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We provide here the sub-clustering results for each major cell type forthe manuscript: Kuppe, Ramirez Flores, Li et al. "Spatial multi-omic map of human myocardial infarction", 2022. The cells from snRNA-seq and snATAC-seq were first integrated and then sub-clustering was performed based on the integrated data. We tried our best to annotated the obtained sub-clusters.

We provide here the raw data of visium forthe manuscript: Kuppe, Ramirez Flores, Li et al. "Spatial multi-omic map of human myocardial infarction", 2022

Thrombus formation and thromboembolic events play important roles in various cardiovascular pathologies. The key receptor involved in platelet aggregation is the fibrinogen receptor glycoprotein IIb/IIIa. [18F]GP1, a derivative of the GPIIb/IIIa antagonist elarofiban, is a specific 18F-labeled small-molecule radiotracer that binds with high affinity to GPIIb/IIIa receptors of activated platelets. An improved, robust and fully automated radiosynthesis of [18F]GP1 has been developed. [18F]GP1 has been synthesized with decay corrected radiochemical yields of 38 ± 6%, with a radiochemical concentration up to 1900 MBq/mL, molar activities of 952–9428 GBq/µmol and a radio-chemical purity &gt, 98%. After determination of the optimal reaction conditions, in particular for HPLC separation, adaption of the reaction conditions to PET center requirements, validation of the manufacturing process and the quality control methods, the synthesis of [18F]GP1 was successfully implemented to GMP standards and was available for clinical application. We describe the GMP-compliant synthesis of the novel radiotracer [18F]GP1. Moreover, we provide some proof-of-concept examples for clinical application in the cardiovascular field. PET/CT with the novel small-molecular radiotracer [18F]GP1 may serve as a novel highly sensitive tool for visualizing active platelet aggregation at the molecular level.

A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them \(\it TTN\) and \(\it RBM20\). Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in \(\it TTN\) (\(\it TTN\)tv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing factor RNA binding motif protein 20 (\(\it RBM20\)) are also known to be associated with severe cardiomyopathies. \(\it TTN\) is one of the major \(\it RBM20\) splicing targets. Most of the pathogenic \(\it RBM20\) mutations are localized in the highly conserved arginine serine rich domain (RS), leading to a cytoplasmic mislocalization of mutant \(\it RBM20\). Here, we present a patient with an early onset DCM carrying a combination of (likely) pathogenic \(\it TTN\) and \(\it RBM20\) mutations. We show that the splicing of \(\it RBM20\) target genes is affected in the mutation carrier. Furthermore, we reveal \(\it RBM20\) haploinsufficiency presumably caused by the frameshift mutation in \(\it RBM20\).

Cardiomyopathies might lead to end-stage heart disease with the requirement of drastic treatments like bridging up to transplant or heart transplantation. A not precisely known proportion of these diseases are genetically determined. We genotyped 43 index-patients (30 DCM, 10 ARVC, 3 RCM) with advanced or end stage cardiomyopathy using a gene panel which covered 46 known cardiomyopathy disease genes. Fifty-three variants with possible impact on disease in 33 patients were identified. Of these 27 (51%) were classified as likely pathogenic or pathogenic in the \(\textit {MYH7, MYL2, MYL3, NEXN, TNNC1, TNNI3, DES, LMNA, PKP2, PLN, RBM20, TTN,}\) and \(\it CRYAB\) genes. Fifty-six percent (n = 24) of index-patients carried a likely pathogenic or pathogenic mutation. Of these 75% (n = 18) were familial and 25% (n = 6) sporadic cases. However, severe cardiomyopathy seemed to be not characterized by a specific mutation profile. Remarkably, we identified a novel homozygous \(\it PKP2\)-missense variant in a large consanguineous family with sudden death in early childhood and several members with heart transplantation in adolescent age.

Nowadays there already exists a large amount of driving-related information displayed in the dashboard and thus additional information concerning ecological driving might enlarge the workload of the driver further. This raises the question whether the presentation of additional ecologic information via the haptic channel is more efficient and comfortable for the driver compared to a visual presentation. Previous studies proved the impact of driver feedback systems on the reduction of fuel consumption. However, most of the studies only dealt with visual displays. Thus in the present study a visual, a haptic, and a visual-haptic interface were designed for an acceleration and a gear shift advice system. Subsequently their impact on the acceleration and the gear shift behavior of the driver as well as their subjective acceptance were compared. Results showed that especially the combination of the visual and haptic modality led to the fastest reaction times and smallest deviations from the optimal acceleration and gear shift behavior. However, concerning the acceptance participants preferred the visual display.

Ziel der Arbeit war die Gewinnung neuer Erkenntnisse über die Funktionsgestaltung von Fahrerassistenzsystemen, die zur Verbesserung ihrer Wirksamkeit und Akzeptanz beitragen. Psychologische Modelle zum Fahrverhalten identifizieren die Anforderungen einer Fahraufgabe als wesentlich für die Fahrleistung. Dieses legt die Abstimmung des Assistenzsystems mit den Anforderungen als Möglichkeit zur Verbesserung der Fahrerunterstützung nahe. In 4 Studien zur Längs- und Querführung wurde untersucht, ob mit den Anforderungen abgestimmte Assistenzsysteme zu einer verbesserten Wirksamkeit und Akzeptanz im Vergleich zu nicht abgestimmten Systemen führen. In den Studien waren aufgrund der Aufgabenanforderungen entweder die Informationsaufnahme, die Handlungsplanung oder die Handlungsausführung des Fahrers erschwert. Unterstützung erhielten die Probanden durch 3 verschiedene Assistenzsysteme. Der Info-Assistent unterstützte die Informationsaufnahme, der Warn-Assistent die Handlungsplanung und der Eingriff die Handlungsausführung. Somit unterstützte in jeder Studie ein Assistenzsystem gezielt bei der erschwerten Anforderung und wurde aufgrund dieser Abstimmung als das hilfreichste System vermutet. Die Wirkung der Assistenten wurde anhand der Fahrleistung, Akzeptanz und Beanspruchung erhoben. Die Ergebnisse zeigen, dass das Konzept der Abstimmung von Assistenzfunktionen mit den Aufgabenanforderungen grundsätzlich sinnvoll erscheint. Es zeigte sich außerdem, dass die genauen Schwierigkeiten, die sich aufgrund der Anforderungen für den Fahrer ergeben, noch differenzierter für verschiedene Situationen untersucht werden sollten. Für die Entwicklung von Assistenzsystemen bedeuten die Ergebnisse, Fahrerassistenzsysteme möglicherweise mit mehreren anstelle nur einer Funktion auszustatten und diese je nach wechselnden Anforderungen zu aktivieren. Ferner könnte der Ansatz als Basis für ein Modell zur Vorhersagbarkeit der wirksamsten Assistenzfunktion dienen., The goal of this research was to get some basic findings about the functional design of driver assistance systems, which can be helpful to improve their safety benefits and acceptance. Psychological models regarding driver behavior identify the task demands as an essential factor for driving performance. This suggests to coordinate the function of the driver assistance system with the task demands to improve driver support. In 4 studies regarding the longitudinal and lateral control of the car was analyzed if driver assistance systems which are coordinated with the task demands result in a better driving performance and higher acceptance evaluations compared to not-coordinated systems. In each study the driver was either impaired in his or her information acquisition, action planning or action execution because of the given task demands. Drivers were assisted by 3 different concepts of driver assistance systems. The Info-Assistant supported the information acquisition, the Warning-Assistant supported the action planning and the Intervention-Assistant supported the action execution. Hence in each study one driver assistance system supported specifically the difficult task demands and was expected to be the most useful system. Systems were evaluated by using data regarding driving performance, acceptance and workload. The results show that the idea of coordinating the assistance function with the existing task demands seems to be basically reasonable. Moreover, it was shown that the difficulties for the driver resulting from the task demands need to be analyzed in more detail for different situations. For the development of driver assistance systems the results imply to equip systems possibly with several functions instead of just one and to activate one of these functions according to the current task demands. Furthermore the findings could be used as a basis to build a model for the prediction of the most useful assistance function depending on the task demands., Berichte aus dem DLR-Institut für Verkehrssystemtechnik, vol. 14