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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.

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.

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.

Essential parts of rotating machineries are supporting nodes, i.e., bearing systems. They assure required rotational degrees of freedom and feature desired load carrying capacity. Following the specificity of a technical solution considered, various types of bearings may be taken into account to effectively address the requirements regarding the speed and load. Specifically, gas foil bearings (GFB) are used in high-speed and lightly-loaded rotating machineries, e.g., auxiliary power units. In fact, they can operate up to several hundreds of thousands rpm, also for a wide temperature range. The current work reports an application of piezoelectric composites to control operation of a GFB. The authors present the developed bearing’s prototype installation which is equipped with a specialized multifunctional structural component that advantageously allows to both characterize GFB’s operational parameters and modify them. The experimental results confirm the usability of the proposed actively-controlled configuration of a 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.

This paper focuses on a wear evaluation conducted for prototype spur and herringbone gears made from PET-G filament using additive manufacturing. The main objective of this study is to verify if 3D-printed gears can be considered a reliable choice for long-term exploitation in selected mechanical systems, specifically automated retail kiosks. For this reason, two methods were applied, utilizing: (1) vision-based inspection of the gears’ cross-sectional geometry and (2) the statistical characterization of the selected kinematic parameters and torques generated by drives. The former method involves destructive testing and allows for identification of the gears’ operation-induced geometric shape evolution, whereas the latter method focuses on searching for nondestructive kinematic and torque-based indicators, which allow tracking of the wear. The novel contribution presented in this paper is the conceptual and experimental application of the identification of the changes of 3D-printed parts’ geometric properties resulting from wear. The inspected exploited and non-exploited 3D-printed parts underwent encasing in resin and a curing process, followed by cutting in a specific plane to reveal the desired shapes, before finally being subjected to a vision-based geometric characterization. The authors have experimentally demonstrated, in real industrial conditions, on batch production parts, the usefulness of the presented destructive testing technique providing valid indices for wear identification.

An attempt was made to build a simple and low-cost device capable of positioning 3D prints for the process of additive manufacturing to conveniently allow the desired extend of the existing 3D printing capabilities. 3D printing with the use of increased number of axes, as compared to the standard approach, can eliminate such disadvantages of FDM technology as orthotropy of prints, surface roughness, and the consumption of both time and material devoted to make support structures. A CAD design of a parallel manipulator, used as a positioning table (platform), was developed, which was used for numerical simulations, and then a physical manipulator was made. The table was tested independently, i.e., as a stand-alone device, and, next, in cooperation with a 3D printer which allowed to obtain non-planar prints. The obtained results allowed for both the identification of problems related to multi-axis 3D FDM printing and an attempt to formulate concepts enabling to overcome them via adequate design and control modifications. The raised conclusions will be used to further development and more comprehensive understanding the phenomena that are present during the investigated manufacturing process.

The following content refers to the thermal aspects of Gas Foil Bearing (GFB). The GFBs are the subgroup of journal bearings, for which lubrication is provided by air, instead of ‘traditional’ lubricants like oil, graces etc. Gas Foil Bearings offer specific features unachievable for traditional bearings. GFB can operate with rotating speed up to several dozens of krpm in extreme temperature up to hundreds of Celsius degrees. However due to their specific construction, GFBs are prone to specific thermal issues which complicate their design process. Until now, many tools, mainly based on numerical models were developed. Their effectiveness is evaluated based on experimental data. Due to the high complexity of GFB’s structure, the temperature measurement is a challenging task and so far, no reliable simple technique was proposed. There is still a need for developing reliable measurement techniques, allowing for precise temperature measurement. This paper presents the novel approach to temperature measurement of the GFBs compliant structure. The unique concept of foil with integrated sensors was presented and described in detail.

Modern approaches dedicated to controlling the operation of gas foil bearings require advanced measurement techniques to comprehensively investigate the bearings’ thermal and thermomechanical properties. Their successful long-term maintenance with constant operational characteristics may be feasible only when the allowed thermal and mechanical regimes are rigorously kept. Hence, an adequate acquisition of experimental readings for the critical physical quantities should be conducted to track the actual condition of the bearing. The above-stated demand has motivated the authors of this present work to perform the thermomechanical characterization of the prototype installation of a gas foil bearing, applying a specialized sensing foil. This so-called top foil is a component of the structural part of the bearing’s supporting layer and composed of a superalloy, Inconel 625. The strain and temperature distributions were identified based on the readings from the strain gauges and integrated thermocouples mounted on the top foil. The measurements’ results were obtained for the experiments that represent the arbitrarily selected operational conditions of the tested bearing. Specifically, the considered measurement scenario relates to the operation at a nominal rotational speed, i.e., during the stable process, as well as to the run-up and run-out stages. The main objectives of the work are: (a) experimental proof for the described functionalities of the designed and manufactured specialized sensing foil that allow for the application of a novel approach to the bearing’s characterization, and (b) qualitative investigation of the relation between the mechanical and thermal properties of the tested bearing, using the measurements conducted with the newly proposed technical solution.

This article presents an experimental study carried out on a rotor operating on two foil bearings. One of the bearings was built in a way to measure the temperature and deformation of the top foil of the foil bearing. The dynamic performance of the two bearing journals is presented herein using the vibration trajectories and journal positions in the foil bearing sleeve. Based on these results, a method for predicting the temperature distribution on the top foil was developed. Then, the correlations between the temperature distribution and the operating parameters of the bearing journal were illustrated. It has been observed that the symmetry of the temperature distribution on the top foil depends on the eccentricity of the rotor operation. The shape and size of the vibration trajectory had no significant effect on the temperature value in the bearing, unlike the position of the journal in the bearing. The process of loss of the gas lubricating film was observed, which provides insight into the phenomena that occur during the first few seconds of rotor operation. The areas in the bearing from which fresh air had been drawn into the gap between the journal and the top foil were also determined.

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.

The work deals with the investigation of the variation of the selected 3D printing process properties that originate from the choice of a slicer. Specifically, the main aim of the present study was to assess the induced changes of the kinematic and geometric properties considered by the slicer for the printing process making use of the G-code readings. The paper provides adequate definitions and formulas required to characterize the slicer’s configuration. Next, the selected cases of the process parameters’ changes were studied, primarily taking into account varying layer height and infill. The authors performed a detailed analysis regarding the geometric implications at the mesoscale due to the slicer’s settings. Appropriate modifications of the slicer’s properties were also proposed and verified, making it possible to match the geometric and kinematic characteristics of the printed part.