DPN -- Dependability Priority Numbers

This paper proposes a novel model-based approach to combine the quantitative dependability (safety, reliability, availability, maintainability and IT security) analysis and trade-off analysis. The proposed approach is called DPN (Dependability Priority Numbers) and allows the comparison of different actual dependability characteristics of a systems with its target values and evaluates them regarding trade-off analysis criteria. Therefore, the target values of system dependability characteristics are taken as requirements, while the actual value of a specific system design are provided by quantitative and qualitative dependability analysis (FHA, FMEA, FMEDA, of CFT-based FTA). The DPN approach evaluates the fulfillment of individual target requirements and perform trade-offs between analysis objectives. We present the workflow and meta-model of the DPN approach, and illustrate our approach using a case study on a brake warning contact system. Hence, we demonstrate how the model-based DPNs improve system dependability by selecting the project crucial dependable design alternatives or measures

Towards Automotive Embedded Systems with Self-X Properties

With self-adaptation and self-organization new paradigms for the management of distributed systems have been introduced. By enhancing the automotive software system with self-X capabilities, e.g. self-healing, self-configuration and self-optimization, the complexity is handled while increasing the flexibility, scalability and dependability of these systems. In this chapter we present an approach for enhancing automotive systems with self-X properties. At first, we discuss the benefits of providing automotive software systems with self-management capabilities and outline concrete use cases. Afterwards, we will discuss requirements and challenges for realizing adaptive automotive embedded systems

Die Rolle der Überexpression von PRMT1 im duktalen Adenokarzinom des Pankreas

Das Ziel dieser Arbeit war die Untersuchung der Rolle von PRMT1 im humanen duktalen Adenokarzinom des Pankreas. Ausgangspunkt hierzu war eine Veröffentlichung, die eine Überexpression von PRMT1 auf Transkriptebene im PDAC relativ zu gesundem Gewebe zeigte. Als erste Aufgabe wurde in der vorliegenden Arbeit der Frage nachgegangen, ob auch eine Erhöhung der Proteinspiegel von PRMT1 im PDAC-Gewebe vorliegt. Durch Vorarbeiten im Labor und im Rahmen dieser Arbeit konnte diese Fragestellung durch immunhistochemische Färbungen von Pankreasschnitten positiv beantwortet werden. Um eine potenzielle Funktion dieser verstärkten PRMT1-Expression im PDAC zu untersuchen, wurde die Proliferationsfähigkeit der PDAC-Zelllinien Panc1 und MiaPaCa2 mittels Wachstumskurven bestimmt. Durch siRNA-vermittelte Depletion von PRMT1 in diesen Zellen wurde deutlich, dass das Protein für die Proliferationsfähigkeit essenziell ist. Diese Erkenntnis ließ sich durch eine Wiederholung des Experiments in HeLa-Zellen auch auf weitere Tumorzellen ausweiten. Zudem wurde die Fähigkeit von PDAC-Zellen zum ankerunabhängigen Wachstum in Soft-Agar-Assays untersucht. Nach Depletion von PRMT1 war diese Fähigkeit gehemmt. In einem weiteren Teil dieser Arbeit wurden zuvor erbrachte Ergebnisse der Arbeitsgruppe bezüglich einer Assoziation des Transkriptionsfaktors GLI1 mit PRMT1 einer Validierung und weiteren Bearbeitung unterzogen. Mit Hilfe von Expressionsanalysen auf Transkriptebene konnten keine belastbaren Hinweise auf einen Einfluss von PRMT1 auf die GLI1-Spiegel festgestellt werden. Eine Interaktion der beiden Proteine konnte weder in vivo noch in vitro nachgewiesen werden und eine Methylierung von GLI1 durch PRMT1 konnte nicht abschließend verifiziert werden. Eine Rolle von PRMT1 bei der Koaktivierung der GLI1-abhängigen Genexpression bleibt fraglich und bedarf weiterer Untersuchungen. Dem Transkriptionsfaktor c-MYC wurde in Veröffentlichungen eine steigernde Wirkung auf die Expressionsrate von PRMT1 im Zuge von Entwicklungsprozessen nachgewiesen. In der vorliegenden Arbeit wurde geprüft, ob dieser Mechanismus auch in Zellen des PDAC existiert. Mit Hilfe von c-MYC-Depletionen konnte bestätigt werden, dass in diesem System ebenfalls eine Regulation der Expression von PRMT1 durch c-MYC sowohl auf Transkript- als auch auf Proteinebene stattfindet. Durch Hybridisierung eines Oligonukleotid-Microarrays wurde der Einfluss von PRMT1 auf das Transkriptom von Panc1-PDAC-Zellen analysiert. Von den 51 erhaltenen Kandidatengenen, die unter siRNA-vermittelter PRMT1-Depletion mehr als zweifach in ihrer Expression reguliert waren, konnten bisher zwei Gene validiert werden. Für die Proteine GLIPR1 und ANXA8, die von diesen Genen kodiert werden, wurden in verschiedenen Publikationen bereits tumorrelevante Funktionen nachgewiesen. Die weitere funktionelle Charakterisierung dieser Proteine im PDAC wird eine der Aufgaben im künftigen Verlauf des Projekts sein

Automatic Generation of RAMS Analyses from Model-based Functional Descriptions using UML State Machines

In today's industrial practice, safety, reliability or availability artifacts such as fault trees, Markov models or FMEAs are mainly created manually by experts, often distinctively decoupled from systems engineering activities. Significant efforts, costs and timely requirements are involved to conduct the required analyses. In this paper, we describe a novel integrated model-based approach of systems engineering and dependability analyses. The behavior of system components is specified by UML state machines determining intended/correct and undesired/faulty behavior. Based on this information, our approach automatically generates different dependability analyses in the form of fault trees. Hence, alternative system layouts can easily be evaluated. The same applies for simple variations of the logical input-output relations of logical units such as controllers. We illustrate the feasibility of our approach with the help of simple examples using a prototypical implementation of the presented concepts

Ensuring referential integrity under causal consistency

Referential integrity (RI) is an important correctness property of a shared, distributed object storage system. It is sometimes thought that enforcing RI requires a strong form of consistency. In this paper, we argue that causal consistency suffices to maintain RI. We support this argument with pseudocode for a reference CRDT data type that maintains RI under causal consistency. QuickCheck has not found any errors in the model

Towards a safe MLOps Process for the Continuous Development and Safety Assurance of ML-based Systems in the Railway Domain

Traditional automation technologies alone are not sufficient to enable driverless operation of trains (called Grade of Automation (GoA) 4) on non-restricted infrastructure. The required perception tasks are nowadays realized using Machine Learning (ML) and thus need to be developed and deployed reliably and efficiently. One important aspect to achieve this is to use an MLOps process for tackling improved reproducibility, traceability, collaboration, and continuous adaptation of a driverless operation to changing conditions. MLOps mixes ML application development and operation (Ops) and enables high frequency software releases and continuous innovation based on the feedback from operations. In this paper, we outline a safe MLOps process for the continuous development and safety assurance of ML-based systems in the railway domain. It integrates system engineering, safety assurance, and the ML life-cycle in a comprehensive workflow. We present the individual stages of the process and their interactions. Moreover, we describe relevant challenges to automate the different stages of the safe MLOps process

Automatized online prediction of slow-wave peaks during non-rapid eye movement sleep in young and old individuals: Why we should not always rely on amplitude thresholds.

Brain-state-dependent stimulation during slow-wave sleep is a promising tool for the treatment of psychiatric and neurodegenerative diseases. A widely used slow-wave prediction algorithm required for brain-state-dependent stimulation is based on a specific amplitude threshold in the electroencephalogram. However, due to decreased slow-wave amplitudes in aging and psychiatric conditions, this approach might miss many slow-waves because they do not fulfill the amplitude criterion. Here, we compared slow-wave peaks predicted via an amplitude-based versus a multidimensional approach using a topographical template of slow-wave peaks in 21 young and 21 older healthy adults. We validate predictions against the gold-standard of offline detected peaks. Multidimensionally predicted peaks resemble the gold-standard regarding spatiotemporal dynamics but exhibit lower peak amplitudes. Amplitude-based prediction, by contrast, is less sensitive, less precise and - especially in the older group - predicts peaks that differ from the gold-standard regarding spatiotemporal dynamics. Our results suggest that amplitude-based slow-wave peak prediction might not always be the ideal choice. This is particularly the case in populations with reduced slow-wave amplitudes, like older adults or psychiatric patients. We recommend the use of multidimensional prediction, especially in studies targeted at populations other than young and healthy individuals

Diffuse fibromuscular dysplasia successfully treated with scoring balloon angioplasty in a 3-year-old boy

In children, up to 10% of the cases of arterial hypertension may be caused by a renovascular disease. The etiology of this renovascular disease is most of the time due to a fibromuscular dysplasia (FMD), which causes a noninflammatory intimal-medial fibroplasia leading to luminal compromise. Percutaneous transluminal angioplasty of FMD is a worldwide-accepted treatment modality for this serious arterial disease with, so far, good safety and long-term efficacy data. Once FMD involves several arterial compartments leading to symptoms the outcomes are poor. Herein we report the case of a 3½-year-old boy with severe arterial hypertension and abdominal angina due to a diffuse multivisceral FMD involvement, successfully managed by a percutaneous angioplasty approach using a new balloon catheter for plaque modulatio

Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium : case-control study

Objective : To evaluate the effectiveness of rotavirus vaccination among young children in Belgium. Design : Prospective case-control study. Setting : Random sample of 39 Belgian hospitals, February 2008 to June 2010. Participants : 215 children admitted to hospital with rotavirus gastroenteritis confirmed by polymerase chain reaction and 276 age and hospital matched controls. All children were of an eligible age to have received rotavirus vaccination (that is, born after 1 October 2006 and aged >= 14 weeks). Main outcome measure : Vaccination status of children admitted to hospital with rotavirus gastroenteritis and matched controls. Results : 99 children (48%) admitted with rotavirus gastroenteritis and 244 (91%) controls had received at least one dose of any rotavirus vaccine (P= 12 months. The G2P[4] genotype accounted for 52% of cases confirmed by polymerase chain reaction with eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by polymerase chain reaction with eligible matched controls, there was reported co-infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness against co-infected cases was 86% (52% to 96%). Effectiveness of at least one dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to 95%). Conclusions : Rotavirus vaccination is effective for the prevention of admission to hospital for rotavirus gastroenteritis among young children in Belgium, despite the high prevalence of G2P[4] and viral co-infection