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.     

Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice

Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4⁺ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis.     

Neural mechanism of pupillary dilation elicited by electro-acupuncture stimulation in anesthetized rats

The neural mechanisms to reflex dilation elicited by electro-acupuncture stimulation were investigated in anesthetized rats. Two needles, with 160 microns diameter and about 5 mm apart, were inserted into the skin and underlying muscle of a hindpaw. Repetitive 20 Hz, 0.5 ms electrical pulses at various intensities were used for stimulation for 30s. The pupil size was magnified about 44 times via a microscope and was continuously recorded on a videotape. Electro-acupuncture stimulation at more than 0.5 up to 6 mA induced stimulus intensity-dependent pupil dilation. These responses were abolished by the severance of the sciatic and saphenous nerve of the stimulated hindlimb. Compound action potentials were recorded from the distal cut end of the tibial of a saphenous nerve following electro-acupuncture stimulation of the hindpaw. The mean threshold of the compound action potentials of the myelinated fibers in saphenous nerves was 0.18 mA, while that of unmyelinated fibers was 3.0 mA. The mean threshold of the compound action potentials of the myelinated fibers in the tibial nerve was 0.20 mA of unmyelinated fibers was 3.3 mA. Severance of bilateral trunks did not affect the response, while severance of the third cranial nerves abolished the responses. In conclusion, electro-acupuncture stimulation applied to the hindpaws of the anesthetized rats induced excitation of myelinated or of both myelinated and unmyelinated afferent fibers of the tibial and saphenous nerve, and involved a reflex response of pupil dilation through the third cranial parasympathetic efferent nerve.     

Angular memory and frequency interferometry for mean heightprofiling of a rough surface

The polarimetric angular memory effect is applied to obtain the average topographic height of a rough surface. This novel effect improves the height sensitivity while maintaining a good degree of correlation between the sensors. By using a reference flat surface, the interferometric phase is linearly related to the mean topographic height. The combination of angular memory and wideband frequency interferometry (AMFI) is realized and offers a means to design a robust interferometric system. Extension of the technique to the pulse scattering problem is studied through the two-frequency mutual coherence function, and its time-domain transform provides an equivalent way to obtain the mean topographic height by combining both spatial and temporal diversity. Millimeter-wave (MMW) experiments are conducted with rough surfaces of different statistics and scattering media of different types (gravel, sand, and rough surfaces) to prove the effectiveness of the technique     

Establishment time of liquid flow in a bath agitated by bottom gas injection

The establishment time of gas-liquid two-phase flows in a cylindrical bath agitated by bottom gas injection through a central single-hole bottom nozzle was investigated. Because the turbulence intensity in the bath was comparable to or larger than the unity, the conventional definition of the flow establishment time based on the history of mean velocity was not suitable for the present case. In fact, it was difficult to determine the flow establishment time based on the well-known 90 or 99 pct criterion for the mean velocity. Accordingly, two methods of determining the flow establishment time by focusing on the turbulence components instead of the mean velocity components were proposed. Velocity measurements were made with a two-channel laser Doppler velocimeter. The flow establishment time was correlated as a function of gas flow rate. Close agreement was obtained by the two methods.     

Body effects on SAR distributions for microwave exposures in a realistic model of the human head.

The finite-difference time-domain (FDTD) simulations of specific absorption rate (SAR) in a human head exposed to microwaves have, to date, been carried out on models of the head only. This was because it was believed that the body effects on the average SAR of the head could be ignored at high frequencies of around 1 GHz. That opinion, however, was based on inappropriate calculation conditions and is therefore unreliable. In this paper, we have re-examined the body effects on the SAR distributions in a realistic homogeneous model of the adult head exposed to microwaves. We found that the SAR on the eye surface of the head-only model exposed to E-polarized waves was 31% smaller than that of the whole-body model at 900 MHz, and 43% larger at 1.5 GHz. For a size that can practically be considered whole-body, it is necessary to have the top of the head to the belly for 900 MHz and to the chest area for 1.5 GHz. The previously unclear body effects of H-polarized waves were assumed to be less than those of E-polarized waves, suggesting that the chest area would be sufficient for both frequencies.     

Operation of HTS Toggle-Flip-Flop Circuit With Improved Layout Design

Toggle-flip-flop (T-FF) is one of the most important high-T_c superconducting single-flux quantum (HTS SFQ) circuit components and has been designed and fabricated by using YBa₂Cu₃ O_7-delta ramp-edge junction technology. The circuit layout of the T-FF was improved to suppress the junction critical current (I_c) spread in the circuit. Test circuits, which include a T-FF with a single output for evaluating the logic operation and measuring the operating frequency, were fabricated and their operation characteristics were investigated. The T-FF circuit with a single output was successfully operated and finite direct current (dc) supply current margins were obtained at temperatures from 27 to 34 K. Moreover, the maximum operating frequency of the T-FF was estimated to be 360 GHz at 4.2 K and 114 GHz at 41 K. In addition, reduction of dc supply current margins due to thermal noise was also investigated. According to the numerical simulation in which parasitic inductances were taken into account, the narrowest margin in the T-FF circuit wider than plusmn10% was maintained with a bit-error rate (BER) of 10^-6 up to 40 K     

Series resonant ZCS‐PFM DC‐DC power converter with high‐frequency high‐voltage transformer link for high‐power magnetron drive

This paper presents a single lossless inductive snubber‐assisted ZCS‐PFM series resonant DC‐DC power converter with a high‐frequency high‐voltage transformer link for industrial‐use high‐power magnetron drive. The current flowing through the active power switches rises gradually at a turned‐on transient state with the aid of a single lossless snubber inductor, and ZCS turn‐on commutation based on overlapping current can be achieved via the wide range pulse frequency modulation control scheme. The high‐frequency high‐voltage transformer primary side resonant current always becomes continuous operation mode, by electromagnetic loose coupling design of the high‐frequency high‐voltage transformer and the magnetizing inductance of the high‐frequency high‐voltage transformer. As a result, this high‐voltage power converter circuit for the magnetron can achieve a complete zero current soft switching under the condition of broad width gate voltage signals. Furthermore, this high‐voltage DC‐DC power converter circuit can regulate the output power from zero to full over audible frequency range via the two resonant frequency circuit design. Its operating performances are evaluated and discussed on the basis of the power loss analysis simulation and the experimental results from a practical point of view. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 153(3): 79–87, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20126     

Fractal dimension of the grain boundary fracture in creep-fracture of cobalt-based heat resistant alloys

The effects of grain boundary configuration and creep conditions on the fractal dimension of the grain boundary fracture (D _f) were investigated using commercial cobalt-based heat resistant alloys, namely, HS-21 and L-605 alloys. Creep-rupture experiments were carried out under the initial creep stresses of 19.6–176 MPa in the temperature range from 1089–1422 K in air. The value of D _f was larger in specimens with serrated grain boundaries than in those with straight grain boundaries in the HS-21 alloy under the same creep condition, and the difference in the value of D _f between these specimens was large in the scale range of the analysis which was less than about one grain boundary length. However, there was almost no difference in the value of D _f between the specimens with serrated grain boundaries and those with straight grain boundaries in the L-605 alloy, because there was no obvious difference in the microstructure between these specimens. The value of D _f increased with decreasing creep stress in the scale range of the fractal analysis larger than about one grain boundary length in both HS-21 and L-605 alloys, while the stress dependence of D _f was larger in the HS-21 alloy. The stress dependence of D _f was explained by the stress dependence on the number of grain boundary microcracks linked to the fracture surface. The value of D _f estimated in the scale range smaller than about one grain boundary length showed essentially no stress dependence in both L-605 and HS-21 alloys.