Abstract. Membrane-cytoskeleton linker organizer ezrin is a member of the ERM (ezrin-radixin-moesin) protein family. It has been suggested as an important element in the oncogenic process, particularly in conferring a metastatic ability on tumor cells. We hypothesized that the KIT oncogenic form is one of the proteins that modulates expression of the ezrin protein via phosphorylated ezrin at different residues; furthermore, it may interact with the protein merlin, and promoting tumor development via the PI3K or MAPK pathway. In the present study, we observed that differential expression of ezrin was a common feature in gastrointestinal stromal tumors (GISTs). We further demonstrated that cases exhibiting expression of phosphorylated Thr567 in the ezrin protein were associated with immunoactivities of KIT and merlin expression (p=0.039 and 0.013, respectively). In conclusion, GISTs harbor activation of KIT protein may induce phosphorylation of the downstream protein ezrin at certain residues, thereby triggering subsequent signal transduction cascades and driving downstream pathways of tumor progression. However, a larger series of tumor samples should be analyzed in future studies, as well as the identification of phosphorylated sites to determine the role of ezrin in tumor progression thus shedding light on clinical outcomes.
Ever-tightened design rules and ensuing aggressive OPC features pose significant challenges for wafer fabs in the pursuit of compelling yield and productivity. The introduction of advanced reticles considerably augments the mask error enhancement factor (MEEF) where progressive defects or haze, induced by repeated laser exposure, continue to be a source of reticle degradation threatening device yield. High resolution reticle inspection now emerges as a rescue venue for wafer fabs to assure their photomask integrity during intensive deep UV exposure. Integrated in the high resolution reticle inspection, a MEEF-driven lithographic detector "Litho3" can be used run-time to group critical defects into a single bin. Previous investigations evinced that critical defects identified by such detector were directly correlated with defects printed on wafer, upon which fab users can make cogent decisions towards reticle disposition and cleaning therefore reduce cycle time.One of the challenges of implementing such detector resides in the lengthy set up of user-defined parameters, from practitioner standpoint, can considerably extend reticle inspection time and inevitably delay production. To overcome this, an automatic simulation program has been written to optimize Litho3 settings based off a pre-inspection in which only default Litho3 values are needed. Upon completion of the pre-inspection, the images are then scanned and processed to extract the optimal Litho3 parameters that are largely dependent upon the feature size characteristics and local MEEF. Thus optimized Litho3 parameters can then be input into the recipe set up to enable a real-time inspection, as such fab user can timely access the defect criticality information for subsequent defect disposition. In the interest of printability validation, such defect information and associated coordinates can be passed onto defect review via XLINK for further analysis. Corresponding MEEF values are also available for all identified critical defects. Through this automatic program the set up time for Litho3 can be reduced by up to 90%.For high capacity production fabs running a pre-inspection is deemed infeasible; this automatic optimization program can also serve as a direct interpretation of any regular reticle inspection even without invoking Litho3 set up, yet in the end provide output in the context of defect criticality. Results acquired from this program were found in good accordance with those from the real-time Litho3 inspection, for both critical and non-critical layers of 90 nm design node. Such capability allows detailed study of defect criticality in relation to its size, defect optical transmittance, residing surface, its proximity to a printing pattern as well as lithography parameters such as NA and sigma. Furthermore, coupling this automatic program with high resolution inspection also assists in determining lithography process window and an indepth comprehension of defect progression mechanism.
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