Developing Automotive Products Using the EAST-ADL2, an AUTOSAR Compliant Architecture Description Language

International audienceCurrent development trends in automotive software feature increasing standardization of the embedded software structure. But it still remains the critical issue of the overall engineering information management to control the system definition and manage its complexity. System modeling based onan Architecture Description Language (ADL) is a way to keep these assets within one information structure. The original EAST-ADL was developed in the EAST-EEA project (www.east-eea.org) and basic concepts were reused in the AUTOSAR standardization initiative. The original EAST-ADL is currently refined in the ATESST project (www.atesst.org) to EAST-ADL2. This paper presents the results of the language extension provided by the EAST-ADL2 domain model and focuses on its possible extension of the AUTOSAR standard to support decomposition of E/E automotive systems

Delphi Study to Reach International Consensus Among Vascular Surgeons on Major Arterial Vascular Surgical Complications

Background: The complications discussed with patients by surgeons prior to surgery vary, because no consensus on major complications exists. Such consensus may improve informed consent and shared decision-making. This study aimed to achieve consensus among vascular surgeons on which complications are considered ‘major’ and which ‘minor,’ following surgery for abdominal aortic aneurysm (AAA), carotid artery disease (CAD) and peripheral artery disease (PAD). Methods: Complications following vascular surgery were extracted from Cochrane reviews, national guidelines, and reporting standards. Vascular surgeons from Europe and North America rated complications as major or minor on five-point Likert scales via an electronic Delphi method. Consensus was reached if ≥ 80% of participants scored 1 or 2 (minor) or 4 or 5 (major). Results: Participants reached consensus on 9–12 major and 6–10 minor complications per disease. Myocardial infarction, stroke, renal failure and allergic reactions were considered to be major complications of all three diseases. All other major complications were treatment specific or dependent on disease severity, e.g., spinal cord ischemia, rupture following AAA repair, stroke for CAD or deep wound infection for PAD. Conclusion: Vascular surgeons reached international consensus on major and minor complications following AAA, CAD and PAD treatment. This consensus may be helpful in harmonizing the information patients receive and improving standardization of the informed consent procedure. Since major complications differed between diseases, consensus on disease-specific complications to be discussed with patients is necessary

Gas phase formation of extremely oxidized pinene reaction products in chamber and ambient air

High molecular weight (300–650 Da) naturally charged negative ions have previously been observed at a boreal forest site in Hyytiälä, Finland. The long-term measurements conducted in this work showed that these ions are observed practically every night between spring and autumn in Hyytiälä. The ambient mass spectral patterns could be reproduced in striking detail during additional measurements of α-pinene (C<sub>10</sub>H<sub>16</sub>) oxidation at low-OH conditions in the Jülich Plant Atmosphere Chamber (JPAC). The ions were identified as clusters of the nitrate ion (NO<sub>3</sub><sup>−</sup>) and α-pinene oxidation products reaching oxygen to carbon ratios of 0.7–1.3, while retaining most of the initial ten carbon atoms. Attributing the ions to clusters instead of single molecules was based on additional observations of the same extremely oxidized organics in clusters with HSO<sub>4</sub><sup>−</sup> (Hyytiälä) and C<sub>3</sub>F<sub>5</sub>O<sub>2</sub><sup>−</sup> (JPAC). The most abundant products in the ion spectra were identified as C<sub>10</sub>H<sub>14</sub>O<sub>7</sub>, C<sub>10</sub>H<sub>14</sub>O<sub>9</sub>, C<sub>10</sub>H<sub>16</sub>O<sub>9</sub>, and C<sub>10</sub>H<sub>14</sub>O<sub>11</sub>. The mechanism responsible for forming these molecules is still not clear, but the initial reaction is most likely ozone attack at the double bond, as the ions are mainly observed under dark conditions. β-pinene also formed highly oxidized products under the same conditions, but less efficiently, and mainly C<sub>9</sub> compounds which were not observed in Hyytiälä, where β-pinene on average is 4–5 times less abundant than α-pinene. Further, to explain the high O/C together with the relatively high H/C, we propose that geminal diols and/or hydroperoxide groups may be important. We estimate that the night-time concentration of the sum of the neutral extremely oxidized products is on the order of 0.1–1 ppt (~10<sup>6</sup>–10<sup>7</sup> molec cm<sup>−3</sup>). This is in a similar range as the amount of gaseous H<sub>2</sub>SO<sub>4</sub> in Hyytiälä during day-time. As these highly oxidized organics are roughly 3 times heavier, likely with extremely low vapor pressures, their role in the initial steps of new aerosol particle formation and growth may be important and needs to be explored in more detail in the future

Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT

Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFß-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFß pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFß-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFß-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFß-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFß stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads

A Qualitative Comparison of Approaches Supporting Business Process Variability

The increasing adoption of process-aware information systems, together with the reuse of process knowledge, has led to the emergence of process model repositories with large process families, i.e., collections of related process model variants. For managing such related model collections two types of approaches exist. While behavioral approaches take supersets of variants and derive a process variant by hiding and blocking process elements, structural approaches take a base process model as input and derive a process variant by applying a set of change operations to it. However, at the current stage no framework for assessing these approaches exists and it is not yet clear which approach should be better used and under which circumstances. Therefore, to give first insights about this issue, this work compares both approaches in terms of understandability of the produced process model artifacts, which is fundamental for the management of process families and the reuse of their contained process fragments. In addition, the comparison can serve as theoretical basis for conducting experiments as well as for fostering the development of tools managing business process variability

A case–control study of risk of leukaemia in relation to mobile phone use

Background Mobile phone use is now ubiquitous, and scientific reviews have recommended research into its relation to leukaemia risk, but no large studies have been conducted.Methods In a case-control study in South East England to investigate the relation of acute and non-lymphocytic leukaemia risk to mobile phone use, 806 cases with leukaemia incident 2003-2009 at ages 18-59 years (50% of those identified as eligible) and 585 non-blood relatives as controls (provided by 392 cases) were interviewed about mobile phone use and other potentially aetiological variables.Results No association was found between regular mobile phone use and risk of leukaemia (odds ratio (OR)=1.06, 95% confidence interval (CI)=0.76, 1.46). Analyses of risk in relation to years since first use, lifetime years of use, cumulative number of calls and cumulative hours of use produced no significantly raised risks, and there was no evidence of any trends. A non-significantly raised risk was found in people who first used a phone 15 or more years ago (OR=1.87, 95% CI=0.96, 3.63). Separate analyses of analogue and digital phone use and leukaemia subtype produced similar results to those overall.Conclusion This study suggests that use of mobile phones does not increase leukaemia risk, although the possibility of an effect after long-term use, while biologically unlikely, remains open