Modellierung von Kommunikationssystemen zum Zweck der Systemanalyse und des Systementwurfs

Einen wesentlichen Beitrag zu Innovationen und Weiterentwicklungen in der Automobilindustrie leisten elektronische Komponenten. Der funktionale Wachstum in den Bereichen Sicherheit, Komfort und Fahrerassistenz führt zu einer Erhöhung der Komplexität. Neben der Anzahl der Komponenten steigert sich auch der Bedarf an Kooperation und Datenaustausch. Insbesondere by-wire- und Assistenzsysteme (Hochautomatisiertes Fahren) zeichnen sich durch hohe Anforderungen in den Bereichen Zuverlässigkeit, Datenkonsistenz, Fehlertoleranz und Ausfallsicherheit aus. Die Zusammenarbeit einzelner Steuergeräte fordert von der Kommunikationsstruktur neben hohen Datenraten auch Determinismus und Echtzeitverhalten. Die Entwicklung dieser komplexen verteilten Systeme profitiert durch modellbasierte Entwurfsprozesse. Der Nachweis von grundlegenden Systemeigenschaften mit dem Schwerpunkt Kommunikation soll bereits in frühen Entwurfsphasen mit Hilfe von ausführbaren Spezifikationen modell- und simulationsbasiert erfolgen. In dieser Arbeit wird ein Modellierungsansatz entworfen, welcher die typischen ereignis- und zeitgesteuerten Protokolle in der Domäne Automotive adressiert. Der Fokus liegt auf den Buszugriffsverfahren. Modelle auf unterschiedlichen Abstraktionsebenen werden am Beispiel von Controller Area Network (CAN) und FlexRay definiert und realisiert. Neben der reinen Kommunikation werden die angrenzenden Themenfelder Gateway (heterogene Kopplung) und Betriebssystem berücksichtigt. Detaillierte Modelle eignen sich zur Analyse spezifischer Protokolleigenschaften sowie zur Weiterentwicklung von Protokollfunktionen auf Modellebene. Mit abstrakteren Modellen lassen sich Leistungs- und Eigenschaftsanalysen von großen heterogenen Systemen durchführen. Echtzeitkommunikation, vernetzte Systeme und Anwendungsfelder für modellbasierte Entwurfsprozesse finden sich auch außerhalb des Automobilbereiches. Die Anwendung wird am Beispiel der Entwicklung und Optimierung eines komplexen verteilten Systems zur Steuerung einer Nanopositionier- und Nanomessmaschine demonstriert. Innerhalb des Entwicklungsprozesses werden Entwurf, Realisierung und Leistungsbewertung bezüglich der Architektur des Gesamtsystems, der Verteilung von Funktionen und der Realisierung einzelner Komponenten sowie applikationsspezifische Kommunikationsprotokolle betrachtet.Major innovations and improvements in the automotive industry base on the electronic components. The growing number of functionality in the areas safety, comfort and driver assistance lead to an increase of the complexity. Not only the number of components increase. Especially to realize complex assistance systems the cooperation and data exchange gets more important. In particular, by-wire and assistance systems (highly-automated driving) have high requirements on reliability, data consistency and safety. The cooperation of single control units to realize these complex functions require not only high data rates but also determinism and real-time behavior of the communication architecture. The development of these complex distributed systems benefits from model-based design processes. The verification and validation of system properties with a focus on communication should be possible in early design phases using model and simulation-based approaches based on executable specifications. In this thesis, a modeling approach is developed addressing the typical event-driven and time-triggered protocols in the automotive domain. Models on different abstraction levels are defined and implemented. The Controller Area Network (CAN) and FlexRay are used as examples. Beside the communication protocols some related topics: gateway-functionality (heterogeneous communication) and operating system. The developed detailed models are adequate for the analysis of specific protocol properties as well as the improvement of protocol functions on model level. More abstract models can be used to analyze the performance, real-time behavior and characteristics of large heterogeneous systems. Real-time communication, distributed embedded systems and model-based design processes are not limited to the automotive sector. Therefore the utilization of the modeling approach is demonstrated within the development and optimization of a distributed embedded system: a signal- and dataprocessing unit of a nanopositioning- and nanomeasuringmachine. The example covers most parts of the development process. Selected topics are the design of the system architecture, the distributed allocation of functionality, the realization of single components and the development of application specific communication protocols

CNV-ClinViewer: Enhancing the clinical interpretation of large copy-number variants online

Purpose Large copy number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype-phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts. Methods We developed a web-application combining >250,000 patient and population CNVs together with a large set of biomedical annotations and provide tools for CNV classification based on ACMG/ClinGen guidelines and gene-set enrichment analyses. Results Here, we introduce the CNV-ClinViewer (https://cnv-ClinViewer.broadinstitute.org), an open-source web-application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface. Conclusion Overall, this resource facilitates semi-automated clinical CNV interpretation and genomic loci exploration and, in combination with clinical judgment, enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators patient care and for basic scientists translational genomic research

Cyclic fatigue vs static loading for shear bond strength test of lithium disilicate and dentin substrates: A comparison of resin cement viscosities

Objective: To explore the effect of resin cement viscosities on the shear bond strength under static and fatigue load of lithium disilicate and dentin substrates. Methods: Bonded tri-layer samples (lithium disilicate ceramic cylinder, resin cement, and substrate – ceramic or dentin) was performed considering 2 factors (n = 15): “resin cement viscosity” (high, HV; or low, LV) and “loading mode” (static, s-SBS; or fatigue shear bond strength, f-SBS). The specimens were subjected to s-SBS (1 mm/min, 1 kN load cell) and f-SBS (cyclic fatigue, initial load: 10 N; step-size: 5 N; 10,000 cycles/step; underwater). Failure mode, topography, and finite element analysis (FEA) were performed. Results: The resin cement viscosity did not influence the s-SBS and f-SBS of lithium disilicate substrate; however, it affected the bond strength to dentin, with HV presenting the worst fatigue behavior (f-SBS = 6.89 MPa). Cyclic loading in shear testing induced a notorious detrimental effect with a relevant decrease (16–56 %) in bond strength and survival rates, except for dentin substrate and LV. Most failures were adhesive. A distinct pattern comparing the disilicate and dentin was identified and FEA demonstrated that there was a stress concentration on the top of the cement layer. Significance: Cyclic fatigue loading in shear testing has detrimental effects on the adhesive behavior and survival probabilities of bonded lithium disilicate sets, regardless of resin cement viscosity. In contrast, resin cement viscosity affects the bond strength and the survival rates of dentin substrate submitted to cyclic loading mode, in which a low viscosity results in better performance

Loss of Grin2a causes a transient delay in the electrophysiological maturation of hippocampal parvalbumin interneurons

Abstract N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ionotropic glutamate receptors that mediate a calcium-permeable component to fast excitatory neurotransmission. NMDARs are heterotetrameric assemblies of two obligate GluN1 subunits (GRIN1) and two GluN2 subunits (GRIN2A-GRIN2D). Sequencing data shows that 43% (297/679) of all currently known NMDAR disease-associated genetic variants are within the GRIN2A gene, which encodes the GluN2A subunit. Here, we show that unlike missense GRIN2A variants, individuals affected with disease-associated null GRIN2A variants demonstrate a transient period of seizure susceptibility that begins during infancy and diminishes near adolescence. We show increased circuit excitability and CA1 pyramidal cell output in juvenile mice of both Grin2a +/− and Grin2a −/− mice. These alterations in somatic spiking are not due to global upregulation of most Grin genes (including Grin2b). Deeper evaluation of the developing CA1 circuit led us to uncover age- and Grin2a gene dosing-dependent transient delays in the electrophysiological maturation programs of parvalbumin (PV) interneurons. We report that Grin2a +/+ mice reach PV cell electrophysiological maturation between the neonatal and juvenile neurodevelopmental timepoints, with Grin2a +/− mice not reaching PV cell electrophysiological maturation until preadolescence, and Grin2a −/− mice not reaching PV cell electrophysiological maturation until adulthood. Overall, these data may represent a molecular mechanism describing the transient nature of seizure susceptibility in disease-associated null GRIN2A patients