Integrated Computational Materials Engineering OverviewThe automotive product design and manufacturing community is continually besieged by Herculean engineering, timing, and cost challenges. Nowhere is this more evident than in the development of designs and manufacturing processes for cast aluminum engine blocks and cylinder heads. Increasing engine performance requirements coupled with stringent weight and packaging constraints are pushing aluminum alloys to the limits of their capabilities. To provide high-quality blocks and heads at the lowest possible cost, manufacturing process engineers are required to fi nd increasingly innovative ways to cast and heat treat components. Additionally, to This article appears on the JOM web site (www.tms.org/JOMPT) in html format and includes links to additional on-line resources. remain competitive, products and manufacturing methods must be developed and implemented in record time. To bridge the gaps between program needs and engineering reality, the use of robust computational models in up-front analysis will take on an increasingly important role. This article describes just such a computational approach, the Virtual Aluminum Castings methodology, which was developed and implemented at Ford Motor Company and demonstrates the feasibility and benefi ts of integrated computational materials engineering.
Background
Anopheles sinensis is a major vector of malaria in China. The gamma-aminobutyric acid (GABA)-gated chloride channel, encoded by the RDL (Resistant to dieldrin) gene, is the important target for insecticides of widely varied structures. The use of various insecticides in agriculture and vector control has inevitably led to the development of insecticide resistance, which may reduce the control effectiveness. Therefore, it is important to investigate the presence and distribution frequency of the resistance related mutation(s) in An. sinensis RDL to predict resistance to both the withdrawn cyclodienes (e.g. dieldrin) and currently used insecticides, such as fipronil.MethodsTwo hundred and forty adults of An. sinensis collected from nine locations across Guangxi Zhuang Autonomous Region were used. Two fragments of An. sinensis RDL (AsRDL) gene, covering the putative insecticide resistance related sites, were sequenced respectively. The haplotypes of each individual were reconstructed by the PHASE2.1 software, and confirmed by clone sequencing. The phylogenetic tree was built using maximum-likelihood and Bayesian inference methods. Genealogical relations among different haplotypes were also analysed using Network 5.0.ResultsThe coding region of AsRDL gene was 1674 bp long, encoding a protein of 557 amino acids. AsRDL had 98.0% amino acid identity to that from Anopheles funestus, and shared common structural features of Cys-loop ligand-gated ion channels. Three resistance-related amino acid substitutions (A296S, V327I and T345S) were detected in all the nine populations of An. sinensis in Guangxi, with the 296S mutation being the most abundant (77–100%), followed by 345S (22–47%) and 327I (8–60%). 38 AsRDL haplotypes were identified from 240 individuals at frequencies ranging from 0.2 to 34.8%. Genealogical analysis suggested multiple origins of the 345S mutation in AsRDL.ConclusionsThe near fixation of the 296S mutation and the occurrence of the 327I and 345S mutations in addition to 296S, in all the nine tested An. sinensis populations in Guangxi, strongly indicate a risk of multiple insecticide resistance. The haplotype diversity plus genetic heterogeneities in the geographical distribution, and multiple origins of AsRDL alleles call for a location-customized strategy for monitoring and management of insecticide resistance.
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