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Mechanical properties of the components of a pantograph’s slider suspension system have large influence on the quality of pantograph-catenary interaction. In the paper the authors present the results of their experimental research on the springs that are used in the pantograph being currently in operation in Europe. Static and dynamic tests were performed, which were aimed at determining the stiffness and damping coefficients respectively. Subsequently, the procedure for automated numerical model building for the pantograph’s springs was prepared employing the Python programming language and the MSC Marc solver. When a spring model is build (accordingly to the geometric properties of the springs used in tests), the elaborated algorithm iteratively tunes the material properties and computes static and dynamic load-cases, making direct reference to the experimental procedure. After completing several iterations the numerical model is finally validated, and proper material properties, as the Young modulus and the coefficients of Rayleigh damping model, are found. Then, the obtained model can be used to determine the damping and stiffness coefficients for springs characterizing various diameters, wire diameters, numbers of turns, etc. The presented modelling tool is useful for determining the pantograph sliders suspension characteristics.

Abstract Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.

There is a need for modelling various phenomena present in a pantograph-catenary structure, (e.g. wave propagation and its reflections, friction, aerodynamic and electromagnetic forces), which allows for a more reliable study on the dynamic behaviours of a railway pantograph, particularly in the case of high-speed trains. Hence, the creation a complex pantograph-catenary multi-domain model should help to effectively meet the above-mentioned requirements. The work presents a co-simulation approach to investigate the pantograph-catenary dynamic interaction. The elaborated co-simulation algorithm assumes data exchange between multibody models of a pantograph and finite element model of a catenary. The presented approach explores multi-domain phenomena that have an influence on the pantograph-catenary interaction. The nonlinear finite element catenary model takes into account the slackening of droppers, relatively large displacements and contact with the pantograph’s slider, while the multibody model of the pantograph considers friction forces and suspension springs. Additionally, aerodynamic forces caused by wind acting on the pantograph were computed using the fluid structure interaction method and implemented in the dynamic simulation. The influence on the pantograph-catenary interaction caused by electromagnetic force acting on the pantograph was investigated, along with the influence of the locomotive’s vertical vibrations and tilt.

Relatively recent discovery of shape memory alloys (SMA) justifies ongoing research on their properties and an attempt to explain the physical phenomenon responsible for the characteristic behaviour of SMA. Moreover, there have been reported many successful commercial SMA applications to medical cases, mostly based on superelasticity. Even though a wide application range is confirmed, its further contribution growth is currently not seen - mostly due to deficiency of reliable modelling techniques. Recently, lively discussion in the SMA academic community is observed, which deals with modelling issues and numerical implementation. Considering the current trends, the authors of the work make an attempt at qualitative analysis of the material properties for superelasticity. The material characteristics – found using static stretching tests – are sensitive to the variation of local stresses induced in the area where a SMA sample is mounted in a fatigue testing machine. As shown, the phenomena present at the clamping area seem to initiate and govern the process of the solid phase transformation within the entire SMA body. The overall objective of the presented research is to assess the influence of the above stated boundary conditions on the properties of selected types of SMA, using both experimental and numerical results.

The development of single-cell omics tools has enabled scientists to study the tumor microenvironment (TME) in unprecedented detail. However, each of the different techniques may have its unique strengths and limitations. Here we directly compared two commercially available high-throughput single-cell RNA sequencing (scRNA-seq) technologies - droplet-based 10X Chromium vs. microwell-based BD Rhapsody - using paired samples from patients with localized prostate cancer (PCa) undergoing a radical prostatectomy.Although high technical consistency was observed in unraveling the whole transcriptome, the relative abundance of cell populations differed. Cells with low mRNA content such as T cells were underrepresented in the droplet-based system, at least partly due to lower RNA capture rates. In contrast, microwell-based scRNA-seq recovered less cells of epithelial origin. Moreover, we discovered platform-dependent variabilities in mRNA quantification and cell-type marker annotation. Overall, our study provides important information for selection of the appropriate scRNA-seq platform and for the interpretation of published results.

The paper describes the results of a study aimed at identifying the mechanical parameters of a prosthetic foot designed for wall climbing. The prosthesis was manufactured with an additive method using FDM/MEX [Fused Deposition Modelling/ Material Extrusion] technology. At the initial stage of the research, uniaxial tensile and three-point bending tests were carried out on specimens made of six different materials to select a material for the production of the prosthetic component. Based on the results, a functional prosthetic foot prototype was designed and fabricated from two selected polymers. The final step of the study was to subject the prosthesis to a cyclic bending test on a dynamic testing machine equipped with a newly-designed adapter. The functionality of the fabricated component was also confirmed on a climbing wall, under controlled conditions of use. Based on the tests and analysis conducted, it was concluded that the created prosthesis fulfills its purpose and provides more comfort during climbing than an everyday prosthesis, while keeping the production cost low. Keywords: mechanical engineering, additive manufacturing, 3D printing, prosthetic foot, prosthesis, climbing

Abstract Background The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. Methods For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAMhigh breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAMlow breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. Results In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAMhigh cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAMlow cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. Conclusions The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer.

Abstract Background Recently, EpCAM has attracted major interest as a target for antibody- and vaccine-based cancer immunotherapies. In breast cancer, the EpCAM antigen is overexpressed in 30-40% of all cases and this increased expression correlates with poor prognosis. The use of EpCAM-specific monoclonal antibodies is a promising treatment approach in these patients. Methods In order to explore molecular changes following EpCAM overexpression, we investigated changes of the transcriptome upon EpCAM gene expression in commercially available human breast cancer cells lines Hs578T and MDA-MB-231. To assess cell proliferation, a tetrazolium salt based assay was performed. A TCF/LEF Reporter Kit was used to measure the transcriptional activity of the Wnt/β-catenin pathway. To evaluate the accumulation of β-catenin in the nucleus, a subcellular fractionation assay was performed. Results For the first time we could show that expression profiling data of EpCAM transfected cell lines Hs578TEpCAM and MDA-MB-231EpCAM indicate an association of EpCAM overexpression with the downregulation of the Wnt signaling inhibitors SFRP1 and TCF7L2. Confirmation of increased Wnt signaling was provided by a TCF/LEF reporter kit and by the finding of the nuclear accumulation of ß-catenin for MDA-MB-231EpCAM but not Hs578TEpCAM cells. In Hs578T cells, an increase of proliferation and chemosensitivity to Docetaxel was associated with EpCAM overexpression. Conclusions These data show a cell type dependent modification of Wnt signaling components after EpCAM overexpression in breast cancer cell lines, which results in marginal functional changes. Further investigations on the interaction of EpCAM with SFRP1 and TCF7L2 and on additional factors, which may be causal for changes upon EpCAM overexpression, will help to characterize unique molecular properties of EpCAM-positive breast cancer cells.

Abstract Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

Bearings are commonly employed in various types of rotating machineries. Their properties indisputably influence the overall performance and time of maintenance-free operation of the mechanical systems in which they are used to support the shafts. Consequently, much effort is considered to provide reliable bearings’ solution and develop new methods and technical tools for measurement and possibly modification of the operational characteristics of the above-mentioned parts. In reference, the concept of a smart bearing is developed as providing the means for real-time passive and active control of the bearings’ behavior as well as different types of smart materials are used to enhance their characteristics. The current study deals with an applications of structural components made of shape memory alloys to gas foil bearings (GFB). The paper presents and discusses the results of experimental tests conducted for the bearing’s prototype to characterize the efficiency of thermally-induced modifications of geometric properties of one of the crucial parts of the investigated GFB.

Over the last decade, a constantly growing trend of the popularization of self-service automated stores has been observed. Vending machines have been expanded into fully automated stores, the offer of which is comparable to small, conventional stores. One of the basic reasons for the popularization of modern automated stores is the reduction in a store’s energy consumption while ensuring a comparable range of products offered. The research into possibilities of reducing greenhouse gases emission is important in terms of the environment and climate protection. The research presented in the paper concerns the development of a model for determining electricity consumption, operating costs and CO2 emission of an automated store designed and developed by Delfin company. In the developed model, the potential location of the store, prevailing climatic conditions and expected product sales are taken into account. Estimated energy demand for the store is the information of key importance for the potential investors and the manufacturer of the automated store. It is worth emphasizing that the average annual electrical energy consumption evaluated for a grocery store of an area of 70 m2 amounted to approximately 38.4 MWh, while for an automated store of an area of 9 m2 and a comparable product range, the electricity consumption was approximately 10.1 MWh, i.e., 74% smaller.

Renal cell carcinoma (RCC) is frequently infiltrated by immune cells, a process which is governed by chemokines. CD8+ T cells in the RCC tumor microenvironment (TME) may be exhausted which most likely influence therapy response and survival. The aim of this study was to evaluate chemokine-driven T cell recruitment, T cell exhaustion in the RCC TME, as well as metabolic processes leading to their functional anergy in RCC. Eight publicly available bulk RCC transcriptome collectives (n=1819) and a single cell RNAseq dataset (n=12) were analyzed. Immunodeconvolution, semi-supervised clustering, gene set variation analysis and Monte Carlo-based modeling of metabolic reaction activity were employed. Among 28 chemokine genes available, CXCL9/10/11/CXCR3, CXCL13/CXCR5 and XCL1/XCR1 mRNA expression were significantly increased in RCC compared to normal kidney tissue and also strongly associated with tumor-infiltrating effector memory and central memory CD8+ T cells in all investigated collectives. M1 TAMs, T cells, NK cells as well as tumor cells were identified as the major sources of these chemokines, whereas T cells, B cells and dendritic cells were found to predominantly express the cognate receptors. The cluster of RCCs characterized by high chemokine expression and high CD8+ T cell infiltration displayed a strong activation of IFN/JAK/STAT signaling with elevated expression of multiple T cell exhaustion-associated transcripts. Chemokinehigh RCCs were characterized by metabolic reprogramming, in particular by downregulated OXPHOS and increased IDO1-mediated tryptophan degradation. None of the investigated chemokine genes was significantly associated with survival or response to immunotherapy. We propose a chemokine network that mediates CD8+ T cell recruitment and identify T cell exhaustion, altered energy metabolism and high IDO1 activity as key mechanisms of their suppression. Concomitant targeting of exhaustion pathways and metabolism may pose an effective approach to RCC therapy.

Maintenance of adequate thermal properties is critical for correct operation of a gas foil bearing. In this work, the authors present the results of the experimentally conducted thermal characterization of a prototype installation of the bearing. A novel method of temperature identification, based on integrated thermocouples readings, has been employed to determine the thermal properties of the specialized sensing top foil mounted in the tested bearing. Two measurement campaigns have been subsequently completed, applying freely-suspended and two-node support configurations, to gather complementary knowledge regarding the bearing’s operation. Apart from the rotational speed and temperature field measurements, the authors have also studied the friction torque and the shaft’s journal trajectories based on its radial displacements. The temporal courses for the above-mentioned quantities have enabled inference on the effects present during run-up, run-out and stable state operation at a constant speed. As confirmed, the applied distribution of the integrated sensors allows for temperature readings on the entire outer surface of the foil, and therefore, provides useful data for the bearing characterization. The work is concluded with presentation of the recommended directions regarding future improvements of the proposed measurement technique and more comprehensive study of the bearing’s characteristics.