Computer-Aided Design/Tolerancing Integration: A Novel Tolerance Analysis Model of Assemblies With Composite Positional Defects and Deformations of Nonrigid Parts

Nowadays, the tolerancing integration in computer-aided design (CAD) tools remains among the major goals of mechanical manufacturers. In the virtual product development, ideal and rigid models are used in the digital mockup (DMU). Hence, research works developed integrated CAD models for tolerance analysis, while considering manufacturing defects. However, the tolerance analysis in the case of composite positional tolerance for feature patterns, commonly used in the industry, becomes a difficult activity with the consideration of parts deformations. Thus, this paper presents a novel CAD model for the tolerance analysis considering composite positional defect of features set and nonrigid component deformations due to external mechanical loads. The modeling of rigid components with dimensional defects is established based on the numerical perturbation method. Indeed, the relationships between driving and driven dimensions are determined to obtain the configurations in maximum and least material of the CAD model. Thereafter, the geometrical deviations are modeled by face displacements. The modeling of composite positional errors is performed while respecting the feature relating position tolerance zone framework and the pattern-location tolerance zone framework constraints, as well as the maximum or least material condition. The deviations caused by nonrigid part deformations are considered by the integration of finite element results into the CAD model. The realistic configurations of the assembly are obtained after the updating of mating constraints between rigid and nonrigid parts with defects. The composite positional tolerance is analyzed with the simulation of relative motion between parts. A case study is proposed to evaluate the developed tolerancing method.

Family permutation profiling identifies a dynamic protein domain as functionally tolerant to increased conformational entropy

ABSTRACTTo investigate whether adenylate kinase (AK) homologs differ in their functional tolerance to mutational lesions that alter dynamics, we subjected three homologs having a range of thermostabilities to random circular permutation and evaluated where new protein termini were non-disruptive to activity using a cellular selection and deep mutational scanning. Analysis of the positional tolerance to new termini, which increase local conformational entropy by breaking peptide bonds, showed that bonds were either functionally sensitive to cleavage across all three homologs, differentially sensitive, or uniformly tolerant. The mobile AMP binding domain, which displays the highest calculated contact energies (frustration), presented the greatest tolerance to new termini across all AKs. In contrast, retention of function in the lid and core domains was more dependent upon AK melting temperature. Thus, regions of high energetic frustration tolerated increases in conformational entropy in a manner that was less dependent on thermostability than regions of lower frustration. Our results suggest that family permutation profiling identifies primary structure that has been selected by evolution for high frustration that is critical to enzymatic activity. They also illustrate how deep mutational scanning can be applied to protein homologs in parallel to learn how topology and function govern mutational tolerance.

Protein tolerance to random circular permutation correlates with thermostability and local energetics of residue-residue contacts

Adenylate kinase (AK) orthologs with a range of thermostabilities were subjected to random circular permutation, and deep mutational scanning was used to evaluate where new protein termini were nondisruptive to activity. The fraction of circularly permuted variants that retained function in each library correlated with AK thermostability. In addition, analysis of the positional tolerance to new termini, which increase local conformational flexibility, showed that bonds were either functionally sensitive to cleavage across all homologs, differentially sensitive, or uniformly tolerant. The mobile AMP-binding domain, which displays the highest calculated contact energies, presented the greatest tolerance to new termini across all AKs. In contrast, retention of function in the lid and core domains was more dependent upon AK melting temperature. These results show that family permutation profiling identifies primary structure that has been selected by evolution for dynamics that are critical to activity within an enzyme family. These findings also illustrate how deep mutational scanning can be applied to protein homologs in parallel to differentiate how topology, stability, and local energetics govern mutational tolerance.

An Improved Features of Health Screening Test System for Malaysian Social Security Organisation (SOCSO) Programme

The purpose of this paper is to improve the features of Health Screening Test System (HSTS) on Social Security Organization (SOCSO) program as physical evaluation for musculoskeletal disable workers (MSDs). SOCSO existing functional testing system are not suitable because of the evaluation was recorded manually peg board too high for Asian people. The occupational therapist whose involve in all the procedures is just doing the judgment in times to determine the capability of the patients. The functional capacity evaluation (FCE) technique is based on the functional range of motion evaluation that consist of positional tolerance respecting to time-motion testing on HSTS peg board and it is by referring to the original work movement. The main features of HSTS are able to measure speed, acceleration and evaluation of SOCSO’s patients for returning to work based on SOCSO’s requirement. In order to validate the accuracy of the proposed model, HSTS is used to evaluate the patient’s positional tolerance and then the result would be compare over the time frame which is Method Time Measurement (MTM) standard. This method is able to provide information and feedback for therapies as a status of patients. It is found that the proposed model is superior in getting the accurate time test for patient’s movements besides practicable and suitable for physical evaluation on MSD patients.