Comparison study of constitutive models for overconsolidated clays

Widely distributed in natural deposits, the overconsolidated (OC) clays have attracted extensive experimental investigations on their mechanical behaviors, especially in the 1960s and 1970s. Based on these results, numerous constitutive models have also been established. These models generally fall into two categories: one based on the classical plasticity theory and the other the bounding surface (BS) plasticity theory, with the latter being more popular and successful. The BS concept and the subloading surface (SS) concept are the two major BS plasticity theories. The features of these two concepts and the representative models based on them are introduced, respectively. The unified hardening (UH) model for OC clays is also based on the BS plasticity theory but distinguishes itself from other models by the integration of the reference yield surface, unified hardening parameter, potential failure stress ratio, and transformed stress tensor. Modification is made to the Hvorslev envelop employed in the UH model to improve its capability of describing the behaviors of clays with extremely high overconsolidation ratio in this paper. The comparison among the BS model, SS model, and UH model is performed. Evidence shows that all these three models can characterize the fundamental behaviors of OC clays, such as the stress dilatancy, strain softening and attainment of the critical state. The UH model with the revised Hvorslev envelop has the fewest parameters which are identical to those of the modified Cam-Clay model

On the responsible subjects of self-driving cars under the sae system: An improvement scheme

The issue of how to identify the liability of subjects after a traffic accident takes place remains a puzzle regarding the SAE classification system. The SAE system is not good at dealing with the problem of responsibility evaluation; therefore, building a new classification system for self-driving cars from the perspective of the subject's liability is a possible way to solve this problem. This new system divides automated driving into three levels: i) assisted driving based on the will of drivers, ii) automated driving based on the will of the manufacturers, and iii) fully automated driving based on social will. The corresponding responsible subjects for level one, level two, and level three are the drivers, the manufacturers, and society, respectively

DNA damage-induced activation of ATM promotes β-TRCP-mediated Mdm2 ubiquitination and destruction

The Mdm2 oncoprotein promotes p53 ubiquitination and destruction. Yet, exact molecular mechanisms of Mdm2 destruction itself, under DNA damaging conditions, remain unclear. Recently, we identified SCFβ-TRCP as a novel E3 ligase that targets Mdm2 for ubiquitination and destruction in a Casein Kinase Iδ (CKIδ)-dependent manner. However, it remains elusive how the β-TRCP/CKIδ/Mdm2 signaling axis is regulated by DNA damage signals to govern p53 activity. Consistent with previous studies, we found that inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase, in turn, impaired DNA damage-induced Mdm2 destruction. Although phosphorylation of Mdm2 at Ser395 (an ATM phosphorylation site) facilitated Mdm2 interaction with β-TRCP, Ser395A-Mdm2 was degraded non-distinguishably from WT-Mdm2 by SCFβ-TRCP upon DNA damaging treatments. This indicates that in addition to phosphorylating Mdm2 at Ser395, ATM may govern Mdm2 stability through other unknown mechanisms. We further demonstrated that DNA damage-induced activation of ATM directly phosphorylated CKIδ at two well-conserved S/TQ sites, which promotes CKIδ nuclear localization to increase CKIδ-mediated phosphorylation of Mdm2, thereby facilitating subsequent Mdm2 ubiquitination by SCFβ-TRCP. Our studies provide a molecular mechanism of how ATM could govern DNA damage-induced destruction of Mdm2 in part by phosphorylating both Mdm2 and CKIδ to modulate SCFβ-TRCP–mediated Mdm2 ubiquitination. Given the pivotal role of Mdm2 in the negative regulation of p53, this work will also provide a rationale for developing CKIδ or ATM agonists as anti-cancer agents

SCFβ-TRCP-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway

The HECT domain-containing ubiquitin E3 ligase NEDD4 is widely expressed in mammalian tissues and plays a crucial role in governing a wide spectrum of cellular processes including cell growth, tissue development and homeostasis. Recent reports have indicated that NEDD4 might facilitate tumorigenesis through targeted degradation of multiple tumor suppressor proteins including PTEN. However, the molecular mechanism by which NEDD4 stability is regulated has not been fully elucidated. Here we report that SCFβ-TRCP governs NEDD4 protein stability by targeting it for ubiquitination and subsequent degradation in a Casein Kinase-I (CKI) phosphorylation-dependent manner. Specifically, depletion of β-TRCP, or inactivation of CKI, stabilized NEDD4, leading to down-regulation of its ubiquitin target PTEN and subsequent activation of the mTOR/Akt oncogenic pathway. Furthermore, we found that CKIδ-mediated phosphorylation of Ser347 and Ser348 on NEDD4 promoted its interaction with SCFβ-TRCP for subsequent ubiquitination and degradation. As a result, compared to ectopic expression of wild-type NEDD4, introducing a non-degradable NEDD4 (S347A/S348A-NEDD4) promoted cancer cell growth and migration. Hence, our findings revealed the CKI/SCFβ-TRCP signaling axis as the upstream negative regulator of NEDD4, and further suggested that enhancing NEDD4 degradation, presumably with CKI or SCFβ-TRCP agonists, could be a promising strategy for treating human cancers

Observed 3D Structure, Generation, and Dissipation of Oceanic Mesoscale Eddies in the South China Sea

Oceanic mesoscale eddies with horizontal scales of 50–300 km are the most energetic form of flows in the ocean. They are the oceanic analogues of atmospheric storms and are effective transporters of heat, nutrients, dissolved carbon, and other biochemical materials in the ocean. Although oceanic eddies have been ubiquitously observed in the world oceans since 1960s, our understanding of their three-dimensional (3D) structure, generation, and dissipation remains fragmentary due to lack of systematic full water-depth measurements. To bridge this knowledge gap, we designed and conducted a multi-months field campaign, called the South China Sea Mesoscale Eddy Experiment (S-MEE), in the northern South China Sea in 2013/2014. The S-MEE for the first time captured full-depth 3D structures of an anticyclonic and cyclonic eddy pair, which are characterized by a distinct vertical tilt of their axes. By observing the eddy evolution at an upstream versus downstream location and conducting an eddy energy budget analysis, the authors further proposed that generation of submesoscale motions most likely constitutes the dominant dissipation mechanism for the observed eddies