Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.
The paper focused on the seismic performance of ceramsite concrete frame—shear wall, which conducted the modal analysis and elasto-plastic time history analysis for 6 layers ceramsite concrete frame—shear wall and ordinary concrete frame—shear wall by software SAP2000. Then compared the results, which showed that the periods of ceramsite concrete frame—shear wall structure was longer than the ordinary concrete frame—shear wall structure, while the inter-storey drift ratio and the maximum absolute acceleration are less than ordinary concrete frame—shear wall. Besides, the largest base shear of ceramsite concrete frame—shear wall structure was less than ordinary concrete frame—shear wall structure. And the seismic performance of ceramsite concrete frame—shear wall showed was better than ordinary concrete frame—shear wall structure.
Working principle of an uninterrupted shift transmission (UST) based on overrunning mechanism and its driveline dynamic model, as well as shift control strategy are studied. For shift quality optimization, the throttle control parameters are calculated based on simplex method and genetic algorithm. Using the control strategy and optimized parameters, simulation results show that jerks and clutch slip during shift are controlled well, satisfactory shift quality is obtained without power flow interruption.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.