Fixture knowledge model development and implementation based on a functional design approach

The development of a knowledge model applied to fixture design is a complex task. The main purpose of such model is the development of a knowledge-based application to assist fixture designers. It comprises a detailed specification of the types and structures of data involved in the execution of the inference process needed to create a fixture solution for machining a raw part. A development method together with a knowledge model for automating fixture design is proposed. The development was divided into three parts: Design Process Model, definition of Top-level functional functions and Product Knowledge Model. Adopting a functional design approach, the fixture design solution was created in two levels: functional and detailed. The functional level is based on fixture functional elements and the detailed one is based on fixture commercial elements. The definitions and concepts used in the application are specified in several Units of Knowledge (UoK) that comprises the Fixture Knowledge Model. Common Knowledge Analysis and Design Structuring (CommonKADS), Methodology and software tools Oriented to KBE Applications (MOKA), Integrated DEFinition for Function Modelling (IDEF0) and Unified Modelling Language (UML) are the methodologies and techniques used in the proposed method. Finally, a prototype KBE application for fixture design was developed

Differential genetic associations for systemic lupus erythematosus based on anti-dsDNA autoantibody production

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti-dsDNA autoantibody production, a SLE-related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti-dsDNA autoantibody positive (anti-dsDNA +, n = 811) and anti-dsDNA autoantibody negative (anti-dsDNA -, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti-dsDNA + SLE. Far fewer and weaker associations were observed for anti-dsDNA - SLE. For example, rs7574865 in STAT4 had an OR for anti-dsDNA + SLE of 1.77 (95% CI 1.57-1.99, p = 2.0E-20) compared to an OR for anti-dsDNA - SLE of 1.26 (95% CI 1.12-1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti-dsDNA + SLE and were not associated with anti-dsDNA - SLE. In conclusion, we identified differential genetic associations with SLE based on anti-dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti-dsDNA - SLE