Multi-omics profiles refine L-dopa decarboxylase (DDC) as a reliable biomarker for prognosis and immune microenvironment of clear cell renal cell carcinoma

BackgroundIncreasing evidence indicates that L-dopa decarboxylase (DDC), which mediates aberrant amino acid metabolism, is significantly associated with tumor progression. However, the impacts of DDC are not elucidated clearly in clear cell renal cell carcinoma (ccRCC). This study aimed to evaluate DDC prognostic value and potential mechanisms for ccRCC patients.MethodsTranscriptomic and proteomic expressions of and clinical data including 532 patients with ccRCC (The Cancer Genome Atlas RNA-seq data), 226 ccRCC samples (Gene Expression Omnibus), 101 ccRCC patients from the E-MTAB-1980 cohort, and 232 patients with ccRCC with proteogenomic data (Fudan University Shanghai Cancer Center) were downloaded and analyzed to investigate the prognostic implications of DDC expression. Cox regression analyses were implemented to explore the effect of DDC expression on the prognosis of pan-cancer. The "limma" package identified the differentially expressed genes (DEGs) between high DDC subgroups and low DDC groups. Functional enrichments were performed based DEGs between DDC subgroups. The differences of immune cell infiltrations and immune checkpoint genes between DDC subgroups were analyzed to identify potential influence on immune microenvironment.ResultsWe found significantly decreased DDC expression in ccRCC tissues compared with normal tissues from multiple independent cohorts based on multi-omics data. We also found that DDC expression was correlated with tumor grades and stages.The following findings revealed that lower DDC expression levels significantly correlated with shorter overall survival (P <0.001) of patients with ccRCC. Moreover, we found that DDC expression significantly correlated with an immunosuppressive tumor microenvironment, higher intra-tumoral heterogeneity, elevated expression of immune checkpoint CD274, and possibly mediated malignant behaviors of ccRCC cells via the PI3k/Akt signaling pathway.ConclusionThe present study is the first to our knowledge to indicate that decreased DDC expression is significantly associated with poor survival and an immune-suppressive tumor microenvironment in ccRCC. These findings suggest that DDC could serve as a biomarker for guiding molecular diagnosis and facilitating the development of novel individual therapeutic strategies for patients with advanced ccRCC

FEM analysis to the slab corner metal flow condition during multi-pass V-H rolling process

The multi-pass vertical-horizontal (V-H) rolling process using plain-barreled edging roll and two grooved edging rolls with inward chamfer radius R=50 mm and R=80 mm was modeled by way of explicit dynamic FEM and updated geometries, and the slab corner metal flow under the conditions as above was analyzed. With the specified rolling schedule, it was found that the slab corner metal is curling and overturning onto the slab top surface when using the plain-barreled edging roll, and the slab corner metal is kept onto the line intersecting the top surface with side surface of the slab when using grooved edging roll

Influence of groove fillet radii of edger roll on slab deformation

The V-H(vertical-horizontal) rolling process with groove fillet radii of vertical roll R of 30, 50, 80, 110 mm was simulated by explicit dynamic FEM. The influences of groove fillet radii of vertical rolls on cropping and margin deformation of slab were analyzed. The results show that during the first V-H rolling pass, the non-uniform region length of slab head and tail is decreased as the fillet radius is reduced; during the second and third passes, the pass increment of non-uniform region length of slab is decreased as the fillet radius is increased; comparing of the non-uniform region length with V-roll R 30 mm and V-roll R 110 mm, the former is 5.03% less than the later; the deformation degree of stable segment is reduced as the fillet radius is increased

Research on behavior of slab surface defects in forward slip zone during V-H rolling process

Behavior of the transversal crack and the longitudinal crack on slab surface during V-H rolling was simulated by the FEM. The contact pressure on crack surfaces and the crack-tip stress change rules during rolling were analyzed. Results show that the contact pressure on crack surfaces decreases and the tensile stress appears at crack tip in the zone of slippage on the delivery side, which may make the cracks propagation. For the phenomenon, the stress distribution along rolling direction and along width direction in rolling are analyzed, and the influence of forward slip on the closure and growth of the surface transversal crack and the surface longitudinal crack are discussed. Results support some significant information for researching the behavior of the slab surface defects in rolling process

Research on the corner stress of dog-bone shaped workpiece during flat-spread rolling

FEM simulation was done for the deformation behavior of a dog-bone shaped workpiece during flat-spread rolling. The effects of the apical position and maximum height of the workpiece and pass reductions on its corner tensile stress in rolling process were analyzed. The results showed that the change in apical position affects greatly the corner tensile stress which can be increased by 66.7%, and the changes in maximum height and pass reduction affect the corner tensile stress rather smaller. The comer tensile stress increases with the positional distance of the workpiece. The conclusion drawn from the simulation is of significance to improving productivity especially the rate of finished products

Suggestions for Criteria to Evaluate Lateral-Directional Nonlinear Pilot-Induced Oscillations Due to Fly-by-Wire Civil Aircraft Landing Configuration Switch

Using a nonlinear pilot-induced oscillation prediction method based on digital virtual flight simulation calculations, digital experiments on predicting lateral-directional nonlinear pilot-induced oscillations due to landing configuration switching of fly-by-wire civil aircraft with different closed-loop dynamic characteristics are carried out. It is proposed that the lateral-directional pilot-induced oscillations due to the landing configuration switch can be evaluated using the changes in dynamic characteristic parameters before and after the configuration switch. The quantitative boundaries of the dynamic characteristic parameters of an example aircraft are determined, and a criterion suggestion is formed to predict the lateral-directional nonlinear pilot-induced oscillations due to landing configuration switching. This study provides a reference for the optimal design of the lateral-directional flight control law of fly-by-wire aircraft during the approach stage and provides suggestions for the formulation of evaluation criteria for other nonlinear pilot-induced oscillation phenomena