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.     

Characterization of anisotropic gas permeability and thermomechanical properties of highly textured porous alumina

Porous alumina with a highly textured microstructure was fabricated by pulse electric current sintering (PECS) using alumina platelets. Highly oriented porous alumina with a porosity of 3%–50% was obtained by a pressure-controlled method of PECS. The properties of the highly textured porous alumina were measured in two directions. The nitrogen gas permeance and thermal conductivity at room temperature were higher in the direction along the platelet length due to the higher continuity of pores and the connectivity of alumina platelets, respectively. The anisotropy of the thermal conductivity at room temperature was investigated and explained by the effect of grain size of platelets as well as morphology and orientation of pores. The bending strength was higher with the loading direction along the platelet thickness. The thermal shock strength was clearly different in the two directions. The difference in the thermal shock strength was investigated by the measurement of properties and thermal stress analysis.     

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.     

Supramolecular Zn(II)-Dipicolylamine-Azobenzene-Aminocyclodextrin-ATP Complex: Design and ATP Recognition in Water

Cyclodextrins (CyDs) are water-soluble host molecules possessing a nanosized hydrophobic cavity. In the realm of molecular recognition, this cavity is used not only as a recognition site but also as a reaction medium, where a hydrophobic sensor recognizes a guest molecule. Based on the latter concept, we have designed a novel supramolecular sensing system composed of Zn(II)-dipicolylamine metal complex-based azobenzene (1-Zn) and 3A-amino-3A-deoxy-(2AS,3AS)-γ-cyclodextrin (3-NH₂-γ-CyD) for sensing adenosine-5′-triphosphate (ATP). 1-Zn showed redshifts in the UV-Vis spectra and induced circular dichroism (ICD) only when both ATP and 3-NH₂-γ-CyD were present. Calculations of equilibrium constants indicated that the amino group of 3-NH₂-γ-CyD was involved in the formation of supramolecular 1-Zn/3-NH₂-γ-CyD/ATP. The Job plot of the ICD spectral response revealed that the stoichiometry of 1-Zn/3-NH₂-γ-CyD/ATP was 2:1:1. The pH effect was examined and 1-Zn/3-NH₂-γ-CyD/ATP was most stable in the neutral condition. The NOESY spectrum suggested the localization of 1-Zn in the 3-NH₂-γ-CyD cavity. Based on the obtained results, the metal coordination interaction of 1-Zn and the electrostatic interaction of 3-NH₂-γ-CyD were found to take place for ATP recognition. The “reaction medium approach” enabled us to develop a supramolecular sensing system that undergoes multi-point interactions in water. This study is the first step in the design of a selective sensing system based on a good understanding of supramolecular structures.     

Effect of Electron Correlation on Phonon Spectra in Cuprates

We examine theoretically the phonon dynamics in the electron-phonon-coupled systems. The model Hamiltonian is a one-dimensional Hubbard model where the hopping of electrons induces the electron-phonon coupling. The numerically exact diagonalization of the Hamiltonian with truncation of the total number of phonons is performed. We calculate the phonon excitation spectra and find that the softening of phonons occurs in insulating case, and a diffusive character appears in the metallic case. We also calculate the charge and spin excitation spectra and find that the dynamics of the phonon coupled with the hopping of electrons is affected by the low energy charge and spin excitations.     

Characterization of localized states in thin PrBa2Cu3O7−x tunnel barriers

Characteristic power-law dependence of junction conductance on temperature was confirmed at low temperatures fora,b-axis oriented Au/PrBa₂Cu₃O_7−x /YBa₂Cu₃O_7−y junctions with a PrBa₂Cu₃O_7−x layer thinner than 30 nm, indicating that current transport via a small number of localized states was predominant. The radius and the density of the localized states were estimated to be 1.1 nm and 5.0x10¹⁹ eV⁻¹ cm⁻³, respectively. Transport measurement at 1.7 K in a magnetic field of up to 6 T revealed no indication of on-site Coulomb repulsion of electrons in the localized states. These results support the possibility of resonant tunneling of Cooper pairs in superconductor-insulator-superconductor junctions with a thin PrBa₂Cu₃O_7−x tunnel barrier.     

Alteration of GABAA receptor alpha 1-subunit mRNA in mouse brain following continuous ethanol inhalation

OBJECTIVE: To evaluate what nursing home medical directors actually do, what they and other nursing home personnel believe would be desirable to do, and what problems and deficiencies are perceived. DESIGN: Mail survey with follow-up telephone interview when necessary. SETTING: Forty-five nursing facilities in upstate New York. PARTICIPANTS: The medical directors, administrators, and directors of nursing of the 45 facilities. MEASUREMENTS: Inventory of what medical directors reported as to their actual activities and time spent, and of what they, the administrators, and the directors of nursing felt should be their responsibilities and activities under ideal circumstances. RESULTS: For part-time medical directors, self-reported time spent on medical directorship activities averaged 12 hours per month; of all directors, 45% spent 8 hours or less per month. Proportion of time spent on various specific activities varied widely. There was general agreement that substantially more time should be spent, in particular, on evaluating and addressing problems of adequacy and quality of care, communicating with attending physicians about problems, and assisting with inservice training programs. CONCLUSIONS: To fill the role adequately, more time should be spent by many part-time medical directors, which will require greater financial commitment by facilities and reimbursement systems. Efforts need to made to better coordinate the expectations of medical directors and facility staff.     

An on-chip active decoupling circuit to suppress crosstalk in deep-submicron CMOS mixed-signal SoCs

A decoupling circuit using an operational amplifier is proposed to suppress substrate crosstalk in mixed-signal system-on-chip (SoC) devices. It overcomes the parasitic inductance problem of on-chip capacitor decoupling. The effect of the proposed decoupling circuit is not limited by parasitic fine impedance. A 0.13-/spl mu/m CMOS test chip showed that substrate noise at frequencies from 40 MHz to 1 GHz was incrementally suppressed by sequentially activating three of the proposed circuits in parallel. The power dissipation of each circuit was 3.3 mW at a 1.0-V power supply. The test chip measurement showed that the proposed decoupling reduced crosstalk by 31% at 200 MHz, whereas it was reduced by 4.4% with capacitor decoupling. This 7:1 ratio, or 17 dB, corresponds to the gain of the opamp. Design of the opamp and its feedback loop for active decoupling is simple, making the opamp useful for SoC applications.     

Markedly compressible behaviors of gellan hydrogels in a constrained geometry at ultraslow strain rates

The fracture behaviors of gellan hydrogels under compression remarkably depend on the strain rate as well as the boundary conditions for lateral expansion. In the geometry with no constraint for lateral expansion (conventional uniaxial compression), the gels rupture at relatively small strains independently of the compression rates. In contrast, when the gels are compressed extremely slowly (at a strain rate of ca. 10⁻⁵ s⁻¹) in the geometry prohibiting the lateral expansion at their top and bottom surfaces, they are remarkably compressible down to 2% of the initial height without macroscopic fracture and they are accompanied by a large amount of water release. In such markedly compressed gels, many microscopic cracks are formed around the central layer, where strain concentration occurs due to the nonuniform deformation arising from the constrained geometry. In the highly compressible case, the formation of macroscopic cracks is prevented by the localization of microscopic cracks as well as the enhancement in mechanical toughness by a significant increase in polymer concentration due to water release.