Observation of Al-lines in LSI devices by ultra-high voltage electron microscope

To clarify the mechanism caused by multi-layer effect, the ultra-HVEM at 2MeV is powerful because it has an excellent penetration power for specimens. By thinning the Si-substrate of LSI devices, we can carry out in-situ observations of phenomena arising in the process layers; in particular, we can observe the specimens without removing the passivation layers that strongly affect the generation of these phenomena. We show how the orientation of Al-lines depends on the step of process and how it relates to the incidence of stressmigration voids. From in-situ observation of electromigration in Al-lines with bamboo structure, it is seen that the main route of electromigration is the interface between the line and the passivation layer, and the migration is enhanced when a small gap exits in the interface

Three-dimensional, Computer-tomographic Analysis of Membrane Proteins (TrkA, caveolin, clathrin) in PC12 Cells

Signaling of nerve growth factor (NGF) and its receptor (TrkA) promotes neuronal differentiation, synapse formation and survival. It has been known that the complex of NGF and TrkA is internalized into the cytoplasm and transported for further signal transduction, but the ultrastructural information of this process is virtually unknown. In order to clarify the relationship between the internalization of TrkA and the membrane-associated proteins (caveolin and clathrin), the localization and three-dimensional structures of those proteins were examined with computer tomography of high voltage electron microscopy in PC12 cells. TrkA immunoreactivity was found only at definite areas in the plasma membrane, as ring and cluster structures. Its 3D image indicated that those cluster structures contained small pits, which did not appear to be typical caveolae in size and shape. 3D images of clathrin and caveolin-1 immunoreactivities indicated that the formation of those small pits was associated with clathrin, but not with caveolin-1. Caveolin-1 immunoreactivity was found as a mesh-like structure just beneath the plasma membrane. These results suggest that clathrin rather than caveolin is mainly involved in the process of TrkA internalization, at least in differentiated PC12 cells

Clinical and dosimetric factors for symptomatic radiation pneumonitis after stereotactic body radiotherapy for early-stage non-small cell lung cancer

Background and purpose: The present study attempted to identify risk factors for symptomatic radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) in patients with early-stage non-small cell lung cancer (NSCLC). Materials and methods: We reviewed 244 patients with early-stage NSCLC treated with SBRT. The primary endpoint was the incidence of grade ≥2 RP. Gray’s test was performed to examine the relationship between clinical risk factors and grade ≥2 RP, and the Fine-Gray model was used for a multivariate analysis. The effects of each dose parameter on grade ≥2 RP were evaluated with the Fine-Gray model and optimal thresholds were tested using receiver operating characteristic (ROC) curves. Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥2 RP was 15.3%. Gray’s test revealed that tumor size, a central tumor, interstitial pneumonia, and the biologically effective dose correlated with RP. In the multivariate analysis, a central tumor and interstitial pneumonia remained significant factors (p 16.7% was the best indicator of symptomatic RP among dose parameters. Conclusion: The present results suggest that a central tumor and interstitial pneumonia are independent risk factors for symptomatic RP and lung V10 ≤16.7% is recommended as the threshold in SBRT

Symptomatic radiation-induced rib fractures after stereotactic body radiotherapy for early-stage non-small cell lung cancer

Background and purpose: The present study investigated the relationships between the risk of radiation-induced rib fractures (RIRF) and clinical and dosimetric factors in stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). We also examined dosimetric parameters associated with symptomatic or asymptomatic RIRF and the dosimetric threshold for symptomatic RIRF. Materials and methods: We reviewed 244 cases of early-stage NSCLC treated with SBRT. Gray’s test and the Fine-Gray model were performed to examine the relationships between clinical and dosimetric factors and grade ≥ 2 (i.e., symptomatic) RIRF. The effects of each dose parameter on grade ≥ 1 and ≥ 2 RIRF were assessed with the Fine-Gray model. The t-test was used to compare each dose parameter between the grade 1 and grade ≥ 2 groups. Optimal thresholds were tested using receiver operating characteristic (ROC) curves. Results: With a median follow-up period of 48 months, the 4-year cumulative incidence of grade ≥ 1 and grade ≥ 2 RIRF were 26.4 % and 8.0 %, respectively. Regarding clinical factors, only age was associated with the development of grade ≥ 2 RIRF (p = 0.024). Among dosimetric parameters, only V40Gy significantly differed between the grade 1 and grade ≥ 2 groups (p = 0.015). The ROC curve analysis of grade ≥ 2 RIRF showed that the optimal diagnostic thresholds for D3cc, D4cc, D5cc, and V40Gy were 45.86 Gy (area under the curve [AUC], 0.706), 39.02 Gy (AUC, 0.705), 41.62 Gy (AUC, 0.702), and 3.83 cc (AUC, 0.730), respectively. These results showed that V40Gy ≤ 3.83 cc was the best indicator of grade ≥ 2 RIRF. The 4-year incidence of grade ≥ 2 RIRF in the V40Gy ≤ 3.83 cc vs. > 3.83 cc groups was 1.8 % vs. 14.2 % (p = 0.001). Conclusion: The present results recommend V40Gy ≤ 3.83 cc as the threshold for grade ≥ 2 RIRF in SBRT

Comparison of Recurrence Patterns between Adenocarcinoma and Squamous Cell Carcinoma after Stereotactic Body Radiotherapy for Early-Stage Lung Cancer

We compared recurrence patterns between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) after stereotactic body radiotherapy (SBRT) for early-stage lung cancer. Patients with ADC and SCC histology, who were treated with SBRT for clinical stage IA1-IIA lung cancer at our institution, were included in the analysis. The rates of disease-free survival (DFS), overall survival (OS), local recurrence (LR), lymph node metastasis (LNM), and distant metastasis (DM) were calculated using the Kaplan–Meier method or the cumulative incidence function. Among the 204 patients analyzed, 138 and 66 were in the ADC and SCC groups, respectively. The median follow-up period was 60 months. The five-year DFS and OS rates were 57% vs. 41% and 69% vs. 48% in the ADC and SCC groups, respectively (p = 0.015 and 0.019, respectively). In the multivariate analysis, the histological type was not associated with DFS or OS. Five-year LR, LNM, and DM rates were 10% vs. 24%, 12% vs. 20%, and 25% vs. 27% in the ADC and SCC groups, respectively (p = 0.0067, 0.074, and 0.67, respectively). The multivariate analysis identified the histological type of SCC as an independent factor for LR (hazard ratio, 2.41; 95% confidence interval, 1.21–4.77; p = 0.012). The present results suggest that the risk of LR after SBRT is higher for SCC than for ADC