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We develop a mesoscopic model to study the plastic behavior of an amorphous material under cyclic loading. The model is depinning-like and driven by a disordered thresholds dynamics that is coupled by long-range elastic interactions. We propose a simple protocol of “glass preparation” that allows us to mimic thermalization at high temperatures as well as aging at vanishing temperature. Various levels of glass stabilities (from brittle to ductile) can be achieved by tuning the aging duration. The aged glasses are then immersed into a quenched disorder landscape and serve as initial configurations for various protocols of mechanical loading by shearing. The dependence of the plastic behavior upon monotonous loading is recovered. The behavior under cyclic loading is studied for different ages and system sizes. The size and age dependence of the irreversibility transition is discussed. A thorough characterization of the disorder-landscape is achieved through the analysis of the transition graphs, which describe the plastic deformation pathways under athermal quasi-static shear. In particular, the analysis of the stability ranges of the strongly connected components of the transition graphs reveals the emergence of a phase-separation like process associated with the aging of the glass. Increasing the age and, hence, the stability ofmore »the initial glass results in a gradual break-up of the landscape of dynamically accessible stable states into three distinct regions: one region centered around the initially prepared glass phase and two additional regions characterized by well-separated ranges of positive and negative plastic strains, each of which is accessible only from the initial glass phase by passing through the stress peak in the forward and backward, respectively, shearing directions.

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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, and 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.

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 a 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.).