A detailed examination of the structure of the high-entropy alloy Al0.5CoCrCuFeNi at room temperature was carried out using different methods of optical microscopy, electron microscopy and X-ray structural analysis techniques. Numerical estimates of the dislocation density ∼5⋅1015 m−2, the mean size of the ordered (crystalline) domains ~18 nm and lattice micro strain ∼3⋅10−3 were obtained through Williamson-Hall analysis of XRD patterns. The estimates of the dislocation density were found to correlate with the estimates of the total length of dislocation segments per unit volume, which effectively interact with elastic vibrations of the sample ∼4⋅1013 m−2, as previously determined from acoustic relaxation measurements. This is consistent with the idea that a significant portion of dislocations are concentrated in grain boundaries, and only dislocation segments located inside grains and having a favourable orientation with respect to the direction of sound wave propagation can effectively interact with cyclic deformation of the sample.
This study investigates the mechanical behaviour and optimization of rigid flange couplings operating under two distinct environmental conditions: normal atmospheric air and high-pressure oil surroundings. A Taguchi L9 orthogonal array was employed to evaluate material combinations for the shaft, flange, and bolt based on four mechanical responses: total deformation, equivalent stress, shear stress, and normal stress. Analysis of variance (ANOVA) and regression modelling were used to identify significant parameters, with flange material consistently emerging as the most influential factor. Desirability analysis was conducted to determine the optimal material configurations for each environment. Under atmospheric conditions, the combination of C30 shaft, FG200 flange, and C45 bolt achieved a composite desirability of 0.6667. In high-pressure oil conditions, the optimal configuration was C45 shaft, FG260 flange, and C45 bolt, with a desirability of 0.7185. These optimal settings, not present in the original matrix, were independently validated using finite element analysis (FEA). The comparison between regression predictions and FEA results showed strong agreement, with a maximum percentage error of 6.02%, within acceptable engineering limits. This study confirms that environmental pressure significantly influences coupling performance and that material selection should be tailored accordingly. The integration of statistical optimization and simulation offers a robust framework for designing couplings in pressure-sensitive applications.
Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality, characterized by progressive airway and alveolar remodeling. The disease pathogenesis is commonly driven by chronic environmental insults, leading to airway obstruction, emphysema, and chronic bronchitis. This review synthesizes emerging evidence that altered epithelial cell behavior and dysfunctional epithelial-mesenchymal interactions serve as pivotal drivers of COPD pathogenesis, orchestrating failed repair and structural degeneration. We detail how altered responses of airway (ciliated, club, basal, goblet) and alveolar (AT1 and AT2) epithelial cells lead to cellular senescence, metaplasia, defective regeneration, and barrier disruption, acting as primary instigators of pathogenesis. We also summarize current knowledge on the mechanisms of activation and pathogenic role of mesenchymal cells, which drive peribronchiolar fibrosis, alveolar destruction, and metabolic reprogramming, alongside the compromised reparative function of mesenchymal stem cells (MSCs). We emphasize how distinct mesenchymal niches (e.g., PDGFRαPos MANCs, FGF10Pos lipofibroblasts, SFRP1Pos fibroblasts) and distinct epithelial stem/progenitor subpopulations critically contribute to pathogenesis. Key signaling pathways—including FGF10/FGFR2b, WNT, Hippo, NOTCH, and TGF-β—mediate epithelial-mesenchymal transition (EMT), stem cell niche function, and structural remodeling. By dissecting how epithelial injury responses and mesenchymal niche failure collaboratively drive COPD progression, we identify actionable targets to disrupt pathogenesis and restore endogenous repair. We propose targeting EMT, including inhibiting EMT/fibrosis, promoting alveolar regeneration, MSC-based therapies, exosome-delivered biomolecules, and precision cell transplantation strategies, as promising future therapeutic strategies.
CD8 T cells constitute one of the pillars of the adaptive immune response. They play a key role in eliminating pathogen-infected and cancerous cells. To effectively carry out their function, naïve CD8 T cells must undergo priming/activation in which several cell types, receptors, cytokines, and chemokines are involved. Various therapeutic approaches, such as vaccinations and anti-cancer therapies, i.e., immune checkpoint blockade (ICB) and Chimeric Antigen Receptor (CAR) T cell transfer, attempt to harness CD8 T cell biology to protect from or treat life-threatening diseases. Despite the significant success of CD8-T-cell-related therapies, the overall response rate of cancer patients remains relatively low, perhaps due to an incomplete understanding of the crucial events leading to optimal CD8 T cell activation. Recent findings highlight the importance of CD4 T cell help in CD8 T cell priming as well as the existence of an additional priming phase for the selection and expansion of high affinity T cells. Together, these findings offer a refined conceptual framework to guide future research and therapeutic development. Here, we present a revised perspective on clinically relevant CD8 T cell–based therapies in light of recent discoveries.
Patches of open water (polynyas) persist throughout six-month winters on many ice-covered lakes in boreal mountain ecoregions of northwestern North America. We explored their distribution, hydrological correlates, and the diversity of species using them from freeze-up to break-up. In headwater drainages, lakes with outflow polynyas were significantly larger than those without, but many small lakes also had polynyas. There was a consistent threshold in upstream catchment size below which outflow polynyas were absent and above which they persistently occurred in downstream lakes. Outflow polynyas depend on winter-long through-flow of water, likely maintained by the hydraulic head of higher elevation ground water in perched water tables in this region of very limited permafrost. Based on camera trapping, two species, the American dipper and river otter, used polynyas heavily throughout winter foraging. Polynyas likely provided crucial forage for at least 9 species of migratory waterfowl (Anatidae) to complete their spring migration or to prepare for reproduction on local lakes. Cameras recorded additional 5 bird and 11 mammal species, as foragers, scavengers, or incidentally. We report previously undocumented significance of these spatially-limited and seasonal polynya ecosystems in expanding the diversity of winter ecological opportunity for numerous species on small to medium-sized lakes.
