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null (Ed.)Cell-cell interaction is critical for tissue development and repair, immunological responses, and cancer cell metastasis. The tyrosine kinase EPHA3 (erythropoietin‑producing hepatocellular carcinoma cell surface type-A receptor 3) regulates cell-cell interaction, cell differentiation, and cancer cell survival. Previously, our published study indicated that the theSTK4-encoded MST1 signaling, a core kinase component of the Hippo pathway, suppressedEPHA3 expression in the prostate cancer cell models. However, the mechanism is unknown. Here, we have demonstrated that the YAP1 and TEAD1 proteins, critical nuclear effectors of the Hippo pathway, mediate EPHA3 expression. First, we showed that AR-positive cell lines express the highest levels of EPHA3 and its ligand, ephrin-A5, transcripts compared with other EPH family members. Second, we demonstrated the induction of MST1/STK4attenuated the EPHA3 protein and transcripts, consistent with our initial observation. Next, we demonstrated that the knockdown of YAP1 by siRNA suppressed EPHA3 protein and mRNA expression. Similarly, the silencing of the TEAD1-4 proteins, critical mediators of YAP1-dependent gene transcription, revealed that the TEAD1 is a crucial inducer of EPHA3expression. Moreover, bioinformatics tools allowed the identification of three putative TEAD binding sites (p<0.001) in the promoter region of the EPHA3 gene. Furthermore, CRISPR/Cas9-aided EPHA3 knockout significantly (p<0.01), decreased cell growth in monolayer and sphere formation in 3D cultures, and caused androgen-independent cells to become sensitive to enzalutamide, a potent direct inhibitor of AR activity. These observations suggest that the YAP/TEAD1 transcriptionally regulates EPHA3 and its cellular biology.more » « less
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We design and implement a fully concurrent dynamic hash table for GPUs with comparable performance to the state of the art static hash tables. We propose a warp-cooperative work sharing strategy that reduces branch divergence and provides an efficient alternative to the tradi- tional way of per-thread (or per-warp) work assignment and processing. By using this strategy, we build a dynamic non- blocking concurrent linked list, the slab list, that supports asynchronous, concurrent updates (insertions and deletions) as well as search queries. We use the slab list to implement a dynamic hash table with chaining (the slab hash). On an NVIDIA Tesla K40c GPU, the slab hash performs updates with up to 512 M updates/s and processes search queries with up to 937 M queries/s. We also design a warp-synchronous dynamic memory allocator, SlabAlloc, that suits the high performance needs of the slab hash. SlabAlloc dynamically allocates memory at a rate of 600 M allocations/s, which is up to 37x faster than alternative methods in similar scenarios.more » « less
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We develop a dynamic dictionary data structure for the GPU, supporting fast insertions and deletions, based on the Log Structured Merge tree (LSM). Our implementation on an NVIDIA K40c GPU has an average update (insertion or deletion) rate of 225 M elements/s, 13.5x faster than merging items into a sorted array. The GPU LSM supports the retrieval operations of lookup, count, and range query operations with an average rate of 75 M, 32 M and 23 M queries/s respectively. The trade-off for the dynamic updates is that the sorted array is almost twice as fast on retrievals. We believe that our GPU LSM is the first dynamic general-purpose dictionary data structure for the GPU.more » « less