In Situ PD-L1 Expression in Oral Squamous Cell Carcinoma Is Induced by Heterogeneous Mechanisms among Patients

The expression of programmed death ligand-1 (PD-L1) is controlled by complex mechanisms. The elucidation of the molecular mechanisms of PD-L1 expression is important for the exploration of new insights into PD-1 blockade therapy. Detailed mechanisms of the in situ expression of PD-L1 in tissues of oral squamous cell carcinomas (OSCCs) have not yet been clarified. We examined the mechanisms of PD-L1 expression focusing on the phosphorylation of downstream molecules of epidermal growth factor (EGF) and interferon gamma (IFN-γ) signaling in vitro and in vivo by immunoblotting and multi-fluorescence immunohistochemistry (MF-IHC), respectively. The in vitro experiments demonstrated that PD-L1 expression in OSCC cell lines is upregulated by EGF via the EGF receptor (EGFR)/PI3K/AKT pathway, the EGFR/STAT1 pathway, and the EGFR/MEK/ERK pathway, and by IFN-γ via the JAK2/STAT1 pathway. MF-IHC demonstrated that STAT1 and EGFR phosphorylation was frequently shown in PD-L1-positive cases and STAT1 phosphorylation was correlated with lymphocyte infiltration and EGFR phosphorylation. Moreover, the phosphorylation pattern of the related molecules in PD-L1-positive cells differed among the cases investigated. These findings indicate that PD-L1 expression mechanisms differ depending on the tissue environment and suggest that the examination of the tissue environment and molecular alterations of cancer cells affecting PD-L1 expression make it necessary for each patient to choose the appropriate combination drugs for PD-1 blockade cancer treatment.     

Myo5b Transports Fibronectin-Containing Vesicles and Facilitates FN1 Secretion from Human Pleural Mesothelial Cells

Pleural mesothelial cells (PMCs) play a central role in the progression of pleural fibrosis. As pleural injury progresses to fibrosis, PMCs transition to mesenchymal myofibroblast via mesothelial mesenchymal transition (MesoMT), and produce extracellular matrix (ECM) proteins including collagen and fibronectin (FN1). FN1 plays an important role in ECM maturation and facilitates ECM-myofibroblast interaction, thus facilitating fibrosis. However, the mechanism of FN1 secretion is poorly understood. We report here that myosin 5b (Myo5b) plays a critical role in the transportation and secretion of FN1 from human pleural mesothelial cells (HPMCs). TGF-β significantly increased the expression and secretion of FN1 from HPMCs and facilitates the close association of Myo5B with FN1 and Rab11b. Moreover, Myo5b directly binds to GTP bound Rab11b (Rab11b-GTP) but not GDP bound Rab11b. Myo5b or Rab11b knockdown via siRNA significantly attenuated the secretion of FN1 without changing FN1 expression. TGF-β also induced Rab11b-GTP formation, and Rab11b-GTP but not Rab11b-GDP significantly activated the actin-activated ATPase activity of Myo5B. Live cell imaging revealed that Myo5b- and FN1-containing vesicles continuously moved together in a single direction. These results support that Myo5b and Rab11b play an important role in FN1 transportation and secretion from HPMCs, and consequently may contribute to the development of pleural fibrosis.     

In-service inspections and R&D of PCCVs in Japan

In Japan, the following five plants in operation use prestressed concrete containment vessels (PCCVs): Tsuruga #2 (in operation in 1987), Ohi #3 and #4 (in operation in 1991 and 1993, respectively), and Genkai #3 and #4 (in operation in 1994 and 1997, respectively). These plants have adopted the hemispherical dome type PCCV with two or three buttresses and unbonded prestressing system. For the above five PCCVs, lift-off tests in the in-service inspection have been carried out 1, 3 and 5 years after the beginning of operation. In addition, concrete strain and temperature have been measured periodically. This paper presents the in-service inspection methods and results of the lift-off tests and the measurement of concrete strain. The given results are as follows. Measured strain shows good agreement with calculated creep and shrinkage strain, so tendon tensile force can be predicted by the design method using calculated strain, and it also matches well the results of the lift-off tests.     

Molding of PBO fabric reinforced thermoplastic composite to achieve high fiber volume fraction

In fiber‐reinforced plastic materials, the fiber volume fraction is one of the most important parameters, and it strongly influences the composite properties. However, it is hard to improve impregnation and the fiber volume fraction in fiber‐reinforced thermoplastics because thermoplastic resins have high melt viscosities. This study explored a reformative solution impregnation method for molding fabric‐reinforced thermoplastic composites with a high fiber volume fraction. The fiber volume fraction was significantly increased, to 60%, which is equal to that of fiber‐reinforced thermosetting plastic materials. A comparison indicated that a fiber‐reinforced thermoplastic and a fiber‐reinforced thermosetting plastic with the same reinforcing fiber had similar tensile properties and that the proposed molding method is effective in thermoplastic composite manufacture. POLYM. COMPOS., 34:953–958, 2013. © 2013 Society of Plastics Engineers     

Simultaneous brightness contrast with three different stimuli: 2D, 3D,and D-up

In this study, simultaneous brightness contrast was investigated using three different devices: 2D (paper), 3D (space), and D-up. The paper stimuli were made by printing papers, the space stimuli were produced by illumination in a two-rooms experimental booth, and the D-up stimuli were shown to subjects using a D-up viewer. The brightness of test patches was judged by the amounts of whiteness and blackness. The results were different among the devices; however, if the whiteness of the test patches was plotted for the luminance contrast of the test patch versus the surround, all the data points were expressed by nonlinear equations. Data from the space stimuli were expressed by only one equation; those from the paper stimuli were also expressed by the nonlinear equation but with different coefficients for each test patch. The results from D-up were between those of the space and paper experiments. All the results were explained in relation to the hypothesized illuminated space over the surrounds. The difference among devices was explained by the whiteness of the surround being transferred to the illumination.