Evidence for somatic selection of natural autoantibodies.

Natural autoantibodies are primarily immunoglobulin M (IgM) antibodies that bind to a variety of self-antigens, including self-IgG. Accounting for a large proportion of the early B cell repertoire, such polyspecific autoantibodies are speculated to contribute to the homeostasis and/or competence of the primary humoral immune system. Recent studies indicate that the leukemia cells from most patients with chronic lymphocytic leukemia (CLL) also express such IgM autoantibodies. Similarly, the leukemia cells from many CLL patients react with murine monoclonal antibodies (mAbs) specific for crossreactive idiotypes (CRIs) associated with human IgM autoantibodies. In particular, leukemic cells frequently react with G6, a mAb specific for an Ig heavy chain (H chain)-associated CRI, and/or with 17.109, a mAb that defines a kappa light chain (L chain)-associated CRI. Generated against IgM rheumatoid factor (RF) paraproteins, G6 and 17.109 each recognize a major CRI that is present in many IgM RF paraproteins. Furthermore, over 90% of the IgM paraproteins found to bear both H and L chain-associated CRIs also are found to have RF activity. Molecular characterization of these CRIs demonstrates that each is a serologic marker for expression of a highly conserved Ig V gene. As such, the frequent production of IgM polyspecific autoantibodies in CLL simply may reflect the frequent use of such highly conserved autoantibody-encoding Ig V genes with little or no somatic mutation. To test this hypothesis, we generated murine transfectomas to pair the 17.109-reactive kappa L chain of SMI, a 17.109/G6-reactive CLL population, with the Ig H chain of SMI or other G6-reactive leukemia cells or tonsillar lymphocytes. Cotransfection of vectors encoding the Ig H and L chains of SMI generated transfectomas that produce IgM kappa RF autoantibodies reactive with human IgG1 and IgG4. In contrast to G6/17.109-reactive IgM kappa RF Waldenstrom's paraproteins, the SMI IgM kappa also reacts with several other self-antigens, including myoglobin, actin, and ssDNA. However, cotransfection of the SMI L chain with a vector encoding any one of 10 different G6-reactive Ig H chains generated transfectomas that produce IgM kappa antibodies without detectable polyspecific autoantibody activity. These results indicate that polyspecific antiself-reactivity of G6/17.019-reactive Ig is dependent on the somatically generated Ig third complementarity determining region. Collectively, these studies imply that selection may be responsible for the frequent expression of polyspecific autoantibodies in CLL and early B cell ontogeny

Assisted assignment of automotive safety requirements

ISO 26262, a functional-safety standard, uses Automotive Safety Integrity Levels (ASILs) to assign safety requirements to automotive-system elements. System designers initially assign ASILs to system-level hazards and then allocate them to elements of the refined system architecture. Through ASIL decomposition, designers can divide a function & rsquo;s safety requirements among multiple components. However, in practice, manual ASIL decomposition is difficult and produces varying results. To overcome this problem, a new tool automates ASIL allocation and decomposition. It supports the system and software engineering life cycle by enabling users to efficiently allocate safety requirements regarding systematic failures in the design of critical embedded computer systems. The tool is applicable to industries with a similar concept of safety integrity levels. © 1984-2012 IEEE

A batch scheduler with high level components

In this article we present the design choices and the evaluation of a batch scheduler for large clusters, named OAR. This batch scheduler is based upon an original design that emphasizes on low software complexity by using high level tools. The global architecture is built upon the scripting language Perl and the relational database engine Mysql. The goal of the project OAR is to prove that it is possible today to build a complex system for ressource management using such tools without sacrificing efficiency and scalability. Currently, our system offers most of the important features implemented by other batch schedulers such as priority scheduling (by queues), reservations, backfilling and some global computing support. Despite the use of high level tools, our experiments show that our system has performances close to other systems. Furthermore, OAR is currently exploited for the management of 700 nodes (a metropolitan GRID) and has shown good efficiency and robustness

An assessment of environmental impacts of cassava starch extraction technologies

The environmental impacts of the transformation of cassava roots into starch were assessed for three contrasting technologies at small and large scale (1-2 and 100-200t starch per day), using the Life Cycle Assessment (LCA) methodology. The objective was to assess impacts for each unit operation, so as to identify impacts hotspots as well as sustainable practices, with a view to uncover opportunities for improving the environmental performance of cassava starch production. The system boundaries were defined as the unit operations used to transform fresh cassava roots delivered at factory gate into loose, dry cassava starch. Inventory data indicated wide variations in energy and water consumption. The large scale technology required 702kWh/t starch, mainly (75%) from fuel oil used for the drying operation, but was most efficient in terms of water use (10m3/t starch) due to water recycling between unit operations. The two small scale technologies were similar in terms of electricity use (59kWh/t starch), and relied on solar energy for drying. In contrast, their water consumption varied from 20 to 60m3/t starch due to differences in the design of the rasping and starch recovery (extraction) operations. The LCA characterizations, using the ReCiPe method, indicated that the main impact contributions were at the drying operation for the large scale technology, and at the extraction operation for the small scale technologies, mainly because of energy use, as well as water use in the case of the most water-intensive technology. Hence strategies to reduce the impacts of cassava starch production could focus on: Increasing the energy efficiency of the drying operation or replacing fossil energy with a renewable source (biogas), which can be produced from the factory wastewater; Improving the design of some unit operations with regards to water and energy efficiency; and Promoting the transfer and adoption of water recycling practices. (Texte intégral