Beclin 1, LC3 and P62 Expression in Equine Sarcoids

Background: It is well known that δ-bovine papillomaviruses (BPV-1, BPV-2 and BPV-13) are one of the major causative agents of equine sarcoids, the most common equine skin tumors. Different viruses, including papillomaviruses, evolved ingenious strategies to modulate autophagy, a complex process involved in degradation and recycling of old and damaged material. Methods: The aim of this study was to evaluate, by immunohistochemistry (IHC) and Western blot (WB) analysis, the expression of the main related autophagy proteins (Beclin 1, protein light chain 3 (LC3) and P62), in 35 BPV1/2 positive equine sarcoids and 5 BPV negative normal skin samples. Results: Sarcoid samples showed from strong-to-moderate cytoplasmic immunostaining, respectively, for Beclin 1 and P62 in >60% of neoplastic fibroblasts, while LC3 immunostaining was weak to moderate in ≤60% of neoplastic fibroblasts. Western blot analysis confirmed the specificity of the antibodies and revealed no activation of autophagic flux despite Beclin 1 overexpression in sarcoid samples. Conclusion: Results could suggest the activation of the initial phase of autophagy in equine sarcoids, and its impairment during the following steps. The impairment of autophagy could lead to a selection of a quiescent population of fibroblasts, which survive longer in a hypoxic microenvironment and produced more and/or altered collagen.

Modeling of influence of planar defects on plasticity of powder materials by computational methods of micromechanics

Based on the energy concept of the critic stress state, a three-parameter model of plasticity of the Cam-Clay type was formulated. For this phenomenological model, the dependences of the determining parameters on the porosity and damage were found by the method of micromechanical averaging on the unit cell corresponding to the porous damaged material of powder origin. The plastic multi-responce (different yield strength in tension and compression) behavior of this material is found by micromechanical averaging on a unit cell. According to the mechanics of composites, the geometry of the cell represents the structure of a heterogeneous material and the boundary conditions on a unit cell make it possible to relate the stress-strain state at the macro- and meso-level. The averaging was carried out by computer simulation using the finite element method with an adaptive mesh, which was automatically condensed in places of a large gradient of the stress-strain state. The structure of the representative cell corresponds to a powder origin material with "imperfect", partially stratified, interparticle contacts. In the proposed model the rheological response of a porous damaged material is specified by three moduli, and the structure of such a material is described by two internal state parameters: porosity and the degree of delamination of interparticle contacts. That is, the rheological moduli are functions of porosity and damage. Accordingly, a number of values of each of the moduli were calculated for a certain discrete range of density and damage. The advantage of this approach is precisely in focusing on powder origin materials and not generally on any damaged materials, which makes it possible to take into account the real structure of the damaged material using the methods of mechanics of microheterogeneous materials. According to the simulation results, in particular, it was found that the yield strength for shear is significantly (30%) less sensitive to damage than the yield strength for uniaxial tension. Keywords: theory of plasticity, powder materials, micromechanics, damaged materials, stress-strain state.

Restructuring of the plasma membrane upon damage by LC3-associated macropinocytosis

The plasma membrane shapes and protects the eukaryotic cell from its surroundings and is crucial for cell life. Although initial repair mechanisms to reseal injured membranes are well established, less is known about how cells restructure damaged membranes in the aftermath to restore homeostasis. Here, we show that cells respond to plasma membrane injury by activating proteins associated with macropinocytosis specifically at the damaged membrane. Subsequent to membrane resealing, cells form large macropinosomes originating from the repair site, which eventually become positive for autophagy-related LC3B protein. This process occurs independent of ULK1, ATG13, and WIPI2 but dependent on ATG7, p62, and Rubicon. Internalized macropinosomes shrink in the cytoplasm, likely by osmotic draining, and eventually fuse with lysosomes. We propose that a form of macropinocytosis coupled to noncanonical autophagy, which we term LC3-associated macropinocytosis (LAM) functions to remove damaged material from the plasma membrane and restore membrane integrity upon injury.

A geometrically inspired model for brittle damage in compressible elastomers

Regularized continuum damage models such as those based on an order parameter (phase field) have been extensively used to characterize brittle damage of compressible elastomers. However, the prescription of the surface integral and the degradation function for stiffness lacks a physical basis. In this article we propose a continuum damage model that draws upon the postulate that a damaged material could be mathematically described as a Riemannian manifold. Working within this framework with a well defined Riemannian metric designed to capture features of isotropic damage, we prescribe a scheme to prevent damage evolution under pure compression. The result is a substantively reduced stiffness degradation due to damage before the peak response and a faster convergence rate with the length scale parameter in comparison with a second order phase field formulation that involves a quadratic degradation function. We also validate this model using results of tensile experiments on double notched plates.

MODELING OF THE FATIGUE DURABILITY OF STRUCTURAL ALLOYS UNDER TWO-FREQUENCY LOADING

The processes of fatigue life of polycrystalline structural alloys under the combined action of low- and high-cycle fatigue mechanisms are considered. From the standpoint of damaged medium mechanics (DMM), a mathematical model has been developed that describes the processes of plastic deformation and the accumulation of fatigue damage. The DMM model consists of three interrelated parts: relations that determine the cyclic elastoplastic behavior of the material, taking into account the dependence on the fracture process; equations describing the kinetics of fatigue damage accumulation; criterion for the strength of the damaged material. Variant of the constitutive relations for elastoplasticity is based on the concept of a microplastic loading surface in the von Mises form and the principle of the gradient of the plastic strain rate vector to the surface at the loading point. This version of the equations of state reflects the main effects of the process of cyclic plastic deformation of the material for arbitrary complex loading trajectories. A variant of the kinetic equations for the accumulation of fatigue damage is based on the introduction of a scalar damage parameter, is based on energy principles and takes into account the main effects of the formation, growth and fusion of microdefects under arbitrary complex loading conditions. A unified form of the evolutionary equation for the accumulation of fatigue damages for low-cycle and high-cycle fatigue is proposed. As a criterion for the strength of the damaged material, the condition for reaching the critical value of the damage is used. To assess the reliability and determine the limits of applicability of the constitutive relations of the DMM, numerical studies of the processes of accumulation of fatigue damage by cyclic inelastic deformation and fatigue failure of steel 20 and 08Х18Н12Т were carried out under single-frequency loading of the upper frequency and two-frequency loading with different amplitude ratios. And the comparison of the obtained numerical results with the data of field experiments is carried out. The results of comparing the calculated and experimental data showed that the developed model of the damaged environment reliably describes the durability of structures under the action of low- and high-cycle fatigue mechanisms.

Failure analysis and countermeasures of the SCM435 high-tension bolt of three-step injection mold

PurposeThe objective of this study was to perform damage analysis of SCM435 high-tension bolts connecting upper and lower parts of a three-stage injection molding machine.Design/methodology/approachDamage material used in this study was a SCM435 high-strength bolt connecting upper and lower molds of a three-stage injection mold. Causes of damage were determined by macroscopic observation. Microstructure observation was done using a metallic microscope, scanning electron microscope (SEM, S-2400, HiTachi, Japan), energy dispersive X-ray spectroscopy (EDS, Kevex Ltd., Sigma) and Vickers hardness tester (HV-114, Mitutoyo). Fatigue limit of the damaged material was evaluated using equivalent crack length.FindingsBolts were fractured by cyclic bending stress in the observation of ratchet marks and beach marks. The damaged specimen showed an acicular microstructure. Impurity was observed. Chromium carbide was observed near the crack origin. Both shape parameters of the Vickers hardness were similar. However, the scale parameter of the damaged specimen was about smaller than that of the as-received specimen. Much degradation occurred in the damaged specimen. Bolts should undergo accurate heat treatment to prevent the formation of chromium carbide. They must prevent the action of dynamic stresses. Bolts need accurate tightening and accuracy of heat treatment. Screws require compression residual stress due to peening.Originality/valueThis study conducted failure analysis of damaged SCM435 bolts connecting upper and lower parts of the three-stage injection mold. Fatigue limit of the damaged material was evaluated using equivalent crack length. In order to control this fracture, accurate tightening of bolts, accuracy of heat treatment and screws are required for compression residual stress due to peening.

A review of the genus Chrastoblatta Saussure et Zehntner, 1895 (Dictyoptera: Ectobiidae: Blattellinae)

This paper gives a review of the insufficiently studied genus Chrastoblatta Saussure et Zehntner, 1895. The genus Chrastoblatta was described from Madagascar (environs of Antananarivo) and includes two species: Ch. tricolor Saussure et Zehntner, 1895 and Ch. dimidiata (Saussure, 1863). This contribution is based on the study of a series of paralectotypes of Ch. tricolor and syntypes of Ch. dimidiata from The Muséum d’histoire naturelle in Geneva. Additional specimens of Ch. tricolor were found in the collection of the Zoological Institute of the Russian Academy of Sciences in Saint Petersburg. Detailed morphological description of the type species, Ch. tricolor, is given. Particular attention is paid to the structure of the male and female genitalia, which are described for the first time. Chrastoblatta dimidiata is briefly described due to insufficient and damaged material, but it is probably closely related to the type species. The genus Chrastoblatta is characterized by a peculiar structure of the wide and flat head, hind tibiae with concavity at the apex, a distinctly reduced 4th segment of the tarsi, an asymmetrical hypandrium, and robust, curved styli. The presence of not inverted genitalia suggests the placement of Chrastoblatta in the subfamily Blattellinae. At the present time, the differential diagnosis of the genus Chrastoblatta based on characters of the male and female genitalia cannot be compiled due to insufficient knowledge of other Madagascan ectobiid.

Investigation of Systems Weakened by Kinked Cracks

Прочность летательных аппаратов любых типов — важнейший вопрос безопасности полетов. Наличие скрытых дефектов в материале существенно влияет на прочность при различных нагрузках. Важными характеристиками прочности материалов с дефектами являются скорость и направление роста трещины, а также величина критической нагрузки (коэффициента интенсивности напряжений), при которой начинается рост трещины. В данной работе исследуется трехмерная упругая среда, ослабленная системой плоских трещин и одной трещиной с изгибом. В качестве численного метода был выбран метод граничных элементов, а именно метод разрывных перемещений. Код реализован на C++. Было проведено сравнение с известными аналитическими результатами. Изучено поведение трещин при изгибе при различных нагрузках. Structural strength of aircraft is a key aspect of flight safety. Hidden defects in the material significantly affect its strength under various loads. The crack growth rate and direction, and the crack growth threshold load (stress intensity factor) affect the strength of the damaged material. This study investigates a 3D elastic structure weakened by a system of flat cracks and a kinked crack. The numerical method used was the boundary element method, specifically, the displacement discontinuity method. The code was developed with C++. The results were compared against the available analytic results. The behavior of cracks under bending and a range of loading conditions was studied.

Efficiency Analysis of Fractional KiloWatt Reluctance Motors with Various Frame Sizes, Taking into Account the Impact of the Punching Process

The need to reduce electricity consumption by electrical devices, including electric motors, is the reason for the development of new designs. Designers strive to improve operational parameters, including efficiency, using, for example, new types of magnetic materials, new types of stator windings, etc. Currently, in mass production, motor cores are made of punched laminations—punching causes damage of core parts. For motors of relatively large geometrical sizes, this effect is ignored during design. For motors having small dimensions, this negative effect results in a reduction in efficiency, which is mostly small for this type of motor. In this paper, the authors propose a new rapid algorithm based on simple measurements to determine the material characteristics of the damaged material part. Then, using them in the FEM models, they determine the efficiency of motors with various powers and frame sizes. On this basis, the conclusions are formulated, they may be helpful for motor designers.