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            Dendritic cells (DCs), professional antigen-presenting cells, function as sentinels of the immune system. DCs initiate and fine-tune adaptive immune responses by presenting antigenic peptides to B and T lymphocytes to mount an effective immune response against cancer and pathogens. However, hypoxia, a condition characterized by low oxygen (O2-cryogels) tension in different tissues, significantly impacts DC functions, including antigen uptake, activation, and maturation, migration, as well as T-cell priming and proliferation. In this study, we employed O2-releasing biomaterials (O2-cryogels) to study the effect of localized O2 supply on human DC phenotype and functions. Our results indicate that O2-cryogels effectively mitigate DC exposure to hypoxia under hypoxic conditions. Additionally, O2--cryogels counteract hypoxia-induced inhibition of antigen uptake and migratory activity in DCs through O2-release and hyaluronic acid (HA) mediated mechanisms. Furthermore, O2-cryogels preserve and restore DC maturation and co-stimulation markers, including HLA-DR, CD86, and CD40, along with the secretion of proinflammatory cytokines in hypoxic conditions. Finally, our findings demonstrate that the supplemental O2-released from the cryogels preserves DC-mediated T-cell priming, ultimately leading to the activation and proliferation of allogeneic CD3+ T cells. This work emphasizes the potential of local oxygenation as a powerful immunomodulatory agent to improve DC activation and functions in hypoxia, offering new approaches for cancer and infectious disease treatments.more » « less
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            ABSTRACT The accepted gap—the time or distance a driver deems sufficient to enter or cross an intersection—is a key indicator of traffic risk, particularly at uncontrolled three‐legged intersections. Smaller accepted gaps are linked to higher risk due to an increased chance of vehicle conflicts. This study investigates the relationship between accepted gaps and risk and proposes a method to quantify the level of risk and severity (LORS) to guide targeted safety interventions. Data on vehicle speed, accepted gap and critical gap were collected from six rural intersections in India. Using a binary logit regression model and clustering techniques, the LORS was estimated and validated against actual accident data, yielding a predictive accuracy of up to 83%. The significance of this study lies in its novel data‐driven approach to safety assessment using parameters easily measured in the field. Designed for heterogeneous traffic conditions, the method provides traffic engineers and planners with a practical tool to assess intersection safety, recommend specific remedial measures and prioritise interventions based on risk and severity levels. With potential for automation and scalability, this research contributes to the development of safer road systems, particularly in low‐resource settings where conventional crash data is limited or unavailable.more » « lessFree, publicly-accessible full text available January 1, 2026
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            Abstract In oxygen (O2)‐controlled cell culture, an indispensable tool in biological research, it is presumed that the incubator setpoint equals the O2tension experienced by cells (i.e., pericellular O2). However, it is discovered that physioxic (5% O2) and hypoxic (1% O2) setpoints regularly induce anoxic (0% O2) pericellular tensions in both adherent and suspension cell cultures. Electron transport chain inhibition ablates this effect, indicating that cellular O2consumption is the driving factor. RNA‐seq analysis revealed that primary human hepatocytes cultured in physioxia experience ischemia‐reperfusion injury due to cellular O2consumption. A reaction‐diffusion model is developed to predict pericellular O2tension a priori, demonstrating that the effect of cellular O2consumption has the greatest impact in smaller volume culture vessels. By controlling pericellular O2tension in cell culture, it is found that hypoxia vs. anoxia induce distinct breast cancer transcriptomic and translational responses, including modulation of the hypoxia‐inducible factor (HIF) pathway and metabolic reprogramming. Collectively, these findings indicate that breast cancer cells respond non‐monotonically to low O2, suggesting that anoxic cell culture is not suitable for modeling hypoxia. Furthermore, it is shown that controlling atmospheric O2tension in cell culture incubators is insufficient to regulate O2in cell culture, thus introducing the concept of pericellular O2‐controlled cell culture.more » « less
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