Modular Architecture and Unique Teichoic Acid Recognition Features of Choline-Binding Protein L (CbpL) Contributing to Pneumococcal Pathogenesis

The human pathogen Streptococcus pneumoniae is decorated with a special class of surface-proteins known as choline-binding proteins (CBPs) attached to phosphorylcholine (PCho) moieties from cell-wall teichoic acids. By a combination of X-ray crystallography, NMR, molecular dynamics techniques and in vivo virulence and phagocytosis studies, we provide structural information of choline-binding protein L (CbpL) and demonstrate its impact on pneumococcal pathogenesis and immune evasion. CbpL is a very elongated three-module protein composed of (i) an Excalibur Ca 2+ -binding domain -reported in this work for the very first time-, (ii) an unprecedented anchorage module showing alternate disposition of canonical and non-canonical choline-binding sites that allows vine-like binding of fully-PCho-substituted teichoic acids (with two choline moieties per unit), and (iii) a Ltp-Lipoprotein domain. Our structural and infection assays indicate an important role of the whole multimodular protein allowing both to locate CbpL at specific places on the cell wall and to interact with host components in order to facilitate pneumococcal lung infection and transmigration from nasopharynx to the lungs and blood. CbpL implication in both resistance against killing by phagocytes and pneumococcal pathogenesis further postulate this surface-protein as relevant among the pathogenic arsenal of the pneumococcus.We gratefully acknowledge Karsta Barnekow and Kristine Sievert-Giermann, for technical assistance and Lothar Petruschka for in silico analysis (all Dept. of Genetics, University of Greifswald). We are further grateful to the staff from SLS synchrotron beamline for help in data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft DFG GRK 1870 (to SH) and the Spanish Ministry of Economy and Competitiveness (BFU2014-59389-P to JAH, CTQ2014-52633-P to MB and SAF2012-39760-C02-02 to FG) and S2010/BMD- 2457 (Community of Madrid to JAH and FG).Peer Reviewe

A Quantitative Approach to Architecting All-Flash Lustre File Systems

New experimental and AI-driven workloads are moving into the realm of extreme-scale HPC systems at the same time that high-performance flash is becoming cost-effective to deploy at scale. This confluence poses a number of new technical and economic challenges and opportunities in designing the next generation of HPC storage and I/O subsystems to achieve the right balance of bandwidth, latency, endurance, and cost. In this work, we present quantitative models that use workload data from existing, disk-based file systems to project the architectural requirements of all-flash Lustre file systems. Using data from NERSC’s Cori I/O subsystem, we then demonstrate the minimum required capacity for data, capacity for metadata and data-on-MDT, and SSD endurance for a future all-flash Lustre file system

Towards Participatory E-Government?: Learning from E-Government Project Evaluations

Part 4: Critical ReflectionsInternational audienceThe question is whether citizens are sufficiently involved in the development of the facilities used to support e-Government, so they can safeguard the quality of these facilities. It is a relevant issue, as the projects in which these facilities are created often provide insufficient functionality. Based on a sample test, we selected evaluation reports of such projects and studied them based on a perceptual framework. It turns out that e-Government projects have been poorly evaluated and thereby governed. The evaluation governance instruments did not include any participative role of stakeholders. Principles of modern public administration theories are not sufficiently visible within the government in this regard. The quality can be improved substantially by involving representatives of industry and professional organizations, and by introducing co-creation before, during and after completion of projects, as well as during the corresponding evaluations and reflections