Amyloid fibrils have recently received attention due to their remarkable mechanical properties, which are highly correlated with their biological functions. We have studied the mechanical deformation mechanisms and properties of amyloid fibrils as a function of their length scales by using atomistic simulations. It is shown that the length of amyloid fibrils plays a role in their deformation and fracture mechanisms in such a way that the competition between shear and bending deformations is highly dependent on the fibril length, and that as the fibril length increases, so does the bending strength of the fibril while its shear strength decreases. The dependence of rupture force for amyloid fibrils on their length is elucidated using the Bell model, which suggests that the rupture force of the fibril is determined from the hydrogen bond rupture mechanism that critically depends on the fibril length. We have measured the toughness of amyloid fibrils, which is shown to depend on the fibril length. In particular, the toughness of the fibril with its length of ∼3 nm is estimated to be ∼30 kcal mol(-1) nm(-3), comparable to that of a spider silk crystal with its length of ∼2 nm. Moreover, we have shown the important effect of the pulling rate on the mechanical deformation mechanisms and properties of amyloid fibril. It is found that as the pulling rate increases, so does the contribution of the shear effect to the elastic deformation of the amyloid fibril with its length of <10 nm. However, we found that the deformation mechanism of the amyloid fibril with its length of >15 nm is almost independent of the pulling rate. Our study sheds light on the role of the length scale of amyloid fibrils and the pulling rate in their mechanical behaviors and properties, which may provide insights into how the excellent mechanical properties of protein fibrils can be determined.

To our knowledge, this is the first PPK study to suggest that GSTA1 polymorphisms in adults are associated with busulfan PK.

PurposeThis paper seeks to introduce a six‐sigma based methodology for the SCM domain which was developed and has been used in Samsung.Design/methodology/approachThe paper provides a detailed description of how and why a six‐sigma‐based methodology for the SCM domain was developed in Samsung and presents a real industry case to illustrate the usage of the methodology.FindingsIn Samsung, the effort and investment in synthesizing SCM and six sigma, and developing a unique six‐sigma‐based methodology to improve its SCM operation, have turned out to be fruitful. The Black Belt program has produced highly qualified and talented SCM specialists, who are currently training the methodology to members in their organizations and leading SCM projects. SCM projects are being prepared and conducted in a more disciplined way and their outcomes are continuously monitored and shared through the company's repository.Research limitations/implicationsTo generalize its usefulness, the methodology needs to be applied to the SCM projects of those companies whose organizational and cultural contexts are different from those of Samsung. In addition, the overview of an illustrative SCM project presented in the paper is brief due to space limitations.Practical implicationsToday, SCM is increasingly recognized as a strategic way to innovate a company's business operation. This paper shows that a methodology such as Samsung's SCM six sigma can be the key to conducting SCM projects in a more disciplined way and for fruitful outcomes.Originality/valueThe paper introduces a unique six‐sigma‐based methodology for the SCM domain which has been developed and applied in a leading global manufacturing, financial, and services conglomerate. This methodology could be adapted by other companies for their SCM projects to increase the likelihood of project success.

No abstract