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Lutu, Andra; Zhang, Ying (Ed.)Design for low latency networking is essential for tomorrow’s interactive applications, but it is essential to deploy incrementally and universally at the network’s last mile. While wired broadband ISPs are rolling out the leading queue occupancy signaling mechanisms, the cellular Radio Access Network (RAN), another important last mile to many users, lags behind these efforts. This paper proposes a new RAN design, L4Span, that abstracts the complexities of RAN queueing in a simple interface, thus tying the queue state of the RAN to end-to-end low-latency signaling all the way back to the content server. At millisecond-level timescales, L4Span predicts the RAN’s queuing occupancy and performs ECN marking for both low-latency and classic flows. L4Span is lightweight, requiring minimal RAN modifications, and remains 3GPP and O-RAN compliant for maximum ease of deployment. We implement a prototype on the srsRAN open-source software in C++. Our evaluation compares the performance of low-latency as well as classic flows with or without the deployment of L4Span in various wireless channel conditions. Results show that L4Span reduces the one-way delay of both low-latency and classic flows by up to 98%, while simultaneously maintaining near line-rate throughput.more » « lessFree, publicly-accessible full text available December 1, 2026
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Zhang, Ying (Ed.)ABSTRACT Treponema pallidum, the causative agent of syphilis, poses a significant global health threat. Its strict reliance on host-derived nutrients and difficulties inin vitrocultivation have impeded detailed metabolic characterization. In this study, we present iTP251, the first genome-scale metabolic model ofT. pallidum, reconstructed and extensively curated to capture its unique metabolic features. These refinements included the curation of key reactions such as pyrophosphate-dependent phosphorylation and pathways for nucleotide synthesis, amino acid synthesis, and cofactor metabolism. The model demonstrated high predictive accuracy, validated by a MEMOTE score of 92%. To further enhance its predictive capabilities, we developed ec-iTP251, an enzyme-constrained version of iTP251, incorporating enzyme turnover rate and molecular weight information for all reactions having gene-protein-reaction associations. Ec-iTP251 provides detailed insights into protein allocation across carbon sources, showing strong agreement with proteomics data (Pearson’s correlation of 0.88) in the central carbon pathway. Moreover, the thermodynamic analysis revealed that lactate uptake serves as an additional ATP-generating strategy to utilize unused proteomes, albeit at the cost of reducing the driving force of the central carbon pathway by 27%. Subsequent analysis identified glycerol-3-phosphate dehydrogenase as an alternative electron sink, compensating for the absence of a conventional electron transport chain while maintaining cellular redox balance. These findings highlightT. pallidum’s metabolic adaptations for survival and redox balance in nutrient-limited, extracellular host environments, providing a foundation for future research into its unique bioenergetics. IMPORTANCEThis study advances our understanding ofTreponema pallidum, the syphilis-causing pathogen, through the reconstruction of iTP251, the first genome-scale metabolic model for this organism, and its enzyme-constrained version, ec-iTP251. The work addresses the challenges of studyingT. pallidum, an extracellular, host-adapted pathogen, due to its strict dependence on host-derived nutrients and challenges inin vitrocultivation. Validated with strong agreement to proteomics data, the model demonstrates high predictive reliability. Key insights include unique metabolic adaptations such as lactate uptake for ATP production and alternative redox-balancing mechanisms. These findings provide a robust framework for future studies aimed at unraveling the pathogen's survival strategies and identifying potential metabolic vulnerabilities.more » « lessFree, publicly-accessible full text available May 20, 2026
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