Stereoselektive Synthese von Sphingolipiden zur Inhibierung der Degranulation von Mastzellen

Die Degranulation von Mastzellen soll durch Glycosphingolipide, welche mit der Zellmembran wechselwirken inhibiert werden. Der Sphingosingrundkörper wurde in zehn-stufigen Synthese ausgehend von N-Boc-Serin, aufgebaut. Die anschließende Glycosylierung erfolgte nach der Trichloracetimidatmethode in sehr guten Ausbeuten und stellte den Schlüsselschritt dar. Durch die Variation von unter Anderem der Amidseitenkette, der Glycosylkopfgruppe und des Sphingosingrundkörpers wurde eine Vielzahl an Derivaten für das Screening im Degranulationsassay bereitgestellt.The present dissertation covers the synthesis of glycosphingolipids which interact with the cell membrane in order to inhibit the degranulation of mast cells. The sphingosin body was synthesized in ten steps starting from N-Boc-Serin. The key step, the glycosylation was achieved using the trichloracetimidat method. The variation of the amid sidechain, the gylcosyl headgroup and the sphingosin body created a number of derivatives that were tested in the degranulation assay

Neural correlates of linguistic collocations during continuous speech perception

Language is fundamentally predictable, both on a higher schematic level as well as low-level lexical items. Regarding predictability on a lexical level, collocations are frequent co-occurrences of words that are often characterized by high strength of association. So far, psycho- and neurolinguistic studies have mostly employed highly artificial experimental paradigms in the investigation of collocations by focusing on the processing of single words or isolated sentences. In contrast, here we analyze EEG brain responses recorded during stimulation with continuous speech, i.e., audio books. We find that the N400 response to collocations is significantly different from that of non-collocations, whereas the effect varies with respect to cortical region (anterior/posterior) and laterality (left/right). Our results are in line with studies using continuous speech, and they mostly contradict those using artificial paradigms and stimuli. To the best of our knowledge, this is the first neurolinguistic study on collocations using continuous speech stimulation

Perceptions and attitudes of bicyclists towards self-driving cars: a mixed methods approach

Efforts to advance Autonomous Vehicles (AVs) have taken on a central role in research and development in recent years and will have a significant influence on road traffic in the future. Research on AVs has mainly focused on the technology itself and the direct users of AVs and their acceptance. However, the role of bicyclists, interacting with AVs in traffic, is not yet researched as thoroughly. Using a mixed methods approach, we combine quantitative results from a survey among bicyclists (N = 889) and qualitative results from a focus group (N = 19) to give insights into bicyclists’ attitudes and expectations towards self-driving cars. The results showed that bicyclists’ affinity for technology is a significant predictor for both their trust and perceived safety towards self-driving cars, as well as an effect of age and gender on these variables. Both from the quantitative and qualitative results, it is clear that flawless functioning of the technology of AVs is a prerequisite for bicyclists encountering and interacting with AVs in traffic, and that the status of the vehicle (autonomous vs. non-autonomous) is very important as well as easy to understand signals that indicate the next manoeuvres of the AV. For supporting interaction with AVs, we found that bicyclists are open to External Human Machine Interface (eHMI) solutions, as long as these ensure inclusion and support the easily-accessible nature of bicycling. Our findings can inform the design of eHMIs that help shape the interaction between bicyclists and AVs in the future, and provide insights on which factors determine the perception of AVs and, ultimately, the acceptance of AVs as part of road traffic

Lipidomimetic Compounds Act as HIV-1 Entry Inhibitors by Altering Viral Membrane Structure

The envelope of Human Immunodeficiency Virus type 1 (HIV-1) consists of a liquid-ordered membrane enriched in raft lipids and containing the viral glycoproteins. Previous studies demonstrated that changes in viral membrane lipid composition affecting membrane structure or curvature can impair infectivity. Here, we describe novel antiviral compounds that were identified by screening compound libraries based on raft lipid-like scaffolds. Three distinct molecular structures were chosen for mode-of-action studies, a sterol derivative (J391B), a sphingosine derivative (J582C) and a long aliphatic chain derivative (IBS70). All three target the viral membrane and inhibit virus infectivity at the stage of fusion without perturbing virus stability or affecting virion-associated envelope glycoproteins. Their effect did not depend on the expressed envelope glycoproteins or a specific entry route, being equally strong in HIV pseudotypes carrying VSV-G or MLV-Env glycoproteins. Labeling with laurdan, a reporter of membrane order, revealed different membrane structure alterations upon compound treatment of HIV-1, which correlated with loss of infectivity. J582C and IBS70 decreased membrane order in distinctive ways, whereas J391B increased membrane order. The compounds' effects on membrane order were reproduced in liposomes generated from extracted HIV lipids and thus independent both of virion proteins and of membrane leaflet asymmetry. Remarkably, increase of membrane order by J391B required phosphatidylserine, a lipid enriched in the HIV envelope. Counterintuitively, mixtures of two compounds with opposite effects on membrane order, J582C and J391B, did not neutralize each other but synergistically inhibited HIV infection. Thus, altering membrane order, which can occur by different mechanisms, constitutes a novel antiviral mode of action that may be of general relevance for enveloped viruses and difficult to overcome by resistance development

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Stereoselektive Synthese von Sphingolipiden zur Inhibierung der Degranulation von Mastzellen

Die Degranulation von Mastzellen soll durch Glycosphingolipide, welche mit der Zellmembran wechselwirken inhibiert werden. Der Sphingosingrundkörper wurde in zehn-stufigen Synthese ausgehend von N-Boc-Serin, aufgebaut. Die anschließende Glycosylierung erfolgte nach der Trichloracetimidatmethode in sehr guten Ausbeuten und stellte den Schlüsselschritt dar. Durch die Variation von unter Anderem der Amidseitenkette, der Glycosylkopfgruppe und des Sphingosingrundkörpers wurde eine Vielzahl an Derivaten für das Screening im Degranulationsassay bereitgestellt.The present dissertation covers the synthesis of glycosphingolipids which interact with the cell membrane in order to inhibit the degranulation of mast cells. The sphingosin body was synthesized in ten steps starting from N-Boc-Serin. The key step, the glycosylation was achieved using the trichloracetimidat method. The variation of the amid sidechain, the gylcosyl headgroup and the sphingosin body created a number of derivatives that were tested in the degranulation assay

Stereoselektive Synthese von Sphingolipiden zur Inhibierung der Degranulation von Mastzellen

Die Degranulation von Mastzellen soll durch Glycosphingolipide, welche mit der Zellmembran wechselwirken inhibiert werden. Der Sphingosingrundkörper wurde in zehn-stufigen Synthese ausgehend von N-Boc-Serin, aufgebaut. Die anschließende Glycosylierung erfolgte nach der Trichloracetimidatmethode in sehr guten Ausbeuten und stellte den Schlüsselschritt dar. Durch die Variation von unter Anderem der Amidseitenkette, der Glycosylkopfgruppe und des Sphingosingrundkörpers wurde eine Vielzahl an Derivaten für das Screening im Degranulationsassay bereitgestellt.The present dissertation covers the synthesis of glycosphingolipids which interact with the cell membrane in order to inhibit the degranulation of mast cells. The sphingosin body was synthesized in ten steps starting from N-Boc-Serin. The key step, the glycosylation was achieved using the trichloracetimidat method. The variation of the amid sidechain, the gylcosyl headgroup and the sphingosin body created a number of derivatives that were tested in the degranulation assay

Towards the Future of Sustainable Mobility: Results from a European Survey on (Electric) Powered-Two Wheelers

Personal transport is of high importance in our society and the 2020 pandemic situation has reinforced this situation. At the same time, transport contributes to local emissions, which need to be reduced in the face of climate change. Changing from vehicles with internal combustion engines to light electric vehicles could be one promising approach. Therefore, we need to understand mobility patterns and attitudes towards E-mobility to create sustainable transport solutions that will be broadly accepted. An online survey with N = 432 participants across Europe was conducted. The majority of respondents came from Germany, followed by Italy, Austria and Sweden. Generally, cars are the main vehicle for personal transport. PTWs are used for commuting as well as leisure activity. Driving experience, easier parking and lower maintenance compared to cars are major reasons to choose a PTW. No differences between younger and elderly participants were observed. E-PTWs are primarily avoided due to high costs, range anxiety and expected problems with the charging infrastructure. To support sustainable mobility, these obstacles need to be overcome. One aspect is definitely the provision of better charging infrastructure or electric vehicles with increased range. Hence, given typical trip lengths and purposes, it might seem equally important to tackle prejudices and increase the knowledge about E-mobility with all its potential benefits in the population

Factors Influencing and Contributing to Perceived Safety of Passengers during Driverless Shuttle Rides

This study investigates the perceived safety of passengers while being on board of a driverless shuttle without a steward present. The aim of the study is to draw conclusions on factors that influence and contribute to perceived safety of passengers in driverless shuttles. For this, four different test rides were conducted, representing aspects that might challenge passengers’ perceived safety once driverless shuttles become part of public transport: passengers had to ride the shuttle on their own (without a steward present), had to interact with another passenger, and had to react to two different unexpected technical difficulties. Passengers were then asked what had influenced their perceived safety and what would contribute to it. Results show that perceived safety of passengers was high across all different test rides. The most important factors influencing the perceived safety of passengers were the shuttle’s driving style and passengers’ trust in the technology. The driving style was increasingly less important as the passengers gained experience with the driverless shuttle. Readily available contact with someone in a control room would significantly contribute to an increase in perceived safety while riding a driverless shuttle. For researchers, as well as technicians in the field of autonomous driving, our findings could inform the design and set-up of driverless shuttles in order to increase perceived safety; for example, how to signal passengers that there is always the possibility of contact to someone in a control room. Reacting to these concerns and challenges will further help to foster acceptance of AVs in society. Future research should explore our findings in an even more natural setting, e.g., a controlled mixed traffic environment

Factors Influencing and Contributing to Perceived Safety of Passengers during Driverless Shuttle Rides

This study investigates the perceived safety of passengers while being on board of a driverless shuttle without a steward present. The aim of the study is to draw conclusions on factors that influence and contribute to perceived safety of passengers in driverless shuttles. For this, four different test rides were conducted, representing aspects that might challenge passengers’ perceived safety once driverless shuttles become part of public transport: passengers had to ride the shuttle on their own (without a steward present), had to interact with another passenger, and had to react to two different unexpected technical difficulties. Passengers were then asked what had influenced their perceived safety and what would contribute to it. Results show that perceived safety of passengers was high across all different test rides. The most important factors influencing the perceived safety of passengers were the shuttle’s driving style and passengers’ trust in the technology. The driving style was increasingly less important as the passengers gained experience with the driverless shuttle. Readily available contact with someone in a control room would significantly contribute to an increase in perceived safety while riding a driverless shuttle. For researchers, as well as technicians in the field of autonomous driving, our findings could inform the design and set-up of driverless shuttles in order to increase perceived safety; for example, how to signal passengers that there is always the possibility of contact to someone in a control room. Reacting to these concerns and challenges will further help to foster acceptance of AVs in society. Future research should explore our findings in an even more natural setting, e.g., a controlled mixed traffic environment