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Development of grammatical and lexical skills in argumentative EFL writing at upper secondary level in Germany and Switzerland
Get PDFThe ability to write argumentative essays is an important requirement in EFL curricula in Germany and Switzerland, with grammar and lexis serving as indispensable elements of this task. The literature shows that acquiring advanced grammatical and lexical skills is challenging for students, especially genre-specific lexical abilities. In this longitudinal study, we investigate how grammatical and lexical skills develop in two educational systems among learners at upper secondary schools (operationalized as number of grammatical and lexical errors). Based on texts from n = 470 learners at two time points at the beginning and end of Year 11, it shows that learners in both countries made more lexical than grammatical errors (partial η2 = .17). There were no differences between the countries. Longitudinal analyses revealed moderate positive developments in both grammatical and lexical skills over the course of one school year (partial η2 = .08). The study confirms the importance of vocabulary for advanced L2 writers, which seems to pose a larger challenge than grammar and warrants special attention in EFL writing at upper secondary school. Implications for teacher education and classroom practice such as the emulation of model texts are discussed, with a focus on lexical chunks typical of argumentative writing
scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome
Get PDFPost-COVID syndrome (PCS) affects approximately 3-17% of individuals following acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poses a potential global health burden. While improved assessment strategies are emerging, mechanistic insights and treatment options remain limited. This study investigates molecular mechanisms underlying PCS using single-cell RNA (scRNA) transcriptomics combined with in vitro validation. scRNA analysis is performed on nasal biopsies from 25 patients with moderate or severe PCS to investigate differential cell types, signalling pathways, and cell-cell communication. Air-liquid interface cultures are used to validate findings, focusing on the TNFα-TGFβ axis. Severe PCS shows reduced numbers of ciliated cells, increased immune cell infiltration, and heightened inflammatory signaling that drives TGFβ and TNFα upregulation, in the absence of a detectable viral load. These changes trigger epithelial-mesenchymal transition, basal cell expansion and a mis-stratified nasal epithelium. In vitro experiments confirm TGFβ and TNFα as causal cytokines promoting ciliated cell loss and increased basal cell abundance. These findings indicate a sustained severe PCS is not driven by ongoing viral load but by immune cell activity and chronic cytokine production. Targeting the TNFα-TGFβ axis may mitigate immune-mediated nasal tissue damage and support epithelium restoration, offering a potential therapeutic strategy for PCS
Clicking [Mo(CO)3(triphos)] to an azide-terminated alkylthiol SAM: structural, spectroscopic and electrochemical investigations
Get PDFThe synthesis and characterization of a new, linear triphos-type pincer ligand furnished with an ethynyl moiety in the ligand backbone (etPPPhTMSP) and the derived tricarbonyl complex [Mo(CO)3(etPPPhTMSP)] are described. Deprotection of the latter leads to [Mo(CO)3(etPPPhHP)] which in turn is clicked onto an N3-terminated Au-surface. The resulting monolayer is characterized by XPS, IRRAS and cyclic voltammetry, providing information on its chemical composition, the degree of surface coverage and the orientation of the headgroup. On the basis of these results, a protocol for the functionalization of surfaces with redox-active transition metal complexes for applications in, e.g., electrocatalysis is developed
Grassland restoration practice in Central Europe: drivers of success across a broad moisture gradient
Get PDFOngoing ecosystem degradation and loss demand restoration efforts worldwide. In Central Europe, semi-natural grasslands are in focus, and better understanding of restoration success and its drivers is needed. For practical projects, systematic screening remains lacking. We compared plant species composition of 41 recipient sites 3–18 years after restoration via plant material transfer with composition of their donor sites. Further, we analyzed establishment of habitat-typical and endangered species. Spanning a gradient of moisture conditions, sites were located in Germany and Luxembourg. Soil characteristics, biomass productivity, and restoration setup (e.g. previous site state, age) were investigated as potential drivers of success. In dry grasslands, success was highest, likely due to the creation of raw soils at several sites before plant material application. While raw soils generally favored the establishment of endangered species, the resulting low-productive and dry conditions sometimes posed challenges for mesic grassland restoration. In mesic grasslands, elevated soil pH of some recipient sites further contributed to divergence in species composition compared to donor sites. In alluvial grasslands, high nutrient and productivity levels of recipient sites impeded restoration success. Wet grasslands were successfully restored when soil moisture was sufficient. Across grassland types, species richness decreased with time since restoration, yet the number and cover of habitat-typical and endangered species remained stable. Introducing typical species in addition to plant material transfer supported restoration. We advocate for large-scale, systematic investigations of practical grassland restoration projects combined with well-defined monitoring guidelines across different regions to address this complex challenge in the coming decades
SAT-based String Solving: Solving String Constraints by Reduction to Boolean Satisfiability
Get PDFString constraint solving is the task of checking whether first-order formulas over strings are satisfiable.Because strings are a core data type in nearly every programming language, reliable and efficient solvers are essential in many areas of formal verification. This thesis studies methods for solving string constraints by reducing them to propositional logic, allowing the satisfiability check to be delegated to a SAT solver. After an introduction to the underlying logical frameworks, it first explores propositional encodings for regular constraints. Although the presented method is not expressive enough to handle meaningful problems, it motivates the following chapter, which develops a general procedure for solving quantifier-free formulas over different types of string constraints. Beyond the propositional encodings, the chapter also investigates how to select an adequate alphabet and how to effectively conclude unsatisfiability. Finally, the thesis concludes with a more formal treatment of string constraint solving by presenting a formalization of the theory in Isabelle, an interactive theorem prover
Sex-Specific Lifespan Extension and Anti-Obesogenic Effects of Salicornia europaea Extract Through Tor Signaling Modulation in Drosophila
Get PDFSome marine plants and algae are known to exert health benefits. However, the long-term effects and underlying mechanisms of these health benefits are still poorly understood. For this reason, we have investigated an extract from the marsh samphire Salicornia europaea for its life-prolonging potential. Methods: We investigated the effect of an aqueous extract of Salicornia europaea (SEE) on the lifespan of several wild-type strains of Drosophila. In addition, we used deficient flies to elucidate the mechanism of the life-prolonging effects. Finally, we comprehensively phenotyped the treated animals. Results: Supplementing a standard diet with SEE extended the lifespan of different Drosophila laboratory strains by up to a third (37% in w1118 and 19% in yw). A total of 0.05% of SEE were ineffective, whereas 0.2% induced robust lifespan prolongation. This effect was strictly sex-specific, as the SEE application was completely ineffective in males, while prolonging life in females. We found that the body fat content of SEE-treated female flies was lower compared to controls. The extract also positively impacted the lifespan of flies fed a high-fat diet but not a high-sugar diet. SEE exhibited a lipase-inhibitory activity in vitro. Moreover, SEE counteracted aging-associated loss of intestinal barrier integrity. The sex-specific lifespan extensions induced by the SEE entirely depended on functional Tor signaling in the flies. Tissue-specific silencing of the Tor signaling pathway in different cellular compartments of the intestine reduced, but did not altogether abolish, the lifespan-prolonging effect in females. SEE is a promising candidate for a health-promoting intervention, as it induces lifespan-prolonging and anti-obesogenic effects in a sex-specific manner. These effects depend on functional Tor and partially on FoxO signaling. Future studies should identify the active compounds in the extract
The evolutionary dynamics and functional role of the REPIN-RAYT system in the hut locus of Pseudomonas fluorescens SBW25
Get PDFMobile genetic elements (MGEs) shape bacterial genomes but often degenerate or vanish. In contrast, the REPIN-RAYT system, composed of repetitive extragenic palindromic doublets forming hairpins (REPINs) and REP-associated tyrosine transposases (RAYTs), is widespread and persists. REPINs can form hairpin structures and affect gene regulation, while RAYTs resemble housekeeping genes. The system is thought to provide a fitness benefit, though mechanisms remain unclear. In Chapter 3, I examined the evolutionary dynamics of RAYTs in Pseudomonas fluorescens SBW25 and related strains, focusing on the histidine utilization (hut) locus. I found that horizontal transfer of RAYTs occurs more often than assumed and that RAYTs can associate with multiple REPIN groups. Six REPIN sites in the hut locus were conserved across strains, though sequences varied depending on the RAYT present. In Chapter 4, I tested REPIN function using deletion mutants. Loss of REPIN RH, located between hutH2 and hutTh, caused reduced fitness early in competition but increased fitness later. RT-qPCR indicated that REPIN RH downregulates these genes, explaining the dynamic phenotype. Deletion of RAYTs had no detectable effect. In Chapter 5, I explored the role of hutD, a gene of unclear function. ΔhutD populations evolved for ~200 generations showed increased fitness. Genome sequencing revealed adaptive changes mainly in motility and biofilm genes, suggesting environmental adaptation rather than compensation for hutD loss. Overall, my work shows that REPINs can modulate gene expression and bacterial fitness, and that the REPIN-RAYT system is more dynamic than previously recognized. These findings highlight REPINs as regulatory elements and advance understanding of the hut locus
Simultaneous profiling of the blood and gut T and B cell repertoires in Crohn's disease and symptomatic controls illustrates tissue-specific alterations in the immune repertoire of individuals with Crohn's disease
Get PDFIntroduction Crohn's disease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome. We have previously shown that the T cell repertoire of individuals with CD harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology. Methods We simultaneously profiled the αβ and γδ T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa of 27 treatment-naïve individuals with CD and 27 age-matched symptomatic controls. Results Regardless of disease status, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of individuals with CD relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa. These include a depletion of mucosal-associated invariant T (MAIT) cells and an expansion of TRAV29/DV5-TRAJ5 + clonotypes in the blood repertoire of individuals with CD. Also, a significant depletion of multiple IGHV3-33-IGHJ4+ and IGHV3-33-IGHJ6+ clonotypes in the blood and gut IGH repertoire of individuals with CD. Discussion Our findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues as not all disease-induced alterations will be detected in the blood
Fusionsproteine aus TRAIL und tumorzellgerichteten Antikörpern zur Beseitigung maligner B-Zellen
Get PDFDie Therapie der akuten B-lymphatischen Leukämie (B-ALL) hat in den letzten Jahrzehnten deutliche Fortschritte gemacht, insbesondere durch zielgerichtete Wirkstoffe wie monoklonale Antikörper, small molecules und CAR-T-Zell-Therapien. Dennoch sprechen nicht alle Patient*innen gut auf die Therapien an, Rezidive/ Nebenwirkungen bleiben ein Problem und neue, gut verträgliche Therapiestrategien werden benötigt. CD19 wurde aufgrund seines günstigen Expressionsmusters als attraktives Zielantigen für die Therapie der B-ALL identifiziert. Native CD19-gerichtete Antikörper zeigten jedoch nur begrenzte Wirksamkeit. Ein Ansatz zur Wirkungssteigerung besteht in der Kopplung der Antikörper mit zelltodinduzierenden Substanzen. Besonders interessant ist die Fusion von Antikörpern mit humanen Liganden für Todeszeptoren wie TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), welcher Apoptose in Tumorzellen auslöst. In dieser Arbeit wurde das hochaktive Fusionsprotein CD19-scTRAIL entwickelt, bestehend aus einem CD19-IgG1-Antikörper und einer optimierten, einzelkettigen Variante von drei in Reihe angeordneten TRAIL-Untereinheiten (scTRAIL). Dazu wurden entsprechende Expressionsvektoren kloniert und das Protein erfolgreich exprimiert und gereinigt. Durchflusszytometrisch ließ sich eine spezifische, antigenabhängige Bindung von CD19-scTRAIL an CD19-positive B-ALL-Zelllinien nachweisen. Funktionell induzierte CD19-scTRAIL bereits in niedrigen nanomolaren Konzentrationen potenten Zelltod in zwei etablierten B-ALL-Zelllinien in vitro. Dieser pro-apoptotische Effekt war streng abhängig von der Bindung an CD19 auf den B-ALL-Zellen. Die Ergebnisse verdeutlichen das therapeutische Potenzial CD19-gerichteter TRAIL-Fusionsproteine, die künftig eine tumorspezifische und gut verträgliche Therapieoption für die B-ALL darstellen könnten
Untersuchungen zum klinischen Verlauf und zur postoperativen Lebensqualität von adulten Patienten mit Weichteil- und Knochensarkomen
Get PDFAufgrund der Seltenheit von Sarkomen kommt es häufig zu ungeplanten Operationen (UE). Es besteht Uneinigkeit über die notwendigen Sicherheitsabstände bei R0-Resektion. Die Datenlage zu Funktion und Lebensqualität (QoL) ist unzureichend, insbesondere nach UE und in Bezug auf Resektionsabstände. Ziel war die Analyse von Krankheitsverläufen bei Weichteilsarkomen (STS) und Knochensarkomen (BS) am UKSH Kiel sowie die Identifikation prognostischer Faktoren für STS. Zudem sollte der Einfluss von UE und Resektionsabständen (≤1 mm vs. >1 mm) auf onkologische und funktionelle Ergebnisse untersucht werden. Die Datenerhebung erfolgte retrospektiv mit prospektiver Blickrichtung bei 95 STS- und 16 BS-Patienten mit mindestens 6-monatiger Nachbeobachtung. Überlebenszeitanalysen wurden mittels Kaplan-Meier, Logrank-Test und Cox-Regression durchgeführt. Funktion und QoL wurden mit TESS- und EORTC-QLQ-C30-Fragebögen erhoben. Die 2-Jahres-Überlebensraten lagen bei STS bei 85 % (OS), 77 % (MFS) und 72 % (LRFS). Ein G3-Grading war mit einem 1,99-fach erhöhten Mortalitäts- und 2,65-fach erhöhten Metastasierungsrisiko assoziiert; ein Alter <70 Jahren bei Erstdiagnose mit einem 3,09-fach erhöhten Metastasierungsrisiko. UE führten zu mehr Operationen, jedoch nicht zu schlechterem OS, MFS, LRFS oder reduzierter QoL. Resektionsabstände bei R0-Resektion hatten keinen signifikanten Einfluss auf onkologische oder funktionelle Ergebnisse. Biologische Faktoren (G3-Grading, Alter <70) stellen wesentliche negative Prognoseparameter dar. Behandlungsspezifische Faktoren wie Resektionsabstände oder UE beeinflussen das Outcome bei adäquater Therapie im Sarkomzentrum nicht. Schmale Ränder ≤1 mm sind im multimodalen Therapiekonzept vertretbar. UE sollten dennoch vermieden werden, da sie Operationsanzahl, Morbidität und Belastung des Gesundheitssystems erhöhen