Reduced Claudin-12 Expression Predicts Poor Prognosis in Cervical Cancer

Background: Within the claudin (CLDN) family, CLDN12 mRNA expression is altered in various types of cancer, but its clinicopathological relevance has yet to be established due to the absence of specific antibodies (Abs) with broad applications. Methods: We generated a monoclonal Ab (mAb) against human/mouse CLDN12 and verified its specificity. By performing immunohistochemical staining and semiquantification, we evaluated the relationship between CLDN12 expression and clinicopathological parameters in tissues from 138 cases of cervical cancer. Results: Western blot and immunohistochemical analyses revealed that the established mAb selectively recognized the CLDN12 protein. Twenty six of the 138 cases (18.8%) showed low CLDN12 expression, and the disease-specific survival (DSS) and recurrence-free survival rates were significantly decreased compared with those in the high CLDN12 expression group. We also demonstrated, via univariable and multivariable analyses, that the low CLDN12 expression represents a significant prognostic factor for the DSS of cervical cancer patients (HR 3.412, p = 0.002 and HR 2.615, p = 0.029, respectively). Conclusions: It can be concluded that a reduced CLDN12 expression predicts a poor outcome for cervical cancer. The novel anti-CLDN12 mAb could be a valuable tool to evaluate the biological relevance of the CLDN12 expression in diverse cancer types and other diseases.     

Progress in pressureless sintering of boron carbide ceramics – a review

ABSTRACT

Boron carbide (B₄C) ceramics has many outstanding performance, such as extremely high hardness, low density, high melting point, high elastic modulus, high thermoelectromotive force, high chemical resistance, high neutron absorption cross section, high impact and excellent wear resistance. Therefore, B₄C ceramics can be used in various industrial applications, such as lightweight ceramic armour, high temperature thermocouples, neutron absorber, reactor control rods in nuclear power engineering, polishing media for hard materials, abrasive media for lapping and grinding, and wear resistant components (blasting nozzles, die tips and grinding wheels). Pressureless sintering is the method with industrialised application value for B₄C ceramics, however, it is impossible to sinter pure B₄C ceramics to high densities without additives by pressureless sintering. So sintering additives must be used to promote the densification of B₄C ceramics. The different sintering additives used to promote the densification of boron carbide will be described in this review, including carbon additives, metallic additives, oxide additives, non-oxide additives, combined additives and rare earth oxide additives. Finally, the recent research trends for sintering methods and sintering additives of B₄C ceramics will also be proposed.     

Dimeric C34 Derivatives Linked through Disulfide Bridges as New HIV-1 Fusion Inhibitors

C34, a 34-mer fragment peptide, is contained in the HIV-1 envelope protein gp41. A dimeric derivative of C34 linked through a disulfide bridge at its C terminus was synthesized and found to display potent anti-HIV activity, comparable with that of a previously reported PEGylated dimer of C34REG. The reduction in the size of the linker moiety for dimerization was thus successful, and this result might shed some light on the mechanism of the suppression of six-helix bundle formation by these C34 dimeric derivatives. Addition of a Gly-Cys(CH₂CONH₂)-Gly-Gly motif at the N-terminal position of a C34 monomeric derivative significantly increased the anti-HIV-1 activity. This moiety functions as a new pharmacophore, and this might provide a useful insight into the design of potent HIV-1 fusion inhibitors.     

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds

Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell–deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.     

Polarity Effect and Electromagnetic Radiation of Partial Discharge Accompanying Growth of Electrical Tree

We have investigated the characteristics of radiated electromagnetic (EM) waves from positive and negative partial discharges (PD) in epoxy resin and cross‐linked polyethylene. We found that there is a correlation among the EM level from PD, the positive PD current, and electrical trees. Therefore, the growth of an electrical tree produces a lot of positive PD. We have also investigated the characteristics of the frequency region of EM waves from PD in air, insulating oil, and liquid epoxy in addition to the above insulators. EM waves were detected in the frequency region of 40 MHz to 300 MHz from positive and negative PD in epoxy resin and cross‐linked polyethylene. EM waves were also detected in the frequency region of 40 MHz to 150 MHz from positive and negative PD in air. In the case of insulating oil and liquid epoxy, EM waves were detected in the frequency regions of 40 MHz to 150 MHz from positive PD, and 40 MHz to 250 MHz from negative PD. The frequency region differed depending on the material and the discharge polarity. Our investigation indicates that the cause is differences in electric field strength at the time of PD occurrence.     

A method for testing the interface toughness of ceramic environmental barrier coatings (EBCs) on ceramic matrix composites (CMCs)

A simple interface fracture test for ceramic environmental barrier coatings (EBCs) on ceramic matrix composites (CMCs) was developed. A variation on the asymmetric double cantilever beam (ADCB) test was proposed so that the interface toughness could be measured in a small specimen of simple shape without applying interlaminar loading to the CMC substrate. The proposed test was applied to an EBC consisting of a mullite layer and Si bond coat on a monolithic SiC substrate. A pre-crack was introduced by pop-in cracking, and then a notch overlapping the pre-crack was machined. The pre-crack was opened by inserting a wedge into the notch. From the critical notch opening displacement the crack starts to propagate, interface toughness is calculated. The measured interface toughness was 4.1?J/m2. Finally, the application range of the test was discussed and suggestions were made for introduction of the notch and pre-crack.     

Geosynthetic-sheet pile reinforced foundation for mitigation of earthquake and tsunami induced damage of breakwater

Earthquake and tsunami impose great threats on the stability of a breakwater. Foundation of the breakwater is weakened by these forces, and it may result in collapse of the breakwater. Lateral flow of seabed soils take place beneath the breakwater, and excess pore water pressure is generated in the foundation by an earthquake that precedes tsunami. These factors may lead to excessive settlement and horizontal displacement of the breakwater. Tsunami introduces additional instability to the deformed breakwater. Due to water level difference between seaside and harborside of the breakwater during a tsunami, seepage occurs through its foundation, and it may cause pipping of seabed soils. Tsunami induced scouring of mound is also a big problem for the stability of the breakwater foundation. Finally, these result in failure of the breakwater foundation. Due to failure of its foundation, the breakwater may collapse and cannot block the tsunami. It results in entering of the tsunami in coastal areas. In order to make a breakwater resilient against earthquake and tsunami induced damage, reinforcing countermeasures were developed for foundation of a breakwater. Geogrid, gabions and sheet piles were used for reinforcing a foundation model. The effectiveness of the model is evaluated through physical modeling for mitigating the earthquake and tsunami induced damage. Shaking table tests were performed to determine the effectiveness of the reinforced model under different earthquake loadings. Tsunami overflow test was conducted on the same deformed model in order to see the effects of tsunami on the model. Comparisons were made between the unreinforced and reinforced foundations, and it was observed during the tests that the reinforced foundation performed well in reducing the damage of the breakwater brought by the earthquake and tsunami. Overall, this study is useful for practice engineering, and the reinforced foundation model can be adopted for designing a breakwater foundation to reduce damage triggered by an earthquake and tsunami in the future.