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Non-small cell lung cancer (NSCLC) is characterized by molecular heterogeneity with diverse immune cell infiltration patterns, which has been linked to therapy sensitivity and resistance. However, full understanding of how immune cell phenotypes vary across different patient subgroups is lacking. Here, we dissect the NSCLC tumor microenvironment at high resolution by integrating 1,283,972 single cells from 556 samples and 318 patients across 29 datasets, including our dataset capturing cells with low mRNA content. We stratify patients into immune-deserted, B cell, T cell, and myeloid cell subtypes. Using bulk samples with genomic and clinical information, we identify cellular components associated with tumor histology and genotypes. We then focus on the analysis of tissue-resident neutrophils (TRNs) and uncover distinct subpopulations that acquire new functional properties in the tissue microenvironment, providing evidence for the plasticity of TRNs. Finally, we show that a TRN-derived gene signature is associated with anti-programmed cell death ligand 1 (PD-L1) treatment failure.

Modelling and identification of the dynamic characteristics of foil bearings under varying loads pose a great challenge and require the use of advanced numerical models. Although simple models can represent the structural characteristics of foil bearings with a certain degree of approximation, they are not able to reliably predict the properties of such a system over a wide range of external and internal loads. This is why the authors of this paper have undertaken to develop a model of the foil bearing structure, which would take into account all the most important phenomena affecting its dynamic properties. The model was developed using the finite element method, making it possible to represent the complex shape of the foil assembly and its geometric nonlinearity as well as the contact phenomena and friction, using static and kinetic friction coefficients. This model was verified experimentally and then used to identify the dynamic characteristics of the foil bearing over a wide range of loads, including different radial clearance and assembly interference. An original method of modelling the assembly preload is also proposed. The results confirmed that the parameters analysed have an enormous impact on the stiffness and damping coefficients. The presented methods can help other researchers assess the dynamic characteristics of a bump-type foil bearing structure. The presented structural model provides dynamic parameters that are necessary for a thorough analysis of the entire foil bearing.

Interdigital transducers (IDTs), thanks to their multiple capabilities have the potential of increasing versatility of SHM systems. Migration of the IDT technology in SHM systems and devices is reviewed in this paper. A summary review of different types of IDTs is presented and their salient features are presented in terms of their applicability in the Lamb wave based SHM systems. Comprehensive review is provided concerning the implementation of the IDT capabilities towards the development of SHM systems. Experimental results obtained with prototype IDTs are provided for illustration. Finally, future development directions of the IDTs dedicated to SHM systems are outlined.

In this paper a novel concept of a tunable transducer for generation and sensing of the Lamb waves is presented. The proposed transducer is developed based on a commonly applied Interdigital Transducer (IDT). In the proposed design, further referred to as the Tunable IDT (T-IDT), the conventional comb electrodes with fixed pitch are replaced by a series of densely distributed discrete electrode strips. These electrodes can be easily interconnected in different configurations to match the required wavelength without a need of applying physical changes to the electrode layout. In order to verify the properties of the T-IDT, numerical simulations and experimental tests were performed and their results were compared to the ones obtained for the IDT. The outcomes from both the numerical and experimental analyses proved that the beampatterns generated by the T-IDT are similar to those determined for the conventional transducer. Moreover, the changes in electrode connections lead to the changes of phase-amplitude characteristics.

In this paper, universality of the mechatronic approach is confirmed with the examples of highly specialized and innovative systems, recently developed for a very specific applications. As shown, similar design steps, tools and testing procedures may lead to effective solutions even for distant and challenging research areas. First, an Ultralight Mobile Drilling System, dedicated to extraction of soil and rock probes from subsurface regions, is presented. For this case, minimization of mass and high mobility of the system, whilst maintaining performance of bigger drilling rigs, required during operation in space environment, is taken into account. The presented design consists of a four-wheeled rover with adjustable rocker mechanism, a multifunctional core drilling module and a support module with manipulation capabilities and dedicated sample storage. Second, entire design process for fully scalable and reconfigurable data-based system for monitoring of technical condition for mechanical constructions is introduced. The system is based on the measurements of electromechanical impedance, which are carried out with piezoelectric transducers. Both presented systems successfully passed the laboratory and industrial tests and, therefore, confirmed correctness of the choices made with the applied design procedures. All aspects of the mechatronic approach were investigated to construct fully functional prototypes designed for different tasks and to deal with different environmental conditions.

The past decades have been marked by a significant increase in research interest in nonlinearities in micro-cracked and cracked solids. As a result, a number of different nonlinear acoustic methods have been developed for damage detection. A general consensus is that – under favourable conditions – nonlinear effects exhibited by cracks are stronger than crack-induced linear phenomena. However, there is still limited understanding of physical mechanisms related to various nonlinearities. This problem remains essential for implementation of nonlinear acoustics for damage-detection applications. This paper reviews modelling approaches used for nonlinear crack–wave interactions. Various models of classical and nonclassical crack-induced elastic, thermo-elastic and dissipative nonlinearities have been discussed.

This paper addresses the robustness analysis of modal characteristics of an undamped FE windscreen model subjected to geometrical variability. The studied acoustic windscreen is a sandwich structure composed of five different layers. Assuming the thickness of these layers are affected by irreducible uncertainty, this research aims to investigate the effect such uncertainty has on the eigenvalues and eigenvectors dispersion corresponding to different nominal configurations. The analysis is carried out via response surface methodology coupled with Monte Carlo simulation. Response surface methodology is in charge of building meta-models, which approximate both natural frequencies and mode shapes. Once the response surface approximations are constructed, Monte Carlo simulations can be performed using the meta-models to quickly propagate the input parameters variability. Finally, the analysis of the Monte Carlo outputs allows one to infer the robustness of the dynamic response of the system.

Engineering tools which are currently available within the realm of virtual prototyping allow for the assessment of variation of mechanical structure properties. This goal can be achieved through the application of uncertainty analysis. Both probabilistic and possibilistic approaches are employed for studying uncertainty propagation in FE models. Numerical simulations enable shortening time-to-market for designed mechanical systems. However, great number of iterations required in non-deterministic analyses may dramatically reduce the scope of possible applications, especially in respect of time-consuming dynamic analyses. In the dissertation, the effective CFGA method is proposed to assess the variations of natural frequencies of FE model. Briefly, the advantages of the method include reduced number of eigenproblems to solve in dynamic analyses and relatively high quality of results. Hence the significant reduction of computational time. It is of a great importance, especially in the case when a large number of degrees of freedom are considered in an FE model and, as a consequence, a solution of dynamic problem is very time-consuming. The paper includes selected application of described method.

Given the simplicity of the DNA sequence that mediates binding of GATA transcription factors, GATA motifs reside throughout chromosomal DNA. However, chromatin immunoprecipitation analysis has revealed that GATA-1 discriminates exquisitely among these sites. GATA-2 selectively occupies the -2.8-kilobase (kb) region of the GATA-2 locus in the active state despite there being numerous GATA motifs throughout the locus. The GATA-1-mediated displacement of GATA-2 is tightly coupled to repression of GATA-2 transcription. We have used high resolution chromatin immunoprecipitation to show that GATA-1 and GATA-2 occupy two additional regions, -3.9 and -1.8 kb of the GATA-2 locus. GATA-1 and GATA-2 had distinct preferences for occupancy at these regions, with GATA-1 and GATA-2 occupancy highest at the -3.9- and -1.8-kb regions, respectively. Activation of an estrogen receptor fusion to GATA-1 (ER-GATA-1) induced similar kinetics of ER-GATA-1 occupancy and GATA-2 displacement at the sites. In the transcriptionally active state, DNase I hypersensitive sites (HSs) were detected at the -3.9- and -1.8-kb regions, with a weak HS at the -2.8-kb region. Whereas ER-GATA-1-instigated repression abolished the -1.8-kb HS, the -3.9-kb HS persisted in the repressed state. Transient transfection analysis provided evidence that the -3.9-kb region functions distinctly from the -2.8- and -1.8-kb regions. We propose that GATA-2 transcription is regulated via the collective actions of complexes assembled at the -2.8- and -1.8-kb regions, which share similar properties, and through a qualitatively distinct activity of the -3.9-kb complex.