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We study the crack-tip fields in a three-dimensional (3D) plate with a V-shaped crack employing Rajagopal's theory of elasticity with the strain-limiting effect. The classical linear elastic fracture mechanics (LEFM) theory bears a well-documented inconsistency, i.e., for a static crack problem under the traction-free boundary condition, the LEFM theory predicts singular crack-tip strains. Such results are inconsistent with the constitutive relation derived using the assumption of uniform bound for the strain values. Instead, Rajagopal's recent theory of elasticity provides implicit constitutive relations between the linearized strain and Cauchy stress in which one can impose an a-priori upper bound for strains. We formulate the strain-limiting theory comprehensively in this article. The linearized strain is expressed as a nonlinear function of the Cauchy stress. The equation for the equilibrium of the linear momentum under a special type of nonlinear constitutive relation reduces to a second-order quasilinear elliptic boundary value problem (BVP). Using a Picard-type linearization and a continuous Galerkin-type finite element technique, we solve several BVPs with tensile and shear displacement loading. The numerical results for the strains, the stresses, the stress intensity factor (SIF), and strain energy density (SED) are obtained for different Poisson values, strain-limiting parametric values, and the V-shaped angles. The growth of the near-tip strains is far less than that of stresses, and the results for both the SIF and SED are also consistent with the results from LEFM. Our work demonstrates that the framework of Rajagopal's theory of elasticity can provide a basis for developing physically meaningful and mathematically well-posed BVPs to study evolution of cracks, damage, nucleation, or failure in elastic bodies. [ABSTRACT FROM AUTHOR]

We consider the truncated geometric distribution and analyze the condition under which a nontrivial maximum likelihood (ML) estimator of the parameter p exists. Additionally, the uniqueness criterion of such an ML estimator is also investigated. Our results indicate that in order to ensure the existence of a nontrivial ML estimator, the sample mean should be smaller than the midpoint of the two boundary positions. Without such a condition, the ML estimator will only exist trivially at p = 0. Finally, we demonstrate that the same condition is also required for the existence of the method of moments estimator. Our results lead to a rigorous understanding of the two estimators and aid in the interpretation of experimental designs that incorporate the truncated geometric distribution. [ABSTRACT FROM AUTHOR]

Growth is a significant factor that results in deformations of tubular organs, and particular deformations associated with growth enable tubular organs to perform certain physiological functions. Configuring growth profiles that achieve particular deformation patterns is critical for analyzing potential pathological conditions and for developing corresponding clinical treatments for tubular organ dysfunctions. However, deformation-targeted growth is rarely studied. In this article, the human cervix during pregnancy is studied as an example to show how cervical thinning and dilation are generated by growth. An advanced hyperelasticity theory called morphoelasticity is employed to model the deformations, and a growth tensor is used to represent growth in three principle directions. The computational results demonstrate that both negative radial growth and positive circumferential growth facilitate thinning and dilation. Modeling such mixed growth represents an advancement beyond commonly used uniform growth inside tissues to study tubular deformations. The results reveal that complex growth may occur inside tissues to achieve certain tubular deformations. Integration of further biochemical and cellular activities that initiate and mediate such complex growth remains to be explored. [ABSTRACT FROM AUTHOR]

Angioedema is a tissue-swelling pathology due to rapid change in soft tissue fluid content. Its occurrence in the trachea is predominantly localized to the soft mucous tissue that forms the innermost tracheal layer. The biomechanical consequences, such as airway constriction, are dependent upon the ensuing mechanical interactions between all of the various tissues that comprise the tracheal tube. We model the stress interactions by treating the trachea organ as a three-tissue system consisting of swellable mucous in conjunction with nonswelling cartilage and nonswelling trachealis musculature. Hyperelastic constitutive modeling is used by generalizing the standard anisotropic, incompressible soft tissue framework to incorporate the swelling effect. Finite element stress analysis then proceeds with swelling of the mucous layer providing the driving factor for the mechanical analysis. The amount of airway constriction is governed by the mechanical interaction between the three predominant tissue types. The detailed stress analysis indicates the presence of stress concentrations near the various tissue junctions. Because of the tissue's nonlinear mechanical behavior, this can lead to material stiffness fluctuations as a function of location on the trachea. Patient specific modeling is presented. The role of the modeling in the interpretation of diagnostic procedures and the assessment of therapies is discussed. [ABSTRACT FROM AUTHOR]

We consider three different compressible versions of the conventional incompressible neo-Hookean material model. The different versions are not new and have been used in various model studies. They each give neo-Hookean behavior in an appropriate incompressible limit. The three versions each show some basic differences with respect to each other as regards the qualitative nature of the approach to the neo-Hookean limit. The purpose of this study is to exhibit these differences. [ABSTRACT FROM PUBLISHER]

The rate-limiting serine biogenesis enzyme PHGDH is overexpressed in cancers. Both serine withdrawal and genetic/pharmacological inhibition of PHGDH have demonstrated promising tumor-suppressing activities. However, the enzyme properties of PHGDH are not well understood and the discovery of PHGDH inhibitors is still in its infancy. Here, oridonin was identified from a natural product library as a new PHGDH inhibitor. The crystal structure of PHGDH in complex with oridonin revealed a new allosteric site. The binding of oridonin to this site reduced the activity of the enzyme by relocating R54, a residue involved in substrate binding. Mutagenesis studies showed that PHGDH activity was very sensitive to cysteine mutations, especially those in the substrate binding domain. Conjugation of oridonin and other reported covalent PHGDH inhibitors to these sites will therefore inhibit PHGDH. In addition to being inhibited enzymatically, PHGDH can also be inhibited by protein aggregation and proteasome-mediated degradation. Several tested PHGDH cancer mutants showed altered enzymatic activity, which can be explained by protein structure and stability. Overall, the above studies present new biophysical and biochemical insights into PHGDH and may facilitate the future design of PHGDH inhibitors. [ABSTRACT FROM AUTHOR]