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Aktuellste Veröffentlichungen

Metal-triggered topology switching in bipyridine-modified DNA G-quadruplexes
(Oxford University Press (OUP), 2026-07-28) Durmisevic, Armin; Openy, Joseph; Majid, Aatikah; Nanda, Mrunal; Vilar, Ramon; Clever, Guido H
Gaining control over DNA G-quadruplex topology bears potential to modulate and study their interaction with other biomacromolecules such as proteins. To achieve this, we introduced bipyridine ligands into short oligonucleotide strands derived from telomeric regions of humans and Tetrahymena as well as into an oncogenic promoter region capable of forming such G-quadruplexes. This modification makes it possible to dynamically access different G-quadruplex topologies through the formation of chelate complexes within the quadruplex loop regions using metals such as Cu2+, Ni2+, Zn2+, Co2+, and Cd2+. The metal-coordinated systems show enhanced stability towards thermal denaturation as well as a solvation-related response in the presence of molecular crowding reagents. Interestingly, these G-quadruplexes modified with bipyridine-metal complexes stay folded in cellulo and therefore show potential for creating new oligonucleotide-based diagnostic agents and therapeutics. Metal-stabilized G-quadruplexes could therefore be suitable as probes to explore protein-G4 interactions, as inducers for G4-dependent cellular processes, or decoys to sequester transcription factors.
Vocabulary and expressive morpho-syntax in individuals with Down syndrome: links to narration
(Elsevier BV, 2024-07-21) Neitzel, Isabel
Background: Narrative ability is crucial for social participation in everyday and school life but involves different language abilities such as vocabulary and morpho-syntax. This is particularly difficult for individuals who display both language and cognitive impairments. Previous research has identified productive vocabulary as a possible key factor for narrative performance in in- dividuals with Down syndrome. Considering a close connection between lexical and morpho- syntactic performance within language acquisition and the distinct impairments that in- dividuals with Down syndrome display concerning their morpho-syntactic skills, the nature of a relation between vocabulary and narrative skills under the influence of grammatical deficits re- quires further investigation. Methods: Narrations were obtained from 28 children and adolescents with Down syndrome (aged 10;0–20;1) using a non-verbal picture book. Narrative abilities were rated using the Narrative Scoring Scheme across seven narrative aspects (including macro- and microstructure). Vocabulary analyses and morpho-lexical context analyses including verb and conjunction enumerations, evaluation of verb position and MLU were conducted. Findings from the transcript analysis have been supplemented with data from standardized language measures evaluating expressive lexical and morpho-syntactic development. A multiple regression analysis was conducted to identify significant predictors for narrative outcome in the participants with Down syndrome. Results: Lexical analyses revealed a high heterogeneity in production of subordinating conjunc- tions as a link between lexical and morpho-syntactic abilities. Comparisons of standardized and narrative data demonstrated differences in subordinate clause production depending on the elicitation setting. A multiple regression analysis identified the number of different verbs in the narrative task as the most significant predictor for narrative performance in individuals with Down syndrome. Discussion and implications: The findings of this study contribute to the knowledge regarding factors that influence narrative performance in individuals with language impairment. A differ- entiated verb lexicon can be identified as the key ability for reaching advanced narrative skills in participants with Down syndrome. These findings are of clinical relevance for therapeutic and educational support and contribute to an understanding of the relation between strengths in vocabulary and morpho-syntactic weaknesses in individuals with Down syndrome within communicative participation.
Influence of cosolvents on the pressure stability of human serum albumin
(Wiley, 2024-11-04) Savelkouls, Jaqueline; Schneider, Eric; Woo, Chang Hee; Paulus, Michael
A small-angle X-ray scattering study on the pressure-dependent behavior of human serum albumin (HSA) is presented. HSA is able to absorb cosolvents such as drugs or other hydrophobic substances and transport them, for example, in the human body. It is shown that the uptake of various substances is associated with increased pressure stability, which can be used as an indicator of protein–substance interaction. Especially the interaction between the substances and the hydrophobic pockets of the protein is an important aspect, which mainly depends on the hydrophobicity as well as the size of the used cosolvents. Specifically, drugs such as ibuprofen and theophylline increase the pressure stability of the protein enormously, while caffeine or TMAO, for example, has no strong influence.
Voltage stability analysis of grid-forming converters with current limitation
(Elsevier BV, 2024-06-28) Liemann, Sebastian; Rehtanz, Christian
In this paper, a systematic short- and long-term voltage stability analysis of grid-forming converters with current limitations is conducted. For this, sampling studies are performed in an aggregated version of the Nordic test system. Here, the grid-forming control approach, the simulation type (EMT/phasor), current prioritisation and load composition are varied. Also, a stability-enhancing control method is developed to stabilise the converter during current limitation. The proposed method does not require any parameter tuning and can be applied to almost all grid-forming approaches. Its performance is demonstrated by comparing it to similar methods. The results show that the proposed method can greatly improve short- and long-term voltage stability for all investigated grid-forming approaches. In addition, accurate load models are crucial, as small modelling differences can have a greater impact on stability than the choice of simulation type. Here, both simulation types show the same voltage dynamics but have small differences in the stability limits.
Yet another Bayesian active learning reliability analysis method
(Elsevier BV, 2024-09-20) Dang, Chao; Zhou, Tong; Valdebenito, Marcos A.; Faes, Matthias G.R.
The well-established Bayesian failure probability inference (BFPI) framework offers a solid foundation for developing new Bayesian active learning reliability analysis methods. However, there remains an open question regarding how to effectively leverage the posterior statistics of the failure probability to design the two key components for Bayesian active learning: the stopping criterion and learning function. In this study, we present another innovative Bayesian active learning reliability analysis method, called ‘Weakly Bayesian Active Learning Quadrature’ (WBALQ), which builds upon the BFPI framework to evaluate extremely small failure probabilities. Instead of relying on the posterior variance, we propose a more computationally feasible measure of the epistemic uncertainty in the failure probability by examining its posterior first absolute central moment. Based on this measure and the posterior mean of the failure probability, a new stopping criterion is devised. A recently developed numerical integrator is then employed to approximate the two analytically intractable terms inherent in the stopping criterion. Furthermore, a new learning function is proposed, which is partly derived from the epistemic uncertainty measure. The performance of the proposed method is demonstrated by five numerical examples. It is found that our method is able to assess extremely small failure probabilities with satisfactory accuracy and efficiency.