Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes

BackgroundProinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In the current study, we sought to investigate the prognostic value of TLS-associated chemokines/cytokines (TLS-kines) expression levels in melanoma patients by performing serum protein and tissue transcriptomic analyses, and to then correlate these data with patients clinicopathological and TME characteristics.MethodsLevels of TLS-kines in patients’ sera were quantitated using a custom Luminex Multiplex Assay. The Cancer Genomic Atlas melanoma cohort (TCGA-SKCM) and a Moffitt Melanoma cohort were used for tissue transcriptomic analyses. Associations between target analytes and survival outcomes, clinicopathological variables, and correlations between TLS-kines were statistically analyzed.ResultsSerum of 95 patients with melanoma were evaluated; 48 (50%) female, median age of 63, IQR 51-70 years. Serum levels of APRIL/TNFSF13 were positively correlated with levels of both CXCL10 and CXCL13. In multivariate analyses, high levels of serum APRIL/TNFSF13 were associated with improved event-free survival after adjusting for age and stage (HR = 0.64, 95% CI 0.43-0.95; p = 0.03). High expression of APRIL/TNFSF13 tumor transcripts was significantly associated with improved OS in TCGA-SKCM (HR = 0.69, 95% CI 0.52-0.93; p = 0.01) and in Moffitt Melanoma patients (HR = 0.51, 95% CI: 0.32-0.82; p = 0.006). Further incorporation of CXCL13 and CXCL10 tumor transcript levels in a 3-gene index revealed that high APRIL/CXCL10/CXCL13 expression was associated with improved OS in the TCGA SKCM cohort (HR = 0.42, 95% CI 0.19-0.94; p = 0.035). Melanoma differentially expressed genes positively associated with high APRIL/CXCL10/CXCL13 tumor expression were linked to tumor infiltration by a diverse array of proinflammatory immune cell types.ConclusionSerum protein and tumor transcript levels of APRIL/TNFSF13 are associated with improved survival outcomes. Patients exhibiting high coordinate expression of APRIL/CXCL10/CXCL13 transcripts in their tumors displayed superior OS. Further investigation of TLS-kine expression profiles related to clinical outcomes in larger cohort studies is warranted

RESEARCH PROGRESS ON CUTTING TECHNOLOGY OF SIC MONO-CRYSTAL WAFER WITH WIRE SAW

Having a unique physical characteristics and stable semiconductor properties,silicon carbide（ Si C） monocrystal wafer has been widely used in integrated circuits,space optics and other fields.In manufacturing process of Si C monocrystal wafer,cutting is primary key process,which the cutting costs accounts for more than 50% of the whole wafer processing costs.In this paper,the datum and relevant literature of domestic and foreign were reviewed to,the current research status of Si C cutting technology,especially cutting with wire saw,and cutting equipment were studied.Moreover,the existing problems in Si C cut by wire saw and in cutting equipment was analyzed.It is proposed that the future researching direction of Si C wafer cutting technology by wire saw

Wire Vibration Modeling and Experimental Analysis for Wire Saw Machining

Surface roughness is the key index point of wire saw processing silicon carbide (SiC). Many factors influence wafer surface quality, which is determined by the motion of the wire relative to the part. The vibration characteristic of wire saw and the process parameters are concerned factors in this paper, which presents a wire vibration model to study the wire saw vibration law. Experimental studies of a stationary wire are conducted to calibrate the damping coefficient and experimental studies of a moving wire are used to validate the developed model. Simulation, theoretical, and experimental data for wire vibrations during a variety of machining processes are found to compare very well, and the effects of various wire saw process parameters are investigated to analyze the influences of process parameters on wire vibration. It was shown that increasing the wire tension and feed rate, or decreeing the wire length, decreases the wire\u27s first dominant frequency, and that changes in the wire velocity had a negligible effect. Finally, the measurement of the surface morphology and wire saw vibrations for different processing parameters was conducted, and it was seen that increases in the wire velocity and wire tension increases part surface quality and decreases processing time, while an increase in the feed rate decreases both part surface quality and processing time. The results show a clear correlation between the amplitude of the wire vibration outside of the processing zone and the part surface quality

Co-simulation of Six DOF Wire Driven Parallel Mechanism Based on ADAMS and Matlab

The dynamic model of the 6 DOF Wire Driven Parallel Mechanism (WDPM) system is introduced. Based on MATLAB system, the simulation of the inverse dynamic model is achieved. According to the simulation result, the mechanical model for the WDPM system is reasonable. Using ADAMS system, the dynamic model of the virtual prototype is verified by the simulation analysis. The combined control model based on ADAMS/Simulink is derived. The WDPM control system is designed with MATLAB/Simulink. The torque control method is selected for the outer ring and the PD control method for the inner ring. Combined with the ADAMS control model and control law design, the interactive simulation analysis of the WDPM system is completed. According to the simulation results of the spatial circle tracking and line tracking at the end of the moving platform, the tracking error can be reduced by the designed control algorithm. The minimum tracking error is 0.2 mm to 0.3 mm. Therefore, the theoretical foundation for designing hardware systems of the WDPM control system is established

Co-simulation of Six DOF Wire Driven Parallel Mechanism Based on ADAMS and Matlab

The dynamic model of the 6 DOF Wire Driven Parallel Mechanism (WDPM) system is introduced. Based on MATLAB system, the simulation of the inverse dynamic model is achieved. According to the simulation result, the mechanical model for the WDPM system is reasonable. Using ADAMS system, the dynamic model of the virtual prototype is verified by the simulation analysis. The combined control model based on ADAMS/Simulink is derived. The WDPM control system is designed with MATLAB/Simulink. The torque control method is selected for the outer ring and the PD control method for the inner ring. Combined with the ADAMS control model and control law design, the interactive simulation analysis of the WDPM system is completed. According to the simulation results of the spatial circle tracking and line tracking at the end of the moving platform, the tracking error can be reduced by the designed control algorithm. The minimum tracking error is 0.2 mm to 0.3 mm. Therefore, the theoretical foundation for designing hardware systems of the WDPM control system is established

Force Modeling of Silicon Monocrystal Wire Saw Machining

Wire saw machining is often used to cut hard and brittle materials, especially wafers in the semiconductor and optoelectronics industries. The cutting forces strongly effect part quality. Based on analyzing the forces generated from the chip deformation and friction of a single abrasive, an analytical force model is developed. The model is extended to a wire saw cutting force model and is used to explain the relationship between the cutting force and the part feed rate, wire velocity, and contact length between the wire and part. Silicon (Si) monocrystal machining is used to experimentally validate the proposed model. The results show that when machining Si monocrystal the average errors between the experimental and predicted normal and tangential cutting forces are 10.9% and 18.6%, respectively

SIMULATION AND EXPERIMENTAL STUDY ON THE STATIC STIFFNESS OF HIGH SPEED MOTORIZED SPINDLE

The static stiffness of the spindle is an important index to evaluate the static characteristics of the motorized spindle,which is essential to ensure the machining accuracy of precision CNC machine tools.Based on the calculation formulas of cutting force under typical conditions and those of radial stiffness of angular contact ball bearing,the axial deformation in front of the spindle,as well as the static stiffness in the specified condition,were obtained through the 3D finite element model of rotor-bearing system.The static stiffness test was performed on the experimental platform.By comparing the simulation results and the experimental results,the validity of the finite element model was indirectly verified.Based on the reliable finite element model,the variations of the static stiffness of the spindle with the preloads of the front and rear bearing groups were gained

Mechanisms of Zuogui Pill in Treating Osteoporosis: Perspective from Bone Marrow Mesenchymal Stem Cells

The current treatment strategies for osteoporosis (OP) involve promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). According to a theory of traditional Chinese medicine (TCM), the kidneys contain an “essence” that regulate bone metabolism and generate marrow. Kidney disorders are therefore considered to be a major cause of OP as per the principles of TCM, which recommends kidney-tonifying treatments for OP. The Zuogui pill (ZGP) is a classic kidney-tonifying medication that effectively improves OP symptoms. Studies have shown that ZGP can promote the osteogenic differentiation of BMSCs, providing scientific evidence for the TCM theory linking kidneys with bone metabolism. In this review, we have provided an overview of recent studies that examined the underlying mechanisms of ZGP mediated regulation of BMSC osteogenic and adipogenic differentiation

Experimental and Numerical Studies of Wire Vibrations in Bonded Abrasive Wire Saw Processing

Bonded Abrasive Wire (BAW) saw slicing is a popular method for silicon carbide wafer production; however, the wires are highly susceptible to vibrations. In this paper, a vibration model of the wire saw is presented, and a numerical analysis of this model, which is confirmed by experiments, is developed. The experiments show that the model can predict vibration characteristics of wire saw with no processing or processing and the biggest error of model in frequency domain is 10.6%. Moreover, the wire tension is an important factor for wire saw vibration. The experiments show that a 50% increase in tension may make a 43.2% increase in vibration frequency, and the relationship is not linear depended on tension control device