The Self-Association of the KRAS4b Protein is Altered by Lipid-Bilayer Composition and Electrostatics

KRAS is a peripheral membrane protein that regulates multiple signaling pathways, and is mutated in ≈30 % of cancers. Transient self-association of KRAS is essential for activation of the downstream effector RAF and oncogenicity. The presence of anionic phosphatidylserine (PS) lipids in the membrane was shown to promote KRAS self-assembly, however, the structural mechanisms remain elusive. Here, we employed nanodisc bilayers of defined lipid compositions, and probed the impact of PS concentration on KRAS self-association. Paramagnetic NMR experiments demonstrated the existence of two transient dimer conformations involving alternate electrostatic contacts between R135 and either D153 or E168 on the “α4/5-α4/5” interface, and revealed that lipid composition and salt modulate their dynamic equilibrium. These dimer interfaces were validated by charge-reversal mutants. This plasticity demonstrates how the dynamic KRAS dimerization interface responds to the environment, and likely extends to the assembly of other signaling complexes on the membrane.     

A centrally cracked thin circular disk, Part I: 3D Elastic–plastic finite element analysis

A full field solution, based on small deformation, three-dimensional elastic–plastic finite element analysis of the centrally cracked thin disk under mode I loading has been performed. The solution for the stresses under small-scale yielding and lo!cally fully plastic state has been compared with the HRR plane stress solution. At the outside of the 3D zone, within a distance of rσ_o/J=18, HRR dominance is maintained in the presence of a significant amount of compressive stress along the crack flanks. Ahead of this region, the HRR field overestimate the stresses. These results demonstrate a completely reversed state of stress in the near crack front compared to that in the plane strain case. The combined effect of geometry and finite thickness of the specimen on elastic–plastic crack tip stress field has been explored. To the best of our knowledge, such an attempt in the published literature has not been made yet. For the qualitative assessment of the results some of the field parameters have been compared to the available experimental results of K, gives a fair estimate of the crack opening stress near the crack front at a distance of order 10⁻² in. On the basis of this analysis, the Linear Elastic Fracture Mechanics approach has been adopted in analyzing the fatigue crack extension experiments performed in the disk (Part II).     

Anisotropic plasticity for sheet metals using the concept of combined isotropic-kinematic hardening

Hill's 1948 anisotropic theory of plasticity (Hill, R., 1948. A theory of yielding and plastic flow of anisotropic metals. Proc. Roy. Soc. London A193, 281–297) is extended to include the concept of combined isotropic-kinematic hardening, and the objective of this paper is to validate the model so that it may be useful for analyses of sheet metal forming. Isotropic hardening and kinematic hardening may be experimentally observed in sheet metals, if yielding is defined by the proportional limit or by a small proof strain. In this paper, a single exponential term is used to describe isotropic hardening and Prager's linear kinematic hardening rule is applied for simplicity. It is shown that this model can satisfactorily describe both the yield stress and the plastic strain ratio, the R-ratio, observed in tension test of specimens cut at various angles measured from the rolling direction of the sheet. Kinematic hardening leads to a gradual change in the direction of the plastic strain increment, as the axial strain increases in the tension test; while in the traditional approach for sheet metal, this direction does not change due to the use of isotropic hardening.     

A constitutive model for orthotropic elasto-plasticity at large strains

Summary The paper presents a thermodynamically consistent constitutive model for elasto-plastic analysis of orthotropic materials at large strain. The elastic and plastic anisotropies are assumed to be persistent in the material but the anisotropy axes can undergo a rigid rotation due to large plastic deformations. The orthotropic yield function is formulated in terms of the generally nonsymmetric Mandel stress tensor such that its skew-symmetric part is additionally taken into account. Special attention is focused on the convexity of the yield surface resulting in the nine-dimensional stress space. Of particular interest are new convexity conditions which do not appear in the classical theory of anisotropic plasticity. They impose additional constraints on the material constants governing the plastic spin. The role of the plastic spin is further studied in simple shear accompanied by large elastic and large plastic deformations. If the plastic spin is neglected, the shear stress response is characterized by oscillations with an amplitude strictly dependent on the degree of the plastic anisotropy.accepted for publication 2 March 2004     

Continuum theory of dislocations revisited

The paper continues the discussion of continuum theory of dislocations suggested by Berdichevsky and Sedov (PMM 31(6): 981–1000, 1967). The major new points are: the choice of energy, the variational form of the governing dynamical equations, the variational principle for the final plastic state.     

三山岛金矿控矿断层F1的力学性质及补强措施

作者以正在开采中的三山岛金矿采场为研究对象，分析矿区开采过程中的岩体结构特征及重力方向矿柱、护顶矿柱与控矿断层F1断层泥及其上覆岩体之间的关系和力学机制。通过试验研究了断层泥的物质成分和力学性质，总结了力学特性与断层泥厚度及含水量之间的关系。在此基础上提出锚固大于中倾角的结构面，提高结构面的抗滑阻力；增加含有高、陡倾角结构面矿柱的刚度等对矿柱的补强措施。对护顶矿柱提出预先锚固；分阶段开采的补强方法。在裂隙密集带设置排水设施，改善断层泥的赋存条件，提高它的力学性能。     

A phenomenological model of electrorheological fluids

The fundamental assumption of the paper is that the extra stress tensor of an electrorheological fluid is an isotropic tensor valued function of the rate of strain tensor D and the vector n (which characterizes the orientation and length N of the fibers formed by application of an electric field). The resulting constitutive equation for is supplemented by the solution of the previously studied time evolution equation for n. Plastic behavior for the shear and normal stresses is predicted. Anticipating that the action of increasing shear rate is i) to orient the fibers more and more in the direction of flow and ii) simultaneously to break up the fibers leads to the conclusion that for the same behavior is encountered as without an electric field. Using realistically possible approximation formulas for the dependence of and N on leads to the Bingham behavior for and power law behavior for large shear rates.

Numerical analysis of diffuse and localized necking in orthotropic sheet metals

In the present paper the diffuse and localized necking models according to Swift [Swift, H.W., 1952. Plastic instability under plane stress, Journal of the Mechanics and Physics of Solids, 11–18], Hill [Hill, R., 1952. On discontinuous plastic states, with special reference to localized necking in thin sheets. Journal of the Mechanics and Physics of Solids 1, 19–30] and Marciniak and Kuczyński [Marciniak, Z., Kuczyński, K., 1967. Limit strains in the process of stretch-forming sheet metal. International Journal of Mechanical Sciences 9, 609–620], respectively, are considered. A theoretical framework for the mentioned models is proposed that covers rigid–plastic as well as elastic–plastic constitutive modelling using various advanced phenomenological yield functions that are able to account very accurately for plastic anisotropy. The mentioned necking models are applied to different orthotropic sheet metals in order to assess their predictive capabilities and to stress out some potential sources for discrepancies between simulations and experiments. In particular, the impact of the applied hardening curve and the equibiaxial r-value, which was recently introduced by Barlat [Barlat, F., Brem, J.C., Yoon, J.W., Chung, K., Dick, R.E., Choi, S.-H., Pourboghrat, F., Chu, E., Lege, D.J., 2003. Plane stress yield function for aluminium alloy sheets – part 1: theory. International Journal of Plasticity 19, 297–1319], on formability prediction is investigated. Furthermore, the impact of the Portevin–LeChatelier effect on the formability of aluminum sheet metals is discussed.