Gutenberg Open Science (Univ. Mainz)
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Einfluss der Phosphoinositid-Biosynthese auf Lokalisation und Toxizität von Alpha-Synuclein in Saccharomyces cerevisiae
No full text169 Seiten ; Illustrationen, Diagramm
Early recurrence of atrial arrhythmia following catheter ablation of atrial tachycardia consecutive to ablation of atrial fibrillation using the updated blanking period
No full textBackground:
In patients undergoing catheter ablation of atrial fibrillation (AF), arrhythmia recurrence during the blanking period is usually not considered a failure of treatment. The prognostic significance of early recurrence (ER) of atrial arrhythmia after ablation of atrial tachycardia (AT) subsequent to AF ablation is less certain.
Objective:
This study aimed to explore the association between early and late recurrence of atrial arrhythmia after ablation of AT subsequent to AF ablation.
Methods:
Patients undergoing a first ablation of AT subsequent to AF ablation between 2015 and 2021 were included in this retrospective, single-center, observational cohort study. Recurrent atrial arrhythmia was defined as AT or AF lasting more than 30 seconds. Regression models were built to assess the association between early (within 56 days) and late (beyond 56 days) recurrence of AT.
Results:
A total of 194 patients were included (mean age 67 ± 10 years, 63% male), of whom 71 (37%) had pulmonary vein isolation only, and 123 (63%) had received complex AF ablation during their index procedure. Fifty-two patients (27%) had ER of atrial arrhythmia. During a mean follow-up of 23.6 ± 15.5 months, 118 patients (61%) had late recurrence of atrial arrhythmia (111 with AT, 7 with AF). ER was associated with late recurrence (hazard ratio 1.53; 95% confidence interval 1.05–2.34; P = .02).
Conclusion:
One in 4 patients undergoing catheter ablation of AT subsequent to AF ablation had recurrent atrial arrhythmia within 56 days after ablation. ER was associated with late recurrence of atrial arrhythmia
Neue Syntheserouten und -methoden zur Herstellung von N-Heterozyklen für Pharmaka und mRNA-Therapeutika
No full textDie vorliegende Arbeit befasst sich mit drei unterschiedlichen Themenbereichen: Im ersten Teil wird
sich mit der Ausarbeitung neuer Synthesewege für bestehende N-heterozyklische Pharmazeutika und
pharmazeutischen Bausteinen befasst. Im zweiten Teil liegt der Fokus auf der Anwendung von
ω-Azidotriflaten in der Synthese von γ- und δ-Lactamen und im dritten Teil auf der Entwicklung
kationisch ionisierbarer Lipide für den mRNA-Transport in Lipid Nanopartikeln (LNP).
Bei der Entwicklung neuer Synthesewege für Pharmazeutika lag der Fokus zunächst darauf, eine neue
und innovative Synthese für das Benzodiazepin Midazolam auszuarbeiten. Dabei sollte eine möglichst
kurze Route mit einer guten Atomökonomie entwickelt werden. Zuerst werden unterschiedliche
Syntheseansätze und dann die erfolgreich erarbeite Syntheseroute für Midazolam durch eine MICHAEL-Addition gefolgt von einer Zyklisierung zum Siebenring durch eine Reduktion gezeigt.
Im folgenden Kapitel werden die Versuche zur Substitution von Bromacetonitril in der Synthese eines
Fragmentes des Coronamedikaments Nirmatrelvir beschrieben. Dabei wurden viele synthetisierte und
kommerziell erhältliche Reagenzien zur Substitution von Bromacetonitril getestet. Schließlich wurde
eine Synthesestrategie entwickelt, die Bromacetonitril durch 2-Azidoethyltrifluormethansulfonat
ersetzt und eine innovative Flow-Reduktion zur Synthese des Nirmatrelvirbausteins Methyl (S)-2-((tert-butoxycarbonyl)amino)-3-((S)-2-oxopyrrolidin-3-yl)propanoate beinhaltet.
Im zweiten Teil wird die erarbeitete Methode zur Synthese des Nirmatrelvirbausteins aufgegriffen und
daraus eine neue Methode zur Synthese von 3-substituierten Pyrrolidonen und Piperidonen
entwickelt. Dabei wurden Methylester über eine α-Alkylierung mit 2-Azidoethyltrifluormethansulfonat
oder 3-Azidopropyltrifluormethansulfonat zu Azidoestern umgesetzt und durch eine Reduktion zum
Amin zum jeweilige δ-Lactam oder γ-Lactam zyklisiert. Es wird die Optimierung der Methode und das
getestete Substratspektrum gezeigt.
Der dritte Teil dieser Arbeit beschäftigt sich mit der Entwicklung neuer kationisch ionisierbarer Lipide
mit Pyridinen und Benzolen als „Tail-junction“. Des Weiteren lag der Fokus darauf Schwefel in die
„Tails“ der Lipide einzubauen. Die Lipide wurden im Rahmen des KIWI-Projektes vom Projektpartner
bei BioNTech in bereits bestehenden LNP-Formulierungen verwendet und hinsichtlich ihrer Fähigkeit
mRNA zu transportieren getestet. Anhand der Ergebnisse der Biotests wurden die Strukturen der
Lipide als Teil des ZiEL-Unterprojektes weiterentwickelt.XIII, 423 Seiten ; Illustrationen, Diagramm
Electrochemical hydrodehalogenation based on 3D-printed electrodes
No full textAdditive manufacturing has emerged as a versatile platform for electrode fabrication, offering cost efficiency, design flexibility, and compatibility with a wide range of materials. Electrochemical dehalogenation represents a critical strategy for the removal of toxic halogenated organic pollutants, such as chloroacetic acids, which pose significant environmental and health risks. The use of earth-abundant metals, including iron, copper, and nickel, as well as carbon-based materials, further enhances the sustainability and scalability of this approach. This concept article describes the electrochemical reduction of trichloroacetic acid at conventional electrodes and reviews the current state of research on electrochemical dehalogenation at additively manufactured electrodes. From this perspective, the further integration of advanced fabrication techniques, along with the application of machine learning and artificial intelligence, presents significant opportunities for innovation in materials and processes. In addition to electrode fabrication, the incorporation of in situ spectroscopy is proposed to gain deeper insight into the underlying reaction mechanisms. To bridge the gap between fundamental research and the implementation of new processes in industrial applications, a series of process optimization strategies is also outlined
Interaction of tumor cells and cancer-associated fibroblasts in radiation-induced senescence
No full text25 Seiten ; Illustratione
Sicherheit und Effektivität der peroralen endoskopischen Myotomie an Ösophagus und Magen
No full text70 Seiten ; Illustrationen, Diagramm
The translation and validation of the procrastination and precrastination traits scale in the modern Arabic Language
No full textProcrastination and precrastination are distinct self-regulatory behaviors that influence individual functioning and well-being. Despite growing interest in these constructs, culturally adapted and psychometrically validated tools in Arabic-speaking contexts remain limited. This study addresses this gap by translating, validating, and evaluating the psychometric properties of the Arabic version of the Procrastination and Precrastination Traits Scale (PPTS). The present study aimed to examine the factorial structure, reliability, and convergent and divergent validity of the Arabic PPTS among Arabic-speaking adults and explore its associations with life satisfaction and standardized measures of procrastination. A sample of 1,000 participants (mean age = 27.93 years, standard deviation (SD) = 5.73; age range = 18–38) completed an online survey comprising the 18-item PPTS, the 12-item Pure Procrastination Scale (PPS), and the 5-item Satisfaction with Life Scale (SWLS). Descriptive analyses, confirmatory factor analysis (CFA), reliability testing, and bivariate correlations were conducted to assess psychometric performance. CFA supported a two-factor model with good fit indices (CFI = 0.939; TLI = 0.930; RMSEA = 0.05; SRMR = 0.04). All the items loaded significantly onto their respective factors: procrastination (items 1–10) and precrastination (items 11–18). Internal consistency was good for both subscales (procrastination: α = 0.861, ω = 0.861; precrastination: α = 0.788, ω = 0.803). Procrastination was positively correlated with PPS (r = 0.781, p < 0.001) and negatively correlated with SWLS (r = -0.475, p < 0.001). Conversely, precrastination was negatively associated with PPS (r = -0.405, p < 0.001) and positively associated with SWLS (r = 0.249, p < 0.001), supporting both convergent and divergent validity. The Arabic PPTS has adequate factorial validity, good reliability, and meaningful construct validity. It provides a culturally appropriate instrument for assessing behavioral tendencies of delay and hastiness, with implications for psychological assessment, educational interventions, and cross-cultural research on self-regulation and well-being
Die Rolle der Weiterbildung in der Ära von New Work : Perspektiven auf die Bedeutung von Lernen in der Personalentwicklung
No full textTransformationsprozesse wie Digitalisierung und demografischer Wandel verändern die Arbeitsrealität und fordern individuelle Selbstorganisation. New Work/New Learning markieren dabei ein neues Verhältnis von Arbeit und Mensch – mit Fokus auf Flexibilität und Selbststeuerung. In diesem Kontext gewinnt die betriebliche Weiterbildung an Bedeutung, um Transformationsprozesse zu begleiten, wobei die Personalentwicklung eine zentrale Rolle im Schnittfeld von Arbeit und Lernen spielt. Die Diskussion um New Work und New Learning wird oft aus einer (betriebs-)wirtschaftlichen Perspektive geführt, während die Erwachsenenbildung, obwohl betroffen, weniger thematisiert wird. Dieser Beitrag untersucht das Verständnis von Lernen im Rahmen von New Work-Konzepten und die Bedeutung von Weiterbildung als Instrument zur Gestaltung struktureller Veränderungen. Dies wird durch problemzentrierte Interviews mit Personalentwickler:innen und eine qualitative Inhaltsanalyse erreicht
Direct interaction between TDP-43 and Tau promotes their co-condensation, while suppressing Tau fibril formation and seeding
No full textNeuronal aggregates of Tau are a hallmark of Alzheimer’s disease (AD), but more than half of the patients exhibit additional TDP-43 inclusions, while some have co-aggregates of the two proteins. The presence of such co-aggregates is associated with increased disease severity, although whether there is a causal relationship remains unclear. Here, we demonstrate that Tau and TDP-43 mutually promote each other’s condensation through direct interaction in vitro, forming irregularly-shaped or multiphasic co-condensates with lower TDP-43 mobility, but higher Tau mobility. While Tau promotes TDP-43 aggregation in vitro, TDP-43 suppresses formation of Tau fibrils and instead causes formation of oligomeric Tau and Tau/TDP-43 species. These co-assemblies hinder Tau seeding in a biosensor assay specific for proteopathic Tau seeds. Consistent with these data, insoluble material extracted from AD patient brains with Tau/TDP-43 co-aggregates exhibits reduced Tau seeding compared to AD patient brains with Tau aggregates only. In contrast, patient-derived extracts from AD patient brains with Tau/TDP-43 co-aggregates are highly potent in seeding new TDP-43 aggregates in a TDP-43 reporter cell line. Our results suggest that direct interaction between TDP-43 and Tau may suppress Tau pathology, while promoting TDP-43 pathology in Alzheimer’s disease patients
Reconfigurable transient polymer networks based on heteroleptic metal–ligand complexes
No full textWe present a polymer network platform based on metal–ligand complexes that enables reconfiguration through the sequential introduction of polymeric ligands and metal ions. Using tetraPEG functionalized with sterically demanding and slim ligands, we demonstrate four network states. However, the interference from competitive parallel complexations is reflected in rheology as additional relaxation modes. A simple kinetic model rationalizes the extent of reconfiguration as a function of thermodynamic preference, revealing the critical role of competitive complexation. DFT calculations confirm that ligand denticity stabilizes heteroleptic complexes and drives the reconfiguration pathway. Together, experiment, modeling, and computation establish a comprehensive framework for designing reconfigurable transient polymer networks