Linkage analysis and haplotype mapping in interspecific mouse crosses (Mus musculus x Mus spretus) identified the gene encoding Aurora2 (Stk6 in mouse and STK15 in human) as a candidate skin tumor susceptibility gene. The Stk6 allele inherited from the susceptible M. musculus parent was overexpressed in normal cells and preferentially amplified in tumor cells from F(1) hybrid mice. We identified a common genetic variant in STK15 (resulting in the amino acid substitution F31I) that is preferentially amplified and associated with the degree of aneuploidy in human colon tumors. The Ile31 variant transforms rat1 cells more potently than the more common Phe31 variant. The E2 ubiquitin-conjugating enzyme UBE2N was a preferential binding partner of the 'weak' STK15 Phe31 variant form in yeast two-hybrid screens and in human cells. This interaction results in colocalization of UBE2N with STK15 at the centrosomes during mitosis. These results are consistent with an important role for the Ile31 variant of STK15 in human cancer susceptibility.

Fixture design is an important consideration in all manufacturing operations. Central to this design is selecting and positioning the locating points. While substantial literature exists in this area, most of it is for prismatic or solid workpieces. This paper deals with sheet metal fixture design. An “N-2-1” locating principle has been proposed and verified to be valid for deformable sheet metal parts as compared to the widely accepted “3-2-1” principle for rigid bodies. Based on the “N-2-1” principle algorithms for optimal fixture design are presented using finite element analysis and nonlinear programming methods to find the best “N” locating points such that total deformation of the deformable sheet metal is minimized. A simulation package called OFixDesign is introduced and numerical examples are presented to validate the “N-2-1” principle and optimal sheet metal fixture design approach.

STK15 (Aurora-A) is a serine/threonine kinase involved in mitotic chromosomal segregation. A genetic variant in STK15 T+91A (resulting in the amino acid substitution F31I) is associated with increased aneuploidy in colon tumors and cell transformation in vitro. Since this polymorphism plays a role in mitotic control-a process critical for all cancer types-we conducted association analyses for risk of cancer development of the colon, breast, prostate, skin, lung and esophagus in 10 independent case-control populations. We carried out a meta-analysis of these 10 case-control studies together with 5 additional published studies for a total of 9549 cases of breast, colon, ovarian, prostate, lung, esophageal and non-melanoma skin cancer and 8326 population or hospital-based controls. Meta-analysis of three colorectal cancer studies showed an increased risk in T+91A homozygotes (OR=1.50; 95% CI of 1.14-1.99). Meta-analysis of four breast cancer studies showed increased risk for T+91A homozygotes (OR=1.35, 95% CI of 1.12-1.64). The results of the multiple cancer type meta-analysis for all 15 studies combined were significant for cancer risk in both homozygotes and heterozygotes. The T+91A heterozygotes show an OR of 1.10 (95% CI of 1.03-1.18, P-value=0.006) and the T+91A homozygotes show an OR of 1.40 (95% CI of 1.22-1.59, P-value<0.001) for cancer risk. These results confirm that the STK15 T+91A variant is a low penetrance cancer susceptibility allele affecting multiple cancer types, and provide genetic evidence from large-scale human population studies that genetic stability at the chromosome level is an important determinant of cancer susceptibility. The data also underline the advantages of comparative association studies involving study populations from different ethnic groups for determination of disease risk.

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Fixtures are used to locate and hold workpieces during manufacturing. Because workpiece surface errors and fixture set-up errors (called source errors) always exist, the fixtured workpiece will consequently have position and/or orientation errors (called resultant errors). In this paper, we develop a variational method for robust fixture configuration design to minimize workpiece resultant errors due to source errors. We utilize both first-order and second-order workpiece geometry information to deal with two types of source errors, i.e., infinitesimal errors and small errors. Using the proposed variational approach, other fundamental fixture design issues, such as deterministic locating and total fixturing, can be regarded as integral parts of the robust design. Closed-form analytical solutions are derived and numerical examples are shown. By employing the nonlinear programming technique, simulation software called RFixDesign is developed. This paper presents a new procedure for robust fixture configuration design that contributes especially to fixture designs where deformation is not influential.

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An error compensation system has been developed to enhance the time-variant volumetric accuracy of a 3-axis machining center by correcting the existing machine errors through sensing, metrology, and computer control techniques. A general methodology has been developed to synthesize both the geometric and thermal errors of machines into a time-variant volumetric error model. Instead of the well-known 21 geometric error components, 32 machine linkage errors are formulated as a 4D error field including the space domain and the time domain. Different types of models are proposed for different kinds of thermal error components. A compensation controller based on an IBM/PC has been linked with a CNC controller to compensate for machine errors in real time. This scheme has been implemented on a horizontal machining center and has been shown, using metrology instruments, to improve the machine accuracy by an order of magnitude. A cut workpiece inspected using a coordinate measuring machine (CMM) has also shown that dimension errors have been reduced from 92.4 μm to 18.9 μm in a dimension of 404 × 310 mm2 and the depth difference of milled surfaces has been reduced from 196 μm to 8 μm.

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