Simplified Numerical Model for Determining Load-Bearing Capacity of Steel-Wire Ropes.

Steel-wire rope is a mechanical component that has versatile uses and on which human lives depend. One of the basic parameters that serve to describe the rope is its load-bearing capacity. The static load-bearing capacity is a mechanical property characterized by the limit static force that the rope is able to endure before it breaks. This value depends mainly on the cross-section and the material of the rope. The load-bearing capacity of the entire rope is obtained in tensile experimental tests. This method is expensive and sometimes unavailable due to the load limit of testing machines. At present, another common method uses numerical modeling to simulate an experimental test and evaluates the load-bearing capacity. The finite element method is used to describe the numerical model. The general procedure for solving engineering tasks of load-bearing capacity is by using the volume (3D) elements of a finite element mesh. The computational complexity of such a non-linear task is high. Due to the usability of the method and its implementation in practice, it is necessary to simplify the model and reduce the calculation time. Therefore, this article deals with the creation of a static numerical model which can evaluate the load-bearing capacity of steel ropes in a short time without compromising accuracy. The proposed model describes wires using beam elements instead of volume elements. The output of modeling is the response of each rope to its displacement and the evaluation of plastic strains in the ropes at selected load levels. In this article, a simplified numerical model is designed and applied to two constructions of steel ropes, namely the single strand rope 1 × 37 and multi-strand rope 6 × 7-WSC.

Study of Optimal Cam Design of Dual-Axle Spring-Loaded Camming Device.

The spring-loaded camming device (SLCD), also known as "friend", is a simple mechanism used to ensure the safety of the climber through fall prevention. SLCD consists of two pairs of opposing cams rotating separately, with one (single-axle SLCD) or two (dual-axle SLCD) pins connecting the opposing cams, a stem, connected to the pins, providing the attachment of the climbing rope, springs, which simultaneously push cams to a fully expanded position, and an operating element controlling the cam position. The expansion of cams is thus adaptable to allow insertion or removal of the device into/from a rock crack. While the pins, stem, operating element, and springs can be considered optimal, the (especially internal) shape of the cam allows space for improvement, especially where the weight is concerned. This paper focuses on optimizing the internal shape of the dual-axle SLCD cam from the perspective of the weight/stiffness trade-off. For this purpose, two computational models are designed and multi-step topology optimization (TOP) are performed. From the computational models' point of view, SLCD is considered symmetric and only one cam is optimized and smoothened using parametric curves. Finally, the load-bearing capacity of the new cam design is analyzed. This work is based on practical industry requirements, and the obtained results will be reflected in a new commercial design of SLCD.

Special Issue: Selected Papers from Experimental Stress Analysis 2020.

The contemporary way of living brings about increasing demands on materials used in our everyday lives [...].

Damage Analysis of Composite CFRP Tubes Using Acoustic Emission Monitoring and Pattern Recognition Approach.

The acoustic emission method has been adopted for detection of damage mechanisms in carbon-fiber-reinforced polymer composite tubes during the three-point bending test. The damage evolution process of the individual samples has been monitored using the acoustic emission method, which is one of the non-destructive methods. The obtained data were then subjected to a two-step technique, which combines the unsupervised pattern recognition approach utilizing the short-time frequency spectra with the boundary curve enabling the already clustered data to be additionally filtered. The boundary curve identification has been carried out on the basis of preliminary tensile tests of the carbon fiber sheafs, where, by overlapping the force versus time dependency by the acoustic emission activity versus time dependency, it was possible to identify the boundary which will separate the signals originating from the fiber break from unwanted secondary sources. The application of the presented two-step method resulted in the identification of the failure mechanisms such as matrix cracking, fiber break, decohesion, and debonding. Besides the comparison of the results with already published research papers, the study presents the comprehensive parametric acoustic emission signal analysis of the individual clusters.

Parameters Identification of the Anand Material Model for 3D Printed Structures.

Currently, there is an increasing use of machine parts manufactured using 3D printing technology. For the numerical prediction of the behavior of such printed parts, it is necessary to choose a suitable material model and the corresponding material parameters. This paper focuses on the determination of material parameters of the Anand material model for acrylonitrile butadiene styrene (ABS-M30) material. Material parameters were determined using the genetic algorithm (GA) method using finite element method (FEM) calculations. The FEM simulations were subsequently adjusted to experimental tests carried out to achieve the possible best agreement. Several experimental tensile and indentation tests were performed. The tests were set up in such a way that the relaxation and creep behaviors were at least partially captured. Experimental tests were performed at temperatures of 23 °C, 44 °C, 60 °C, and 80 °C. The results obtained suggest that the Anand material model can also be used for ABS-M30 plastic material, but only if the goal is not to detect anisotropic behavior. Future work will focus on the search for a suitable material model that would be able to capture the anisotropic behavior of printed plastic materials.

Billet Straightening by Three-Point Bending and Its Automation.

This paper presents the current results of cooperation focused on automatic billet straightening machine development. First, an experimental study of three-point bending realized on small specimens is presented to explain the basic ideas of the straightening. Then, the main regimes of straightening and the algorithm itself are described together. Subsequent finite element simulations of operational experiments show the applicability of the developed theory. The significance of material parameters estimation is depicted in this work. At least four parameters have to be properly determined for a new material in the straightening process.

Surface Magnetostriction of FeCoB Amorphous Ribbons Analyzed Using Magneto-Optical Kerr Microscopy.

Surface sensitive magneto-optical Kerr microscopy completed with the special self-made sample holder is used for studying the magneto-elastic behaviour in the surface of the as-quenched amorphous Fe73Co12B15 alloy. The 10, 5, and 3 mm wide and approximately 34 µm thick ribbons were prepared by the conventional planar flow casting process. The experimental setup allows for a simultaneous application of an external magnetic field in the directions parallel and perpendicular to the ribbon axis and of compression stress from one side of the sample, resulting in tensile stress in opposite side. The distributions of tensile stresses in the measured surface were modelled by the finite element method. The observed changes of the magnetic domains and hysteresis loop anisotropy field under applied stress are evaluated using the Becker-Kersten method. This resulted in the determination of the local surface magnetostrictive coefficient from an area of about 200 µm in diameter. The obtained values ranged between 37-60 ppm and were well comparable with the bulk value presented in the literature.

Validation of Multiaxial Fatigue Strength Criteria on Specimens from Structural Steel in the High-Cycle Fatigue Region.

The paper describes results of fatigue strength estimates by selected multiaxial fatigue strength criteria in the region of high-cycle fatigue, and compares them with own experimental results obtained on hollow specimens made from CSN 41 1523 structural steel. The specimens were loaded by various combinations of load channels comprising push-pull, torsion, bending and inner and outer pressures. The prediction methods were validated on fatigue strengths at seven different numbers of cycles spanning from 100,000 to 10,000,000 cycles. No substantial deviation of results based on the selected lifetime was observed. The PCRN method and the QCP method provide best results compared with other assessed methods. The results of the MMP criterion that allows users to evaluate the multiaxial fatigue loading quickly are also of interest because the method provides results only slightly worse than the two best performing solutions.

Modeling and Testing of Flexible Structures with Selected Planar Patterns Used in Biomedical Applications.

Flexible structures (FS) are thin shells with a pattern of holes. The stiffness of the structure in the normal direction is reduced by the shape of gaps rather than by the choice of the material based on mechanical properties such as Young's modulus. This paper presents virtual prototyping of 3D printed flexible structures with selected planar patterns using laboratory testing and computer modeling. The objective of this work is to develop a non-linear computational model evaluating the structure's stiffness and its experimental verification; in addition, we aimed to identify the best of the proposed patterns with respect to its stiffness: load-bearing capacity ratio. Following validation, the validated computational model is used for a parametric study of selected patterns. Nylon-Polyamide 12-was chosen for the purposes of this study as an appropriate flexible material suitable for 3D printing. At the end of the work, a computational model of the selected structure with modeling of load-bearing capacity is presented. The obtained results can be used in the design of external biomedical applications such as orthoses, prostheses, cranial remoulding helmets padding, or a new type of adaptive cushions. This paper is an extension of the conference paper: "Modeling and Testing of 3D Printed Flexible Structures with Three-pointed Star Pattern Used in Biomedical Applications" by authors Repa et al.

Cathepsin D: Autoantibody profiling as a diagnostic marker for cancers.

Current diagnostic assays for many cancers are antigen-based and rely on the detection of circulating proteins that are associated with a particular cancer. These assays depend on the expression, synthesis, and release of specific proteins by cells (e.g., tumor cells) through either active secretion or shedding, or as a consequence of cell death (either necrosis or apoptosis). As such, these antigenic proteins must "escape" the primary site of disease, saturate the antigen-processing capacity of the individual's immune components, gain access to the circulation, and reach a sufficient steady-state concentration to be detected by enzyme- or radiolabel-based immunoassays. These events usually occur after the initial establishment of disease. Thus, and despite the fact that certain specific antigenic epitopes exhibit common recognition among patients with the same tumor types, the use of these antigen-based cancer assays has not been widely accepted in clinical practice, and many individual countries differ in the use of these potential diagnostic factors. Lately, an increasing number of studies demonstrated that procathepsin D secreted from cancer cells, acts as a mitogen on cancer cells and stimulates their pro-invasive and pro-metastatic properties. In this report, we focused on the possibility to use anti-procathepsin D autoantibodies as a diagnostic and/or predictive marker for cancers.

Procathepsin d involvement in chemoresistance of cancer cells.

BACKGROUND: The role of pCD in cancer has been studied for a long time. We have focused on the hypothesis that increased expression and/or secretion of pCD in cancer cells causes increased chemoresistance to apoptosis inducing molecules. AIM: The aim was to evaluate the effects of pCD expression/release on chemoresistance. MATERIALS AND METHODS: We tested the LC(50) values for various transfectants of breast cancer cell line MDA-MB-231 as well as effects of exogenous additions of pCD, its mutants, pepstatine, antibodies, and Brefeldin on the resistance. RESULTS: We found that pCD levels can be correlated with chemoresistance, the pro-resistant activity seems to be localized outside the cells, proteolytic activity is not involved, and PI3-Akt signaling has an important role in antiapoptotic effects of pCD. CONCLUSION: We can conclude that overexpression of pCD has strong influence on increased resistance of tumor cells. This could, in fact, be an important contribution in the possible use of pCD level determination for prognostic and/or therapeutic purposes.

Procathepsin D as a tumor marker, anti-cancer drug or screening agent.

Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas, affecting multiple features of tumor cells including proliferation, invasion, metastasis and apoptosis. As more and more attention has been focused on potential use of pCD in clinical practice, we devoted this paper to summarize the three major potentials of pCD--tumor marker, potential drug and screening agent. Despite more than 20 years of studies and numerous reports of the association between pCD level and tumor size, tumor grade, tumor aggressiveness, and incidence of metastasis, pCD is still not used as a marker of cancer development. This is due to problems in distinguishing between pCD expressed by cancer derived cells and normal tissue cells and in the exact measuring of its different molecular forms (pCD, single chain cathepsin D (CD) and two chain CD) in tumor tissue. Numerous studies demonstrated that pCD secreted from cancer cells affects multiple stages of tumor progression. Subsequent data showing that inhibition of pCD secretion from cancer cells can inhibit cancer cell growth in vitro and in vivo suggested the possibility of using pCD suppression in clinical practice. A third possibility of using pCD in clinical practice is represented by the use of anti-pCD autoantibodies in screening cancer patients or in correlation with the level of these antibodies with the progress of cancer disease. Despite the fact that preliminary findings suggested such correlation, more detailed studies revealed significant setbacks.

Cathepsin D--many functions of one aspartic protease.

For years, it has been held that cathepsin D (CD) is involved in rather non-specific protein degradation in a strongly acidic milieu of lysosomes. Studies with CD knock-out mice revealed that CD is not necessary for embryonal development, but it is indispensable for postnatal tissue homeostasis. Mutation that abolishes CD enzymatic activity causes neuronal ceroid lipofuscinosis (NCL) characterized by severe neurodegeneration, developmental regression, visual loss and epilepsy in both animals and humans. In the last decade, however, an increasing number of studies demonstrated that enzymatic function of CD is not restricted solely to acidic milieu of lysosomes with important consequences in regulation of apoptosis. In addition to CD enzymatic activity, it has been shown that apoptosis is also regulated by catalytically inactive mutants of CD which suggests that CD interacts with other important molecules and influences cell signaling. Moreover, procathepsin D (pCD), secreted from cancer cells, acts as a mitogen on both cancer and stromal cells and stimulates their pro-invasive and pro-metastatic properties. Numerous studies found that pCD/CD level represents an independent prognostic factor in a variety of cancers and is therefore considered to be a potential target of anti-cancer therapy. Studies dealing with functions of cathepsin D are complicated by the fact that there are several simultaneous forms of CD in a cell-pCD, intermediate enzymatically active CD and mature heavy and light chain CD. It became evident that these forms may differently regulate the above-mentioned processes. In this article, we review the possible functions of CD and its various forms in cells and organisms during physiological and pathological conditions.

2-DE analysis of breast cancer cell lines 1833 and 4175 with distinct metastatic organ-specific potentials: comparison with parental cell line MDA-MB-231.

Human MDA-MB-231 derived breast cancer cell lines 1833 and 4175 have different metastatic potentials in terms of their tissue tropisms and aggressiveness. Cell line 1833 is specifically metastatic to the bone. The highly aggressive cell line 4175 is specific to the lung. We performed 2-DE analysis of the cell lines. We found 16 significantly changed protein spots, 14 protein spots were identified. Expression of cathepsin D, triosephosphate isomerase, phosphoglycerate kinase 1, heme binding protein 1 and annexin 2 could be correlated with the in vitro aggressiveness of the respective cell lines. Interstitial collagenase and dimethylargininase 2 were exclusive to the cell line 1833 and might contribute to its bone specificity. Serpin B9, cathepsin B chain b, galectin 3 and HSP 27 were changed in the lung specific cell line 4175. The possible contribution of identified proteins to differences in metastatic behavior of the cell lines is discussed.

The propeptide of cathepsin D increases proliferation, invasion and metastasis of breast cancer cells.

Expression and secretion of procathepsin D (pCD) increases proliferation, metastasis and progression of breast cancer but the structural moiety by which pCD exerts these effects is still ambiguous. Here, we present data on a series of pCD stable mutants to identify the pCD region that mediates this mitogenic effect. Mutations affecting the region of the activation peptide (AP) were studied together with catalytic and glycosylation mutants. Mitogenic effect was evaluated using in vitro invasion and proliferation assays and in vivo by determining the tumorigenic potential. The catalytic mutants and glycosylation mutants of pCD continued to display enhanced cell proliferation, invasion and tumorigenicity similar to stable transfectants of native pCD, suggesting that neither the proteolytic activity nor the sugar moieties contribute to the mitogenic effect. However, stable transfectants of pCD lacking its AP and with various mutations in the 27-44 amino acid region of AP, failed to show enhanced cell proliferation or invasion in vitro and tumor growth in vivo, establishing the importance of AP region. Our study concludes that the entire 27-44 amino acid region of AP is necessary for the stimulatory actions of pCD on breast cancer cells.

Depletion of procathepsin D gene expression by RNA interference: a potential therapeutic target for breast cancer.

Elevated level of procathepsin D (pCD), a zymogen of lysosomal aspartic proteinase cathepsin D, is associated with highly invasive neoplasms that include breast cancer. Independent studies have established that secreted pCD functions as a growth factor acting both in an autocrine and paracrine manner. Therefore, to explore whether pCD can be employed as a therapeutic target, the present study evaluates the impact of pCD knockdown using RNA interference technology. Of the three siRNA oligos tested, siRNA-3 exhibited a 90% inhibitory effect on pCD gene expression. Stable attenuation of pCD in breast cancer cells MDA-MB-231 was achieved by using a plasmid vector-based shRNA system. Pronounced suppression of pCD expression was accompanied by a significant reduction in invasion and proliferation of MDA-MB-231 cells stably transfected with functional shRNA. Importantly, in the athymic nude mice model, downregulation of pCD in breast cancer cells significantly reduced their metastatic potential. In addition, we observed a reduction in Cdc42 and NFkappaB2 expression in MDA-MB-231 cells with decreased pCD expression. When combined, our in vitro and in vivo experiments demonstrate that targeting pCD through RNAi technology represents a potential therapeutic tool for developing a therapy against breast cancer.

Procathepsin D secreted by HaCaT keratinocyte cells - A novel regulator of keratinocyte growth.

Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling.

Procathepsin D expression correlates with invasive and metastatic phenotype of MDA-MB-231 derived cell lines.

Procathepsin D (pCD) is a glycoprotein secreted abundantly by cancerous cells with a documented role in tumor development. The levels of pCD in primary tumors are highly correlated with an increased incidence of metastasis. Our earlier studies have shown that pCD exerts its effect on cancer cells through its activation peptide (AP) and involves both autocrine and paracrine modes of action. In this study, we analyzed the expression and role of pCD in MDA-MB-231 and its derived cell lines 1833 and 4175 possessing discrete metastatic abilities. Our results demonstrated a direct relationship between expression and secretion of pCD to the differential invasive potential of these cells. Also, the cell lines responded to AP treatment by enhancing their invasive potential, proliferation and induction of secretion of various cytokines, suggesting that pCD plays a role in metastasis through its AP region.

Secretion of cytokines in breast cancer cells: the molecular mechanism of procathepsin D proliferative effects.

Procathepsin D (pCD) is a major secreted protein in estrogen receptor-positive (ER+) breast cancer cell lines. Several independent studies have documented pronounced mitogenic effect of secreted pCD on cancer tissue-derived cell lines, including those from breast, lung, and prostate cancer. It has also been shown that the proliferative effect of pCD involves both autocrine and paracrine modes of action. Recent studies have suggested that pCD could act as a key paracrine communicator between cancer and stromal cells. We have shown earlier that the proliferative activity of pCD depends on the activation peptide sequence of pCD. The present study casts light on the mechanism by which pCD influences the proliferation of cancer cells expressing the ER. Results described in the current paper clearly show that pCD initiates secretion of cytokines interleukin-4 (IL-4), IL-8, IL-10, IL-13, macrophage inflammatory protein-1beta and (MIP-1beta) from such tumor cells. Secreted cytokines take part in the proliferation of the cancer cells, as proven by selective inhibition using antibodies. In addition, expression of cytokine receptors on tested cell lines corresponded to the effects of individual cytokines. An analogous pattern was also observed for fibroblasts, which, under physiologic conditions, are the cells in closest contact with the tumor tissue and play a role in tumor growth and invasion. Our observations were further supported by coculture experiments that are in agreement. Although very similar in response to addition of pCD, the invasive ER- cells do not secrete cytokines. Together with previous in vivo results, these data point to pCD as one of key molecules for therapeutic attack in breast cancer.

Ribozyme-targeting procathepsin D and its effect on invasion and growth of breast cancer cells: an implication in breast cancer therapy.

Procathepsin D (pCD), a zymogen of lysosomal aspartic peptidase cathepsin D, overexpression is correlated with highly invasive malignancies, including breast cancer. Recently, different studies have shown the role of secreted pCD as mitogen acting both in an autocrine and a paracrine manner. The aim of the present study is to examine the anti-tumor effects elicited by a decrease in the protein level of pCD by ribozyme and to explore the therapeutic potential of this specific targeting. Using the mFold program, we designed seven anti-pCD ribozymes and checked the accessibility to target pCD mRNA by RNase H cleavage experiment in a cell-free system. The sequences of the 4 most effective ribozymes were cloned and stably transfected in a highly metastatic human breast cancer cell line, MDA-MB-231, to knock down the expression of pCD. Downregulation of pCD due to ribozyme expression was observed by Western blotting and real-time RT-PCR. Stably transfected cells with anti-pCD ribozymes exhibited a significant lowering of in vitro invasion (p<0.001) and reduction in lung colonization potential in nude mice when compared to control ribozyme transfected cells. We also found that downregulation of pCD by ribozyme promotes apoptosis of MDA-MB-231 cells on serum deprivation. These results suggest that we have generated a biologically functional ribozyme against pCD with possible therapeutic implications in breast cancer cells.