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Arachidonsäurelipoxygenasen (ALOX-Isoformen) sind Lipid-peroxidierenden Enzyme, die bei der Zelldifferenzierung und bei der Pathogenese verschiedener Erkrankungen bedeutsam sind. Im menschlichen Genom gibt es sechs funktionelle ALOX-Gene, die als Einzelkopiegene vorliegen. Für jedes humane ALOX-Gen gibt es ein orthologes Mausgen. Obwohl sich die sechs humanen ALOX-Isoformen strukturell sehr ähnlich sind, unterscheiden sich ihre funktionellen Eigenschaften deutlich voneinander. In der vorliegenden Arbeit wurden vier unterschiedliche Fragestellungen zum Vorkommen, zur biologischen Rolle und zur Evolutionsabhängigkeit der enzymatischen Eigenschaften von Säugetier-ALOX-Isoformen untersucht:
1) Spitzhörnchen (Tupaiidae) sind evolutionär näher mit dem Menschen verwandt als Nagetiere und wurden deshalb als Alternativmodelle für die Untersuchung menschlicher Erkrankungen vorgeschlagen. In dieser Arbeit wurde erstmals der Arachidonsäurestoffwechsel von Spitzhörnchen untersucht. Dabei wurde festgestellt, dass im Genom von Tupaia belangeri vier unterschiedliche ALOX15-Gene vorkommen und die Enzyme sich hinsichtlich ihrer katalytischen Eigenschaften ähneln. Diese genomische Vielfalt, die weder beim Menschen noch bei Mäusen vorhanden ist, erschwert die funktionellen Untersuchungen zur biologischen Rolle des ALOX15-Weges. Damit scheint Tupaia belangeri kein geeigneteres Tiermodel für die Untersuchung des ALOX15-Weges des Menschen zu sein.
2) Entsprechend der Evolutionshypothese können Säugetier-ALOX15-Orthologe in Arachidonsäure-12-lipoxygenierende- und Arachidonsäure-15-lipoxygenierende Enzyme eingeteilt werden. Dabei exprimieren Säugetierspezies, die einen höheren Evolutionsgrad als Gibbons aufweisen, Arachidonsäure-15-lipoxygenierende ALOX15-Orthologe, während evolutionär weniger weit entwickelte Säugetiere Arachidonsäure-12 lipoxygenierende Enzyme besitzen. In dieser Arbeit wurden elf neue ALOX15-Orthologe als rekombinante Proteine exprimiert und funktionell charakterisiert. Die erhaltenen Ergebnisse fügen sich widerspruchsfrei in die Evolutionshypothese ein und verbreitern deren experimentelle Basis. Die experimentellen Daten bestätigen auch das Triadenkonzept.
3) Da humane und murine ALOX15B-Orthologe unterschiedliche funktionelle Eigenschaften aufweisen, können Ergebnisse aus murinen Krankheitsmodellen zur biologischen Rolle der ALOX15B nicht direkt auf den Menschen übertragen werden. Um die ALOX15B-Orthologen von Maus und Mensch funktionell einander anzugleichen, wurden im Rahmen der vorliegenden Arbeit Knock-in Mäuse durch die In vivo Mutagenese mittels CRISPR/Cas9-Technik hergestellt. Diese exprimieren eine humanisierte Mutante (Doppelmutation von Tyrosin603Asparaginsäure+Histidin604Valin) der murinen Alox15b. Diese Mäuse waren lebens- und fortpflanzungsfähig, zeigten aber geschlechtsspezifische Unterschiede zu ausgekreuzten Wildtyp-Kontrolltieren im Rahmen ihre Individualentwicklung.
4) In vorhergehenden Untersuchungen zur Rolle der ALOX15B in Rahmen der Entzündungsreaktion wurde eine antiinflammatorische Wirkung des Enzyms postuliert. In der vorliegenden Arbeit wurde untersucht, ob eine Humanisierung der murinen Alox15b die Entzündungsreaktion in zwei verschiedenen murinen Entzündungsmodellen beeinflusst. Eine Humanisierung der murinen Alox15b führte zu einer verstärkten Ausbildung von Entzündungssymptomen im induzierten Dextran-Natrium-Sulfat-Kolitismodell. Im Gegensatz dazu bewirkte die Humanisierung der Alox15b eine Abschwächung der Entzündungssymptome im Freund‘schen Adjuvans Pfotenödemmodell. Diese Daten deuten darauf hin, dass sich die Rolle der ALOX15B in verschiedenen Entzündungsmodellen unterscheidet.
Unternehmenssteuerrecht
(2024)
Das Unternehmenssteuerrecht gilt als schwierige Spezialmaterie. Wer in diesem praktisch wichtigen Rechtsgebiet den Durchblick behalten will, muss die relevanten Zusammenhänge verstehen. Der stringente Aufbau und zahlreiche – zumeist an die BFH-Rechtsprechung angelehnte – Beispiele des „Hüttemann/Schön" erleichtern ebenso wie viele Querverweise den Überblick und die Durchdringung der Zusammenhänge.
Das Werk eröffnet nicht nur interessierten Studierenden der Rechtswissenschaften, Wirtschaftswissenschaften und Steuerwissenschaften einen systematischen Zugang zum Unternehmenssteuerrecht. Er richtet sich auch an Praktiker, die bei ihrer beratenden und gestaltenden Tätigkeit auf hinreichende Kenntnisse und ein vertieftes Verständnis dieses Rechtsgebiets angewiesen sind.
The contribution explores how an understanding of neoliberal subjectification in socio-economic education can serve to counteract the trend marketisation of democracy. Drawing on Foucault’s lectures on biopolitics and Brown’s current analysis of neoliberalism, it lays out a sociological explanation that treats the idea of homo economicus as a structuring element of our society and outlines the threat this poses to the liberal democratic order. The second part of the contribution outlines – through immanent critique – an ideology-critical analytical competence that uses key problems to illuminate socially critical perspectives on social reality. The objective is to challenge some of the foundations of social order (Salomon, D. Kritische politische Bildung. Ein Versuch. In B. Widmaier & Overwien, B. (Hrsg.), Was heißt heute kritische politische Bildung? (S. 232–239). Wochenschau, 2013) in pursuit of the ultimate objective of an educated and assertive citizenry.
Der tänzerische Kreativitätstest stellt ein valides Instrumentarium dar, welches auf tanzspezifischen Aufgaben basiert und für die differenzierte und standardisierte Erfassung der tänzerischen Kreativität bei Kindern im Alter von 8 bis 12 Jahren konzipiert ist. Mit dem tänzerischen Kreativitätstest können nicht nur Fragestellungen zum Stand sowie zur Entwicklung tänzerisch-kreativer Fähigkeiten im Kindesalter bearbeitet werden, sondern er liefert auch wertvolle Informationen für die Optimierung von Trainings-, Förder- und Vermittlungsmaßnahmen. Erfasst werden folgende tänzerisch-kreativen Fähigkeiten: 1) Vielfalt und Originalität in der Fortbewegung und in Körperpositionen sowie 2) Ideenreichtum, Vielfalt und Originalität in der Gestaltung von Bewegungspatterns und -kompositionen. Dieser Test lässt sich mit größeren Gruppen und minimalem materiellen Aufwand durchführen, ist zeitlich unbeschränkt und ermöglicht es, unterschiedliche Leistungsniveaus zu identifizieren. Der tänzerische Kreativitätstest bietet Forschenden und Lehrkräften eine wertvolle Möglichkeit, die tänzerisch-kreativen Fähigkeiten von Kindern zu analysieren und zu fördern.
Der Band ist den existenziellen Turbulenzen gewidmet, die dem Menschen nicht als katastrophales Ereignis widerfahren, sondern seinen unentrinnbaren Alltag formen. Egal ob Verschiebungen im universitären Selbstverständnis (Vinken), Umgang mit geschlechtlicher Abweichung (Ungelenk; Hordych), Brüchen im Familiengefüge (Brook; Goldmann), Kampf gegen Abholzung (Nixon), technische Totalüberwachung im Alltag (Søilen/Maurer), narratologische Erkundungen von Zeit oder Gattung (Horst; Pierstorff; Reisener), stets erweist sich scheinbar banaler Alltag als erstaunlich produktiver Ausgangspunkt für gesellschaftliche, künstlerische und denkerische Prozesse. Das Gewöhnliche des Alltags ist nicht länger bloß statische Folie für einbrechende Ereignisse – es ist selbst als generatives Werden nobilitiert, das nun aber doppelbödige Wertung annimmt: Alltag verliert im Zuge einer Philosophie der Moderne das Verlässliche (Hüsch; Khurana), wird bedrohlich; zugleich bietet diese neue Unruhe des Alltags, sein "trouble", aber auch Chancen für Veränderung und feministisch-kritische oder künstlerische Intervention.
Open edX is an incredible platform to deliver MOOCs and SPOCs, designed to be robust and support hundreds of thousands of students at the same time. Nevertheless, it lacks a lot of the fine-grained functionality needed to handle students individually in an on-campus course. This short session will present the ongoing project undertaken by the 6 public universities of the Region of Madrid plus the Universitat Politècnica de València, in the framework of a national initiative called UniDigital, funded by the Ministry of Universities of Spain within the Plan de Recuperación, Transformación y Resiliencia of the European Union. This project, led by three of these Spanish universities (UC3M, UPV, UAM), is investing more than half a million euros with the purpose of bringing the Open edX platform closer to the functionalities required for an LMS to support on-campus teaching. The aim of the project is to coordinate what is going to be developed with the Open edX development community, so these developments are incorporated into the core of the Open edX platform in its next releases. Features like a complete redesign of platform analytics to make them real-time, the creation of dashboards based on these analytics, the integration of a system for customized automatic feedback, improvement of exams and tasks and the extension of grading capabilities, improvements in the graphical interfaces for both students and teachers, the extension of the emailing capabilities, redesign of the file management system, integration of H5P content, the integration of a tool to create mind maps, the creation of a system to detect students at risk, or the integration of an advanced voice assistant and a gamification mobile app, among others, are part of the functionalities to be developed. The idea is to transform a first-class MOOC platform into the next on-campus LMS.
Assessing the impact of global change on hydrological systems is one of the greatest hydrological challenges of our time. Changes in land cover, land use, and climate have an impact on water quantity, quality, and temporal availability. There is a widespread consensus that, given the far-reaching effects of global change, hydrological systems can no longer be viewed as static in their structure; instead, they must be regarded as entire ecosystems, wherein hydrological processes interact and coevolve with biological, geomorphological, and pedological processes. To accurately predict the hydrological response under the impact of global change, it is essential to understand this complex coevolution. The knowledge of how hydrological processes, in particular the formation of subsurface (preferential) flow paths, evolve within this coevolution and how they feed back to the other processes is still very limited due to a lack of observational data.
At the hillslope scale, this intertwined system of interactions is known as the hillslope feedback cycle. This thesis aims to enhance our understanding of the hillslope feedback cycle by studying the coevolution of hillslope structure and hillslope hydrological response. Using chronosequences of moraines in two glacial forefields developed from siliceous and calcareous glacial till, the four studies shed light on the complex coevolution of hydrological, biological, and structural hillslope properties, as well as subsurface hydrological flow paths over an evolutionary period of 10 millennia in these two contrasting geologies. The findings indicate that the contrasting properties of siliceous and calcareous parent materials lead
to variations in soil structure, permeability, and water storage. As a result, different plant species and vegetation types are favored on siliceous versus calcareous parent material, leading to diverse ecosystems with distinct hydrological dynamics. The siliceous parent material was found to show a higher activity level in driving the coevolution. The soil pH resulting from parent material weathering emerges as a crucial factor, influencing vegetation development, soil formation, and consequently, hydrology. The acidic weathering of the siliceous parent material favored the accumulation of organic matter, increasing the soils’ water storage capacity and attracting acid-loving shrubs, which further promoted organic matter accumulation and ultimately led to podsolization after 10 000 years. Tracer experiments revealed that the subsurface flow path evolution was influenced by soil and vegetation development, and vice versa. Subsurface flow paths changed from vertical, heterogeneous matrix flow to finger-like flow paths over a few hundred years, evolving into macropore flow, water storage, and lateral subsurface flow after several thousand years. The changes in flow paths among younger age classes were driven by weathering processes altering soil structure, as well as by vegetation development and root activity. In the older age
class, the transition to more water storage and lateral flow was attributed to substantial organic matter accumulation and ongoing podsolization. The rapid vertical water transport in the finger-like flow paths, along with the conductive sandy material, contributed to podsolization and thus to the shift in the hillslope hydrological response.
In contrast, the calcareous site possesses a high pH buffering capacity, creating a neutral to basic environment with relatively low accumulation of dead organic matter, resulting in a lower water storage capacity and the establishment of predominantly grass vegetation. The coevolution was found to be less dynamic over the millennia. Similar to the siliceous site, significant changes in subsurface flow paths occurred between the young age classes. However, unlike the siliceous site, the subsurface flow paths at the calcareous site only altered in shape and not in direction. Tracer experiments showed that flow paths changed from vertical, heterogeneous matrix flow to vertical, finger-like flow paths after a few hundred to thousands of years, which was driven by root activities and weathering processes. Despite having a finer soil texture, water storage at the calcareous site was significantly lower than at the siliceous site, and water transport remained primarily rapid and vertical, contributing to the flourishing of grass vegetation.
The studies elucidated that changes in flow paths are predominantly shaped by the characteristics of the parent material and its weathering products, along with their complex interactions with initial water flow paths and vegetation development. Time, on the other hand, was not found to be a primary factor in describing the evolution of the hydrological response. This thesis makes a valuable contribution to closing the gap in the observations of the coevolution of hydrological processes within the hillslope feedback cycle, which is important to improve predictions of hydrological processes in changing landscapes. Furthermore, it emphasizes the importance of interdisciplinary studies in addressing the hydrological challenges arising from global change.
It is a well-attested finding in head-initial languages that individuals with aphasia (IWA) have greater difficulties in comprehending object-extracted relative clauses (ORCs) as compared to subject-extracted relative clauses (SRCs). Adopting the linguistically based approach of Relativized Minimality (RM; Rizzi, 1990, 2004), the subject-object asymmetry is attributed to the occurrence of a Minimality effect in ORCs due to reduced processing capacities in IWA (Garraffa & Grillo, 2008; Grillo, 2008, 2009). For ORCs, it is claimed that the embedded subject intervenes in the syntactic dependency between the moved object and its trace, resulting in greater processing demands. In contrast, no such intervener is present in SRCs. Based on the theoretical framework of RM and findings from language acquisition (Belletti et al., 2012; Friedmann et al., 2009), it is assumed that Minimality effects are alleviated when the moved object and the intervening subject differ in terms of relevant syntactic features. For German, the language under investigation, the RM approach predicts that number (i.e., singular vs. plural) and the lexical restriction [+NP] feature (i.e., lexically restricted determiner phrases vs. lexically unrestricted pronouns) are considered relevant in the computation of Minimality. Greater degrees of featural distinctiveness are predicted to result in more facilitated processing of ORCs, because IWA can more easily distinguish between the moved object and the intervener.
This cumulative dissertation aims to provide empirical evidence on the validity of the RM approach in accounting for comprehension patterns during relative clause (RC) processing in German-speaking IWA. For that purpose, I conducted two studies including visual-world eye-tracking experiments embedded within an auditory referent-identification task to study the offline and online processing of German RCs. More specifically, target sentences were created to evaluate (a) whether IWA demonstrate a subject-object asymmetry, (b) whether dissimilarity in the number and/or the [+NP] features facilitates ORC processing, and (c) whether sentence processing in IWA benefits from greater degrees of featural distinctiveness. Furthermore, by comparing RCs disambiguated through case marking (at the relative pronoun or the following noun phrase) and number marking (inflection of the sentence-final verb), it was possible to consider the role of the relative position of the disambiguation point. The RM approach predicts that dissimilarity in case should not affect the occurrence of Minimality effects. However, the case cue to sentence interpretation appears earlier within RCs than the number cue, which may result in lower processing costs in case-disambiguated RCs compared to number-disambiguated RCs.
In study I, target sentences varied with respect to word order (SRC vs. ORC) and dissimilarity in the [+NP] feature (lexically restricted determiner phrase vs. pronouns as embedded element). Moreover, by comparing the impact of these manipulations in case- and number-disambiguated RCs, the effect of dissimilarity in the number feature was explored. IWA demonstrated a subject-object asymmetry, indicating the occurrence of a Minimality effect in ORCs. However, dissimilarity neither in the number feature nor in the [+NP] feature alone facilitated ORC processing. Instead, only ORCs involving distinct specifications of both the number and the [+NP] features were well comprehended by IWA. In study II, only temporarily ambiguous ORCs disambiguated through case or number marking were investigated, while controlling for varying points of disambiguation. There was a slight processing advantage of case marking as cue to sentence interpretation as compared to number marking.
Taken together, these findings suggest that the RM approach can only partially capture empirical data from German IWA. In processing complex syntactic structures, IWA are susceptible to the occurrence of the intervening subject in ORCs. The new findings reported in the thesis show that structural dissimilarity can modulate sentence comprehension in aphasia. Interestingly, IWA can override Minimality effects in ORCs and derive correct sentence meaning if the featural specifications of the constituents are maximally different, because they can more easily distinguish the moved object and the intervening subject given their reduced processing capacities. This dissertation presents new scientific knowledge that highlights how the syntactic theory of RM helps to uncover selective effects of morpho-syntactic features on sentence comprehension in aphasia, emphasizing the close link between assumptions from theoretical syntax and empirical research.
It is a common finding that preschoolers have difficulties in identifying who is doing what to whom in non-canonical sentences, such as (object-verb-subject) OVS and passive sentences in German. This dissertation investigates how German monolingual and German-Italian simultaneous bilingual children process German OVS sentences in Study 1 and German passives in Study 2. Offline data (i.e., accuracy data) and online data (i.e., eye-gaze and pupillometry data) were analyzed to explore whether children can assign thematic roles during sentence comprehension and processing. Executive functions, language-internal and -external factors were investigated as potential predictors for children’s sentence comprehension and processing.
Throughout the literature, there are contradicting findings on the relation between language and executive functions. While some results show a bilingual cognitive advantage over monolingual speakers, others suggest there is no relationship between bilingualism and executive functions. If bilingual children possess more advanced executive function abilities than monolingual children, then this might also be reflected in a better performance on linguistic tasks. In the current studies monolingual and bilingual children were tested by means of two executive function tasks: the Flanker task and the task-switching paradigm. However, these findings showed no bilingual cognitive advantages and no better performance by bilingual children in the linguistic tasks. The performance was rather comparable between bilingual and monolingual children, or even better for the monolingual group. This may be due to cross-linguistic influences and language experience (i.e., language input and output). Italian was used because it does not syntactically overlap with the structure of German OVS sentences, and it only overlapped with one of the two types of sentence condition used for the passive study - considering the subject-(finite)verb alignment. The findings showed a better performance of bilingual children in the passive sentence structure that syntactically overlapped in the two languages, providing evidence for cross-linguistic influences.
Further factors for children’s sentence comprehension were considered. The parents’ education, the number of older siblings and language experience variables were derived from a language background questionnaire completed by parents. Scores of receptive vocabulary and grammar, visual and short-term memory and reasoning ability were measured by means of standardized tests. It was shown that higher German language experience by bilinguals correlates with better accuracy in German OVS sentences but not in passive sentences. Memory capacity had a positive effect on the comprehension of OVS and passive sentences in the bilingual group. Additionally, a role was played by executive function abilities in the comprehension of OVS sentences and not of passive sentences. It is suggested that executive function abilities might help children in the sentence comprehension task when the linguistic structures are not yet fully mastered.
Altogether, these findings show that bilinguals’ poorer performance in the comprehension and processing of German OVS is mainly due to reduced language experience in German, and that the different performance of bilingual children with the two types of passives is mainly due to cross-linguistic influences.