometric analysis for profiling of primary and lipid metabolism. This system was then used to analyze the response dynamics of the Chlamydomonas metabolome and lipidome to TOR-inhibition by rapamycin
The results show that TOR inhibition reduces cell growth, delays cell division and daughter cell release and results in a 50% reduced cell number at the end of the cell cycle. Consistent with the growth phenotype we observed strong changes in carbon and nitrogen partitioning in the direction of rapid conversion into carbon and nitrogen storage through an accumulation of starch, triacylglycerol and arginine. Interestingly, it seems that the conversion of carbon into triacylglycerol occurred faster than into starch after TOR inhibition, which may indicate a more dominant role of TOR in the regulation of TAG biosynthesis than in the regulation of starch.
This study clearly shows, for the first time, a complex picture of metabolic and lipidomic dynamically changes during the cell cycle of Chlamydomonas reinhardtii and furthermore reveals a complex regulation and adjustment of metabolite pools and lipid composition in response to TOR inhibition.
What is a radical? Somebody who goes against mainstream opinions? An agitator who suggests transforming society at the risk of endangering its harmony? In the political context of the British Isles at the end of the eighteenth century, the word radical had a negative connotation. It referred to the Levellers and the English Civil War, it brought back a period of history which was felt as a traumatic experience. Its stigmas were still vivid in the mind of the political leaders of these times. The reign of Cromwell was certainly the main reason for the general aversion of any form of virulent contestation of the power, especially when it contained political claims.
In the English political context, radicalism can be understood as the different campaigns for parliamentary reforms establishing universal suffrage. However, it became evident that not all those who were supporting such a reform originated from the same social class or shared the same ideals. As a matter of fact, the reformist associations and their leaders often disagreed with each other. Edward Royle and Hames Walvin claimed that radicalism could not be analyzed historically as a concept, because it was not a homogeneous movement, nor it had common leaders and a clear ideology. For them, radicalism was merely a loose concept, « a state of mind rather than a plan of action. »
At the beginning of the nineteenth-century, the newspaper The Northern Star used the word radical in a positive way to designate a person or a group of people whose ideas were conform to those of the newspaper. However, an opponent of parliamentary reform will use the same word in a negative way, in this case the word radical will convey a notion of menace. From the very beginning, the term radical covered a large spectrum of ideas and conceptions. In fact, the plurality of what the word conveys is the main characteristic of what a radical is. As a consequence, because the radicals tended to differentiate themselves with their plurality and their differences rather than with common features, it seems impossible to define what radicalism (whose suffix in –ism implies that it designate a doctrine, an ideology) is. Nevertheless, today it is accepted by all historians. From the mid-twentieth century, we could say that it was taken from granted to consider radicalism as a movement that fitted with the democratic precepts (universal suffrage, freedom of speech) of our modern world.
Let us first look at radicalism as a convenient way to designate the different popular movements appealing to universal suffrage during the time period 1792-1848. We could easily observe through the successions of men and associations, a long lasting radical state of mind: Cartwright, Horne Tooke, Thomas Hardy, Francis Burdett, William Cobbett, Henry Hunt, William Lovett, Bronterre O’Brien, Feargus O’Connor, The London Society for Constitutional information (SCI), The London Corresponding Society (LCS), The Hampden Clubs, The Chartists, etc. These organizations and people acknowledged having many things in common and being inspired by one another in carrying out their activities. These influences can be seen in the language and the political ideology that British historians name as "Constitutionalist", but also, in the political organization of extra-parliamentary societies. Most of the radicals were eager to redress injustices and, in practice, they were inspired by a plan of actions drawn on from the pamphlets of the True Whigs of the eighteenth-century. We contest the argument that the radicals lacked coherence and imagination or that they did not know how to put into practice their ambitions. In fact, their innovative forms of protest left a mark on history and found many successors in the twentieth century. Radicals’ prevarications were the result of prohibitive legislation that regulated the life of associations and the refusal of the authorities to cooperate with them.
As mentioned above, the term radical was greatly used and the contemporaries of the period starting from the French Revolution to Chartism never had to quarrel about the notions the word radical covered. However, this does not imply that all radicals were the same or that they belong to the same entity. Equally to Horne Tooke, the Reverend and ultra-Tory Stephens was considered as a radical, it went also with the shoemaker Thomas Hardy and the extravagant aristocrat Francis Burdett. Whether one belonged to the Aristocracy, the middle-class, the lower class or the Church, nothing could prevent him from being a radical. Surely, anybody could be a radical in its own way. Radicalism was wide enough to embrace everybody, from revolutionary reformers to paternalistic Tories.
We were interested to clarify the meaning of the term radical because its inclusive nature was overlooked by historians. That’s why the term radical figures in the original title of our dissertation Les voix/voies radicales (radical voices/ways to radicalism). In the French title, both words voix/voies are homonymous; the first one voix (voice) correspond to people, the second one voies (ways) refers to ideas. By this, we wanted to show that the word radical belongs to the sphere of ideas and common experience but also to the nature of human beings.
Methodoloy
The thesis stresses less on the question of class and its formation than on the circumstances that brought people to change their destiny and those of their fellows or to modernize the whole society. We challenged the work of E.P. Thompson, who in his famous book, The Making of the English Working Class, defined the radical movements in accordance with an idea of class.
How a simple shoe-maker, Thomas Hardy, could become the center of attention during a trial where he was accused of being the mastermind of a modern revolution? What brought William Cobbett, an ultra-Tory, self-taught intellectual, to gradually espouse the cause of universal suffrage at a period where it was unpopular to do so? Why a whole population gathered to hear Henry Hunt, a gentleman farmer whose background did not destine him for becoming the champion of the people? It seemed that the easiest way to answer to these questions and to understand the nature of the popular movements consisted in studying the life of their leaders. We aimed at reconstructing the universe which surrounded the principal actors of the reform movements as if we were a privileged witness of theses times.
This idea to associate the biographies of historical characters for a period of more than fifty years arouse when we realized that key events of the reform movements were echoing each other, such the trial of Thomas Hardy in 1794 and the massacre of Peterloo of 1819. The more we learned about the major events of radicalism and the life of their leaders, the more we were intrigued. Finally, one could ask himself if being a radical was not after all a question of character rather than one of class. The different popular movements in favour of a parliamentary reform were in fact far more inclusive and diversified from what historians traditionally let us to believe. For instance, once he manage to gather a sufficient number of members of the popular classes, Thomas Hardy projected to give the control of his association to an intellectual elite led by Horne Tooke.
Moreover, supporters of the radical reforms followed leaders whose background was completely different as theirs. For example, O’Connor claimed royal descent from the ancient kings of Ireland. William Cobbett, owner of a popular newspaper was proud of his origins as a farmer. William Lovett, close to the liberals and a few members of parliament came from a very poor family of fishermen. We have thus put together the life of these five men, Thomas hardy, William Cobbett, Henry Hunt, William Lovett and Feargus O’Connor in order to compose a sort of a saga of the radicals. This association gives us a better idea of the characteristics of the different movements in which they participated, but also, throw light on the circumstances of their formation and their failures, on the particular atmosphere which prevailed at these times, on the men who influenced these epochs, and finally on the marks they had left. These men were at the heart of a whole network and in contact with other actors of peripheral movements. They gathered around themselves close and loyal fellows with whom they shared many struggles but also quarreled and had strong words.
The original part of our approach is reflected in the choice to not consider studying the fluctuations of the radical movements in a linear fashion where the story follows a strict chronology. We decided to split up the main issue of the thesis through different topics. To do so, we simply have described the life of the people who inspired these movements. Each historical figure covers a chapter, and the general story follows a chronological progression. Sometimes we had to go back through time or discuss the same events in different chapters when the main protagonists lived in the same period of time.
Radical movements were influenced by people of different backgrounds. What united them above all was their wish to obtain a normalization of the political world, to redress injustices and obtain parliamentary reform. We paid particular attention to the moments where the life of these men corresponded to an intense activity of the radical movement or to a transition of its ideas and organization. We were not so much interested in their feelings about secondary topics nor did we about their affective relations. Furthermore, we had little interest in their opinions on things which were not connected to our topic unless it helped us to have a better understanding of their personality. We have purposely reduced the description of our protagonists to their radical sphere. Of course we talked about their background and their intellectual development; people are prone to experience reversals of opinions, the case of Cobbett is the most striking one.
The life of these personalities coincided with particular moments of the radical movement, such as the first popular political associations, the first open-air mass meetings, the first popular newspapers, etc. We wanted to emphasize the personalities of those who addressed speeches and who were present in the radical associations. One could argue that the inconvenience of focusing on a particular person presents a high risk of overlooking events and people who were not part of his world. However, it was essential to differ from an analysis or a chronicle which had prevailed in the studies of the radical movements, as we aimed at offering a point of view that completed the precedents works written on that topic. In order to do so, we have deliberately put the humane character of the radical movement at the center of our work and used the techniques of biography as a narrative thread.
Conclusion
The life of each historical figure that we have portrayed corresponded to a particular epoch of the radical movement. Comparing the speeches of the radical leaders over a long period of time, we noticed that the radical ideology evolved. The principles of the Rights of Men faded away and gave place to more concrete reasoning, such as the right to benefit from one’s own labour. This transition is characterized by the Chartist period of Feargus O’Connor. This does not mean that collective memory and radical tradition ceased to play an important part. The popular classes were always appealed to Constitutional rhetoric and popular myths. Indeed, thanks to them they identified themselves and justified their claims to universal suffrage.
We focused on the life of a few influent leaders of radicalism in order to understand its evolution and its nature. The description of their lives constituted our narrative thread and it enabled us to maintain consistency in our thesis. If the chapters are independent the one from the other, events and speeches are in correspondences. Sometimes we could believe that we were witnessing a repetition of facts and events as if history was repeating itself endlessly. However, like technical progress, the spirit of time, Zeitgeist, experiences changes and mutations. These features are fundamental elements to comprehend historical phenomena; the latter cannot be simplified to philosophical, sociological, or historical concept. History is a science which has this particularity that the physical reality of phenomena has a human dimension. As a consequence, it is essential not to lose touch with the human aspect of history when one pursues studies and intellectual activities on a historical phenomenon.
We decided to take a route opposite to the one taken by many historians. We have first identified influential people from different epochs before entering into concepts analysis. Thanks to this compilation of radical leaders, a new and fresh look to the understanding of radicalism was possible. Of course, we were not the first one to have studied them, but we ordered them following a chronology, like Plutarch enjoyed juxtaposing Greeks and Romans historical figures. Thanks to this technique we wanted to highlight the features of the radical leaders’ speeches, personalities and epochs, but also their differences. At last, we tried to draw the outlines and the heart of different radical movements in order to follow the ways that led to radicalism. We do not pretend to have offered an original and exclusive definition of radicalism, we mainly wanted to understand the nature of what defines somebody as a radical and explain the reasons why thousands of people decided to believe in this man. Moreover, we wanted to distance ourselves from the ideological debate of the Cold War which permeated also the interpretation of past events. Too often, the history of radicalism was either narrated with a form of revolutionary nostalgia or in order to praise the merits of liberalism.
If the great mass meetings ends in the mid-nineteenth-century with the fall of Chartism, this practice spread out in the whole world in the twentieth-century. Incidentally, the Arab Spring of the beginning of the twenty-first-century demonstrated that a popular platform was the best way for the people to claim their rights and destabilize a political system which they found too authoritative. Through protest the people express an essential quality of revolt, which is an expression of emancipation from fear. From then on, a despotic regime loses this psychological terror which helped it to maintain itself into power. The balance of power between the government and its people would also take a new turn. The radicals won this psychological victory more than 150 years ago and yet universal suffrage was obtained only a century later. From the acceptance of the principles of liberties to their cultural practice, a long route has to be taken to change people’s mind. It is a wearisome struggle for the most vulnerable people. In the light of western history, fundamental liberties must be constantly defended. Paradoxically, revolt is an essential and constitutive element of the maintenance of democracy.
Die vorliegende Studie beschäftigte sich mit der Bedeutung der dysfunktionalen Einstellungen für die Entwicklung von depressiven Symptomen bei Kindern und Jugendlichen. Nach der kognitiven Theorie der Depression von Beck (1967, 1996) führen dysfunktionale Einstellungen in Interaktion mit Stress zu depressiven Symptomen. Es existieren allerdings nur wenige Studien, die die longitudinale Beziehung zwischen den dysfunktionalen Einstellungen und der Depressivität bei Kindern und Jugendlichen untersucht haben (Lakdawalla et al., 2007). Folglich kann noch nicht eindeutig geklärt werden, ob die dysfunktionalen Einstellungen Ursache, Begleiterscheinung oder Konsequenz der Depression sind. Als Datengrundlage diente eine Stichprobe von Kindern und Jugendlichen im Alter von 9 bis 20 Jahren, die im Rahmen der PIER-Studie zu dysfunktionalen Einstellungen, kritischen Lebensereignissen und depressiven Symptomen befragt wurden (Nt1t2 = 1.053; t1: 2011/2012, t2: 2013/2014). Querschnittliche Analysen zeigten hohe Assoziationen zwischen den dysfunktionalen Einstellungen, kritischen Lebensereignissen und depressiven Symptomen. Eine latente Moderationsanalyse wies nur bei den Jugendlichen auf signifikante Interaktion zwischen den dysfunktionalen Einstellungen und den kritischen Lebensereignissen in der Vorhersage depressiver Symptomatik hin. Im Längsschnitt zeigten latente Cross-Lagged-Panel-Analysen erwartungsgemäß, dass die dysfunktionalen Einstellungen und die Depressivität mit dem Alter immer stabilere Konstrukte darstellen, die sehr eng miteinander zusammenhängen. Eine diesem Modell hinzugefügte latente Moderationsanalyse konnte das kognitive Modell der Depression nach Beck weder bei Kindern noch bei Jugendlichen bestätigen. Die spätere depressive Symptomatik konnte lediglich durch Haupteffekte der früheren Ausprägung der Depressivität und der kritischen Lebensereignisse vorhergesagt werden. Diese Ergebnisse legen den Schluss nahe, dass es sich bei den dysfunktionalen Einstellungen eher um Begleiterscheinungen als um Risikofaktoren oder Konsequenzen der depressiven Symptomatik handelt.
Con la sua proposta di una Somaestetica, articolata fondamentalmente in analitica, pragmatica e pratica, Richard Shusterman intende in primo luogo fornire e creare una cornice metodologica, un orientamento unitario che sia in grado di rintracciare, ricostruire e portare a manifestazione - all’interno di eterogenee riflessioni teoriche e pratiche somatiche - la comune esigenza di ridare luce alla dimensione corporea come modo primario di essere nel mondo. Recuperando l’accezione baumgarteniana di Aesthetica come gnoseologia inferiore, arte dell’analogo della ragione, scienza della conoscenza sensibile, la somaestetica intende dare nuovo impulso alla più profonda radice di estetica e filosofia che coglie la vita nel suo processo di metamorfosi e rigenerazione continua, in quel respiro vitale che, per quanto possa diventare cosciente, non è mai totalmente afferrabile dalla ragione discorsiva, situandosi piuttosto in quello spazio primordiale in cui coscienza e corpo si coappartengono, in cui il soggetto non è ancora individualizzabile perché fuso con l’ambiente, non è totalmente privatizzabile perché intrinsecamente plasmato dal tessuto sociale cui egli stesso conferisce dinamicamente forma. A partire dunque dalla rivalutazione del concetto di Aisthesis la disciplina somaestetica mira ad una intensificazione di sensorialità, percezione, emozione, commozione, rintracciando proprio nel Soma la fonte di quelle facoltà “inferiori” irriducibili a quelle puramente intellettuali, che permettono di accedere alle dimensioni qualitative dell’esperienza, di portare a manifestazione e far maturare l’essere umano come essere indivisibile che non si lascia incontrare da un pensiero che ne rinnega l’unitarietà in nome di fittizie e laceranti distinzioni dicotomiche. Nel corpo infatti si radicano in modo silente regole, convenzioni, norme e valori socioculturali che determinano e talvolta limitano la configurazione ed espressione di sensazioni, percezioni, cognizioni, pensieri, azioni, volizioni, disposizioni di un soggetto da sempre inserito in una Mitwelt (mondo comune), ed è allora proprio al corpo che bisogna rivolgersi per riconfigurare più autentiche modalità di espressione del soggetto che crea equilibri dinamici per mantenere una relazione di coerenza con il più ampio contesto sociale, culturale, ambientale. L’apertura al confronto con eterogenee posizioni filosofiche e l’intrinseca multidisciplinarietà spiegano la centralità nel contemporaneo dibattito estetologico internazionale della Somaestetica che, rivolgendosi tanto ad una formulazione teorica quanto ad una concreta applicazione pratica, intende rivalutare il soma come corporeità intelligente, senziente, intenzionale e attiva, non riducibile all’accezione peccaminosa di caro (mero corpo fisico privo di vita e sensazione). Attraverso la riflessione e la pratica di tecniche di coscienza somatica si portano in primo piano i modi in cui il sempre più consapevole rapporto con la propria corporeità come mediatamente esperita e immediatamente vissuta, sentita, offre occasioni autentiche di realizzazione progressiva di sé innanzitutto come persone, capaci di autocoltivazione, di riflessione cosciente sulle proprie abitudini incorporate, di ristrutturazione creativa di sé, di intensificata percezione e apprezzamento sensoriale sia nel concreto agire quotidiano, sia nella dimensione più propriamente estetologica di ricezione, fruizione e creazione artistica. L’indirizzo essenzialmente pragmatista della riflessione di Shusterman traccia così una concezione fondamentalmente relazionale dell’estetica in grado di porsi proprio nel movimento e nel rapporto continuamente diveniente di vera e propria trasformazione e passaggio tra le dimensioni fisiche, proprio-corporee, psichiche e spirituali del soggetto la cui interazione, ed il cui reciproco riversarsi le une nelle altre, può risultare profondamente arricchito attraverso una progressiva e sempre crescente consapevolizzazione della ricchezza della dimensione corporea in quanto intenzionale, percettiva, senziente, volitiva, tanto quanto vulnerabile, limitante, caduca, patica. Il presente lavoro intende ripercorrere ed approfondire alcuni dei principali referenti di Shusterman, focalizzandosi prevalentemente sulla radice pragmatista della sua proposta e sul confronto con il dibattito di area tedesca tra estetica, antropologia filosofica, neofenomenologia e antropologia medica, per riguadagnare una nozione di soma che proprio a partire dal contrasto, dall’impatto irriducibile con la potenza annullante delle situazioni limite, della crisi possa acquisire un più complesso e ricco valore armonizzante delle intrinseche e molteplici dimensioni che costituiscono il tessuto della soggettività incarnata. In particolare il primo capitolo (1. Somaestetica) chiarisce le radici essenzialmente pragmatiste della proposta shustermaniana e mostra come sia possibile destrutturare e dunque riconfigurare radicati modi di esperienza, rendendo coscienti abitudini e modi di vivere che si fissano a livello somatico in modo per lo più inavvertito. Il confronto con la nozione di Habitus, di cui Pierre Bourdieu mette brillantemente in luce l’invisibile e socialmente determinata matrice somatica, lascia scorgere come ogni manifestazione umana sia sostenuta dall’incorporazione di norme, credenze, valori che determinano e talvolta limitano l’espressione, lo sviluppo, persino le predisposizioni e le inclinazioni degli individui. Ed è proprio intervenendo a questo livello che si può restituire libertà alle scelte e aprirsi così alle dimensioni essenzialmente qualitative dell’esperienza che, nell’accezione deweyana è un insieme olistico unitario e coeso che fa da sfondo alle relazioni organismo-ambiente, un intreccio inestricabile di teoria e prassi, particolare e universale, psiche e soma, ragione ed emozione, percettivo e concettuale, insomma quell’immediata conoscenza corporea che struttura lo sfondo di manifestazione della coscienza.
Die Dissertation wird der rechtsstaatlichen Problematik in der Verfassung von Georgien und in der Rechtsprechung des Verfassungsgerichts Georgiens gewidmet und bietet eine umfangreiche Analyse der wichtigsten Rechtsstaatsmerkmale in dieser Hinsicht. Neben dieser Analyse der früheren und bestehenden Gegebenheiten, prognostiziert sie mittels der perspektivistischen Denkmodele zukünftige Entwicklungen und schlägt eventuelle Lösungswege von Problemen vor. Bei der Arbeit an der Dissertation wurde insbesondere die reiche Erfahrung der deutschen Rechtsstaatsdogmatik in Anspruch genommen.
Cyanobacteria produce about 40 percent of the world’s primary biomass, but also a variety of often toxic peptides such as microcystin. Mass developments, so called blooms, can pose a real threat to the drinking water supply in many parts of the world. This study aimed at characterizing the biological function of microcystin production in one of the most common bloom-forming cyanobacterium Microcystis aeruginosa.
In a first attempt, the effect of elevated light intensity on microcystin production and its binding to cellular proteins was studied. Therefore, conventional microcystin quantification techniques were combined with protein-biochemical methods. RubisCO, the key enzyme for primary carbon fixation was a major microcystin interaction partner. High light exposition strongly stimulated microcystin-protein interactions. Up to 60 percent of the total cellular microcystin was detected bound to proteins, i.e. inaccessible for standard quantification procedures. Underestimation of total microcystin contents when neglecting the protein fraction was also demonstrated in field samples. Finally, an immuno-fluorescence based method was developed to identify microcystin producing cyanobacteria in mixed populations.
The high light induced microcystin interaction with proteins suggested an impact of the secondary metabolite on the primary metabolism of Microcystis by e.g. modulating the activity of enzymes. For addressing that question, a comprehensive GC/MS-based approach was conducted to compare the accumulation of metabolites in the wild-type of Microcystis aeruginosa PCC 7806 and the microcystin deficient ΔmcyB mutant. From all 501 detected non-redundant metabolites 85 (17 percent) accumulated significantly different in either of both genotypes upon high light exposition. Accumulation of compatible solutes in the ΔmcyB mutant suggests a role of microcystin in fine-tuning the metabolic flow to prevent stress related to excess light, high oxygen concentration and carbon limitation.
Co-analysis of the widely used model cyanobacterium Synechocystis PCC 6803 revealed profound metabolic differences between species of cyanobacteria. Whereas Microcystis channeled more resources towards carbohydrate synthesis, Synechocystis invested more in amino acids. These findings were supported by electron microscopy of high light treated cells and the quantification of storage compounds. While Microcystis accumulated mainly glycogen to about 8.5 percent of its fresh weight within three hours, Synechocystis produced higher amounts of cyanophycin. The results showed that the characterization of species-specific metabolic features should gain more attention with regard to the biotechnological use of cyanobacteria.