Virtualisierung eingebetteter Echtzeitsysteme im Mehrkernbetrieb zur Partitionierung sicherheitsrelevanter Fahrzeugsoftware

Die Automobilindustrie verzeichnete innerhalb der letzten Jahre einen enormen Zuwachs an neuen elektrischen und elektronischen Fahrzeugfunktionen. Dies führt gleichzeitig zu einer Mehrung der Softwareumfänge in eingebetteten Systemen. Nicht-funktionale Anforderungen wie Sicherheit, Performanz, Verlässlichkeit und Wartbarkeit stellen zusätzliche Herausforderungen an die Entwicklung zukünftiger Fahrzeugsysteme dar. Um die Anzahl der Steuergeräte zu reduzieren, sollen Fahrzeugfunktionen auf gemeinsamen Integrationssteuergeräten konsolidiert werden. Systemvirtualisierung kann hierfür eine zielführende Herangehensweise darstellen, um die Softwaremigration auf Integrationssteuergeräte zu erleichtern und gleichzeitig den geforderten Isolationsansprüchen neuer Sicherheitsstandards gerecht zu werden. In dieser Arbeit wird die Partitionierung sicherheitsrelevanter Fahrzeugfunktionen auf einer gemeinsamen Hardwareplattform fokussiert. Unter Verwendung von Methoden zur Bewertung sozialer Netzwerke wird eine graphenbasierte Herangehensweise vorgestellt, um die Partitionierbarkeit von Softwarenetzen mit sicherheitsrelevanten Anteilen abschätzen zu können. Zur Realisierung der Systempartitionierung wird eine Methodik zur Auswahl der geeignetsten Kernelarchitektur eingeführt. Dabei werden aus gewählten nicht-funktionalen Eigenschaften potentielle technische Lösungskonzepte innerhalb einer Baumstruktur abgeleitet und ingenieurmäßig bewertet. Darauf aufbauend wird ein Hypervisor für eingebettete Echtzeitsysteme der Firma ETAS Ltd. evaluiert. Um die Kosten einer zusätzlichen Hypervisorschicht beurteilen zu können, werden in diesem Rahmen Laufzeitmessungen durchgeführt. Somit werden die Auswirkungen einer zusätzlichen Virtualisierungsschicht auf Fahrzeugsoftwaresysteme zur Erfüllung ausgewählter nicht-funktionaler Eigenschaften aufgezeigt. Die Anbindung virtualisierter Systeme an die Kommunikationsschnittstellen des Hypervisors stellt einen weiteren Schwerpunkt dar. Virtuelle Steuergeräte tauschen sich weiterhin über bereits implementierte Kommunikationskanäle aus und greifen auf gemeinsame Hardwareressourcen zu. Es wird somit ein Konzept eingeführt, um sicherheitsrelevante Anteile des AUTOSAR Microcontroller Abstraction Layers zu entkoppeln. Der Hypervisor selbst wird hierzu an relevanten Stellen erweitert und ein verlässliches Kommunikationskonzept implementiert. Ein Demonstratoraufbau, zur Konsolidierung von produktiver Fahrzeugsoftware auf einer gemeinsamen Hardwareplattform, finalisiert die Arbeit. Hierfür werden unabhängige Softwarestände paravirtualisiert. Als Resümee der Arbeit erhält der Leser sowohl einen technischen Überblick über den Mehrwert als auch der Kosten paravirtualisierter Fahrzeugplattformen, welche auf Kleinststeuergeräten integriert sind.Within the automotive industry, electric and electronic functionality is rapidly rising within the last few years. This fact yields an increase of software functionality of embedded systems within the car. Non-functional requirements like safety, performance, reliability or maintainability represent additional challenges for future vehicle system development. Vehicle functionality is consolidated on common hardware platforms, to reduce the amount of electronic control units. System virtualization can act as a proper approach, to ease the migration of different vehicle applications to a consolidated system and achieve additional demands for functional isolation. Within this thesis, the partitioning of safety-related automotive applications on a common hardware platform is focused. To assess the partitioning of safety-related automotive systems, methods for social network evaluation with a graph-oriented approach are proposed. For realizing the system partitioning, a decision-making model is introduced, which results in the most appropriate kernel architecture. From a chosen set of non-functional requirements, technical solutions are derived and rated from a tree structure. As a result, a hypervisor for embedded real-time systems, supplied by ETAS Ltd., is evaluated. For that purpose, timing measurements are performed to estimate the costs of virtual electronic control units. The impact of an additional virtualization layer for automotive software systems to achieve non-functional requirements is analyzed. A further main focus is the integration of virtualized systems to the communication interfaces of the hypervisor. Virtual ECUs further exchange information over already implemented communication channels and use common hardware ressources. Thus, a concept to decouple the safety-related parts of the AUTOSAR Microcontroller Abstraction Layer is introduced. The hypervisor itself will be enhanced by a reliable communication concept. A demonstrator to consolidate already productive automotive applications on a common hardware platform finalizes the work. Here, independent software parts are paravirtualized. This thesis concludes with a technical overview of the benefits and costs for integrating paravirtualized electronic control units on less capable hardware platforms

Phyllotaxis involves auxin drainage through leaf primordia

The spatial arrangement of leaves and flowers around the stem, known as phyllotaxis, is controlled by an auxin-dependent reiterative mechanism that leads to regular spacing of the organs and thereby to remarkably precise phyllotactic patterns. The mechanism is based on the active cellular transport of the phytohormone auxin by cellular influx and efflux carriers, such as AUX1 and PIN1. Their important role in phyllotaxis is evident from mutant phenotypes, but their exact roles in space and time are difficult to address due to the strong pleiotropic phenotypes of most mutants in phyllotaxis. Models of phyllotaxis invoke the accumulation of auxin at leaf initials and removal of auxin through their developing vascular strand, the midvein. We have developed a precise microsurgical tool to ablate the midvein at high spatial and temporal resolution in order to test its function in leaf formation and phyllotaxis. Using amplified femtosecond laser pulses, we ablated the internal tissues in young leaf primordia of tomato (Solanum lycopersicum) without damaging the overlying L1 and L2 layers. Our results show that ablation of the future midvein leads to a transient accumulation of auxin in the primordia and to an increase in their width. Phyllotaxis was transiently affected after midvein ablations, but readjusted after two plastochrons. These results indicate that the developing midvein is involved in the basipetal transport of auxin through young primordia, which contributes to phyllotactic spacing and stability

Геофизические закономерности локализации месторождений углеводородов Баренцево-Карского региона

Background: Rising serum levels of prostate-specific antigen (PSA) after radical prostatectomy are indicative of recurrent prostate cancer. This double-blind, placebo-controlled phase II study evaluated the anti-tumour activity of the anti-epithelial cell adhesion molecule (EpCAM) antibody adecatumumab in delaying biochemical disease progression. Patients and Methods: Prostate cancer patients with increasing serum PSA levels following radical prostatectomy were randomized to low- (2 mg/kg) or high-dose adecatumumab (6 mg/kg) or placebo. The primary efficacy endpoint was the mean change from baseline in total serum PSA at week 24. Secondary endpoints included PSA response rate, prolongation of serum PSA doubling time and time to biochemical disease progression. Results: The primary and secondary endpoints of the study were not met in the predefined analyses. In a retrospective analysis of patients with baseline PSA <= 1 ng/ml and a high EpCAM expression, both the mean increase in PSA from baseline to week 24 and the PSA doubling time at week 15 were significantly improved in the high-dose adecatumumab group compared with the placebo group. Most frequent treatment-related clinical adverse events were gastrointestinal (diarrhoea and nausea) or general events (chills), showing a dose dependency but no grade 3/4 intensity in any patient. Conclusion: In men with rising PSA levels after radical prostatectomy and no evidence of clinical relapse, adecatumumab delayed disease progression in a subgroup of patients with baseline PSA levels <= 1 ng/ml and high EpCAM-expressing tumours. Copyright (C) 2010 S. Karger AG, Base

Cardiovascular mortality and exposure to extremely low frequency magnetic fields: a cohort study of Swiss railway workers

<p>Abstract</p> <p>Background</p> <p>Exposure to intermittent magnetic fields of 16 Hz has been shown to reduce heart rate variability, and decreased heart rate variability predicts cardiovascular mortality. We examined mortality from cardiovascular causes in railway workers exposed to varying degrees to intermittent 16.7 Hz magnetic fields.</p> <p>Methods</p> <p>We studied a cohort of 20,141 Swiss railway employees between 1972 and 2002, including highly exposed train drivers (median lifetime exposure 120.5 μT-years), and less or little exposed shunting yard engineers (42.1 μT-years), train attendants (13.3 μT-years) and station masters (5.7 μT-years). During 464,129 person-years of follow up, 5,413 deaths were recorded and 3,594 deaths were attributed to cardio-vascular diseases. We analyzed data using Cox proportional hazards models.</p> <p>Results</p> <p>For all cardiovascular mortality the hazard ratio compared to station masters was 0.99 (95%CI: 0.91, 1.08) in train drivers, 1.13 (95%CI: 0.98, 1.30) in shunting yard engineers, and 1.09 (95%CI: 1.00, 1.19) in train attendants.Corresponding hazard ratios for arrhythmia related deaths were 1.04 (95%CI: 0.68, 1.59), 0.58 (95%CI: 0.24, 1.37) and 1.30 (95%CI: 0.87, 1.93) and for acute myocardial infarction 1.00 (95%CI: 0.73, 1.36), 1.56 (95%CI: 1.04, 2.32), and 1.14 (95%CI: 0.85, 1.53). The hazard ratio for arrhythmia related deaths per 100 μT-years of cumulative exposure was 0.94 (95%CI: 0.71, 1.24) and 0.91 (95%CI: 0.75, 1.11) for acute myocardial infarction.</p> <p>Conclusion</p> <p>This study provides evidence against an association between long-term occupational exposure to intermittent 16.7 Hz magnetic fields and cardiovascular mortality.</p

Aerosolized BC-819 Inhibits Primary but Not Secondary Lung Cancer Growth

Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819

Expression of ECM proteins fibulin-1 and -2 in acute and chronic liver disease and in cultured rat liver cells

Fibulin-2 has previously been considered as a marker to distinguish rat liver myofibroblasts from hepatic stellate cells. The function of other fibulins in acute or chronic liver damage has not yet been investigated. The aim of this study has been to evaluate the expression of fibulin-1 and -2 in models of rat liver injury and in human liver cirrhosis. Their cellular sources have also been investigated. In normal rat liver, fibulin-1 and -2 were both mainly present in the portal field. Fibulin-1-coding transcripts were detected in total RNA of normal rat liver, whereas fibulin-2 mRNA was only detected by sensitive, real-time quantitative polymerase chain reaction. In acute liver injury, the expression of fibulin-1 was significantly increased (17.23-fold after 48 h), whereas that of fibulin-2 was not modified. The expression of both fibulin-1 and -2 was increased in experimental rat liver cirrhosis (19.16- and 26.47-fold, respectively). At the cellular level, fibulin-1 was detectable in hepatocytes, “activated” hepatic stellate cells, and liver myofibroblasts (2.71-, 122.65-, and 469.48-fold over the expression in normal rat liver), whereas fibulin-2 was restricted to liver myofibroblasts and was regulated by transforming growth factor beta-1 (TGF-β1) in 2-day-old hepatocyte cultures and in liver myofibroblasts. Thus, fibulin-1 and -2 respond differentially to single and repeated damaging noxae, and their expression is differently present in liver cells. Expression of the fibulin-2 gene is regulated by TGF-β1 in liver myofibroblasts

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications