Communication Centric Design in Complex Automotive Embedded Systems

Automotive embedded applications like the engine management system are composed of multiple functional components that are tightly coupled via numerous communication dependencies and intensive data sharing, while also having real-time requirements. In order to cope with complexity, especially in multi-core settings, various communication mechanisms are used to ensure data consistency and temporal determinism along functional cause-effect chains. However, existing timing analysis methods generally only support very basic communication models that need to be extended to handle the analysis of industry grade problems which involve more complex communication semantics. In this work, we give an overview of communication semantics used in the automotive industry and the different constraints to be considered in the design process. We also propose a method for model transformation to increase the expressiveness of current timing analysis methods enabling them to work with more complex communication semantics. We demonstrate this transformation approach for concrete implementations of two communication semantics, namely, implicit and LET communication. We discuss the impact on end-to-end latencies and communication overheads based on a full blown engine management system

Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice

<p>Abstract</p> <p>Background</p> <p>In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation, and alleviated cognitive deficits. Furthermore, ADAM10 overexpression increased the cortical synaptogenesis. These results suggest that upregulation of ADAM10 in the brain has beneficial effects on AD pathology.</p> <p>Results</p> <p>To assess the influence of ADAM10 on the gene expression profile in the brain, we performed a microarray analysis using RNA isolated from brains of five months old mice overexpressing either the α-secretase ADAM10, or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, in ADAM10 transgenic mice 355 genes, and in dnADAM10 mice 143 genes were found to be differentially expressed. A higher number of genes was differentially regulated in double-transgenic mouse strains additionally expressing the human APP_[V717I]mutant.</p> <p>Overexpression of proteolytically active ADAM10 affected several physiological pathways, such as cell communication, nervous system development, neuron projection as well as synaptic transmission. Although ADAM10 has been implicated in Notch and β-catenin signaling, no significant changes in the respective target genes were observed in adult ADAM10 transgenic mice.</p> <p>Real-time RT-PCR confirmed a downregulation of genes coding for the inflammation-associated proteins S100a8 and S100a9 induced by moderate ADAM10 overexpression. Overexpression of the dominant-negative form dnADAM10 led to a significant increase in the expression of the fatty acid-binding protein Fabp7, which also has been found in higher amounts in brains of Down syndrome patients.</p> <p>Conclusion</p> <p>In general, there was only a moderate alteration of gene expression in ADAM10 overexpressing mice. Genes coding for pro-inflammatory or pro-apoptotic proteins were not over-represented among differentially regulated genes. Even a decrease of inflammation markers was observed. These results are further supportive for the strategy to treat AD by increasing the α-secretase activity.</p

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion

A systems medicine research approach for studying alcohol addiction

According to the World Health Organization, about 2 billion people drink alcohol. Excessive alcohol consumption can result in alcohol addiction, which is one of the most prevalent neuropsychiatric diseases afflicting our society today. Prevention and intervention of alcohol binging in adolescents and treatment of alcoholism are major unmet challenges affecting our health-care system and society alike. Our newly formed German SysMedAlcoholism consortium is using a new systems medicine approach and intends (1) to define individual neurobehavioral risk profiles in adolescents that are predictive of alcohol use disorders later in life and (2) to identify new pharmacological targets and molecules for the treatment of alcoholism. To achieve these goals, we will use omics-information from epigenomics, genetics transcriptomics, neurodynamics, global neurochemical connectomes and neuroimaging (IMAGEN; Schumann et al. ) to feed mathematical prediction modules provided by two Bernstein Centers for Computational Neurosciences (Berlin and Heidelberg/Mannheim), the results of which will subsequently be functionally validated in independent clinical samples and appropriate animal models. This approach will lead to new early intervention strategies and identify innovative molecules for relapse prevention that will be tested in experimental human studies. This research program will ultimately help in consolidating addiction research clusters in Germany that can effectively conduct large clinical trials, implement early intervention strategies and impact political and healthcare decision makers

The Impact of Adolescent Binge Drinking and Sustained Abstinence on Affective State

BACKGROUND: While it is clear that affect is negatively impacted by heavy drinking in adulthood and that it improves with abstinence, little is known about effects of heavy drinking on mood during adolescence. METHODS: The present study examined negative mood states among 16–18 year-old high school students with a history of recent heavy episodic drinking (HED; n = 39) and comparison youth with limited lifetime drinking experience (CON; n = 26). Affect was assessed at three time points during a 4–6 week period of monitored abstinence using the Hamilton Rating Scales for Anxiety and Depression; self-reports were obtained with the state portion of the State Trait Anxiety Inventory, and experience sampling of current affect was assessed via daily text messages sent at randomly determined times in the morning, afternoon, and evening. RESULTS: Youth with a recent history of HED reported more negative affect compared to non-drinking youth during early stages of abstinence (days since last HED at assessment 1: m = 6.46; SD = 5.06); however differences in affect were not observed after 4–6 weeks of abstinence. Sex differences were evident, with HED girls reporting greater depression and anxiety than HED male peers. Although not significant, response patterns indicated that males may experience faster resolution of negative emotional states than females with sustained abstinence. CONCLUSIONS: Findings suggest that high dose drinking is associated with elevated negative affect for adolescents and that negative mood states may take longer to resolve for girls than for boys following heavy drinking episodes. Future research clarifying naturally occurring changes in affective response during early and sustained abstinence is necessary for improving programs designed to promote adolescent decision-making and to reduce risk for relapse

Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module