Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-beta and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.

Over the last twenty years, the open source community has provided more and more software on which the world's High Performance Computing (HPC) systems depend for performance and productivity. The community has invested millions of dollars and years of effort to build key components. But although the investments in these separate software elements have been tremendously valuable, a great deal of productivity has also been lost because of the lack of planning, coordination, and key integration of technologies necessary to make them work together smoothly and efficiently, both within individual PetaScale systems and between different systems. It seems clear that this completely uncoordinated development model will not provide the software needed to support the unprecedented parallelism required for peta/exascale computation on millions of cores, or the flexibility required to exploit new hardware models and features, such as transactional memory, speculative execution, and GPUs. This report describes the work of the community to prepare for the challenges of exascale computing, ultimately combing their efforts in a coordinated International Exascale Software Project.

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One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12‐year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism‐based interventions. These goals will be achieved by: (i) using mobile health (m‐health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real‐life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal‐directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

This paper gives an overview about the Score-P performance measurement infrastructure which is being jointly developed by leading HPC performance tools groups. It motivates the advantages of the joint undertaking from both the developer and the user perspectives, and presents the design and components of the newly developed Score-P performance measurement infrastructure. Furthermore, it contains first evaluation results in comparison with existing performance tools and presents an outlook to the long-term cooperative development of the new system.