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  1. Saleem, M. (Ed.)
    NKX3.1’s downregulation is strongly associated with prostate cancer (PCa) initiation, progression, and CRPC development. Nevertheless, a clear disagreement exists between NKX3.1 protein and mRNA levels in PCa tissues, indicating that its regulation at a post-translational level plays a vital role. This study identified a strong negative relationship between NKX3.1 and LIMK2, which is critical in CRPC pathogenesis. We identified that NKX3.1 degradation by direct phosphorylation by LIMK2 is crucial for promoting oncogenicity in CRPC cells and in vivo. LIMK2 also downregulates NKX3.1 mRNA levels. In return, NKX3.1 promotes LIMK2’s ubiquitylation. Thus, the negative crosstalk between LIMK2-NKX3.1 regulates AR, ARv7, andmore »AKT signaling, promoting aggressive phenotypes. We also provide a new link between NKX3.1 and PTEN, both of which are downregulated by LIMK2. PTEN loss is strongly linked with NKX3.1 downregulation. As NKX3.1 is a prostate-specific tumor suppressor, preserving its levels by LIMK2 inhibition provides a tremendous opportunity for developing targeted therapy in CRPC. Further, as NKX3.1 downregulates AR transcription and inhibits AKT signaling, restoring its levels by inhibiting LIMK2 is expected to be especially beneficial by co-targeting two driver pathways in tandem, a highly desirable requisite for developing effective PCa therapeutics.« less
  2. Free, publicly-accessible full text available October 1, 2023
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  4. Future tactical communications involves high data rate best effort traffic working alongside real-time traffic for time-critical applications with hard deadlines. Unavailable bandwidth and/or untimely responses may lead to undesired or even catastrophic outcomes. Ethernet-based communication systems are one of the major tactical network standards due to the higher bandwidth, better utilization, and ability to handle heterogeneous traffic. However, Ethernet suffers from inconsistent performance for jitter, latency and bandwidth under heavy loads. The emerging Time-Triggered Ethernet (TTE) solutions promise deterministic Ethernet performance, fault-tolerant topologies and real-time guarantees for critical traffic. In this paper we study the TTE protocol and build amore »TTTech TTE test bed to evaluate its performance. Through experimental study, the TTE protocol was observed to provide consistent high data rates for best effort messages, determinism with very low jitter for time-triggered messages, and fault-tolerance for minimal packet loss using redundant networking topologies. In addition, challenges were observed that presented a trade-off between the integration cycle and the synchronization overhead. It is concluded that TTE is a capable solution to support heterogeneous traffic in time-critical applications, such as aerospace systems (eg. airplanes, spacecraft, etc.), ground-based vehicles (eg. trains, buses, cars, etc), and cyber-physical systems (eg. smart-grids, IoT, etc.).« less
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