Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults

An increasing number of patients have medical conditions with altered host immunity or that require immunosuppressive medications. While immunosuppression is associated with increased risk of infection, the precise effect of immunosuppression on innate immunity is not well understood. We studied monocyte Toll-like receptor (TLR) expression and cytokine production in 137 patients with autoimmune diseases who were maintained on immunosuppressive medications and 419 non-immunosuppressed individuals.Human peripheral blood monocytes were assessed for surface expression of TLRs 1, 2, and 4. After incubation with TLR agonists, in vitro production of the cytokines IL-8, TNFalpha, and MIF were measured by ELISA as a measure of TLR signaling efficiency and downstream effector responsiveness. Immunosuppressed patients had significantly higher TLR4 surface expression when compared to non-immunosuppressed adults (TLR4 %-positive 70.12+/-2.28 vs. 61.72+/-2.05, p = 0.0008). IL-8 and TNF-alpha baseline levels did not differ, but were significantly higher in the autoimmune disease group following TLR stimulation. By contrast, baseline MIF levels were elevated in monocytes from immunosuppressed individuals. By multivariable analyses, IL-8 and TNFalpha, but not MIF levels, were associated with the diagnosis of an underlying autoimmune disease. However, only MIF levels were significantly associated with the use of immunosuppressive medications.Our results reveal that an enhanced innate immune response is a feature of patients with autoimmune diseases treated with immunosuppressive agents. The increased risk for infection evident in this patient group may reflect a dysregulation rather than a simple suppression of innate immunity

Evaluation of larval quality of viviparous scorpionfish Sebastiscus marmoratus

The aim of this study was to develop an acute test for larval quality in the viviparous scorpionfish Sebastiscus marmoratus. Rearing experiments until day 13 post parturition were conducted to investigate the survival of larvae for 13 different batches, and tolerance to starvation of larvae was examined and expressed by the survival activity index (SAI). The morphological characters, enzyme activity, and swimming behavior of larvae on day 0 and 1 were also observed, followed by the correlation analysis between SAI. Larvae with high SAI (?26) showed significantly higher survival on day 13 than larvae with low SAI, which confirmed that SAI is a reliable index that can be used to evaluate larval quality, similar to the former findings. The esterase activity (r = -0.713, P < 0.01), swim frequency (r = -0.735, P < 0.01) and swimming speed (r = -0.588, P < 0.05) of larvae on day 0 were significantly and negatively correlated with SAI. It was concluded that enzyme activity and behavioral characters of larvae just after parturition can be a real-time index for evaluating the larval quality of this species

Insulated gate and surface passivation structures for GaN-based power transistors

Recent years have witnessed GaN-based devices delivering their promise of unprecedented power and frequency levels and demonstrating their capability as an able replacement for Si-based devices. High-electron-mobility transistors (HEMTs), a key representative architecture of GaN-based devices, are well-suited for high-power and high frequency device applications, owing to highly desirable III-nitride physical properties. However, these devices are still hounded by issues not previously encountered in their more established Si- and GaAs-based devices counterparts. Metal–insulator–semiconductor (MIS) structures are usually employed with varying degrees of success in sidestepping the major problematic issues such as excessive leakage current and current instability. While different insulator materials have been applied to GaN-based transistors, the properties of insulator/III-N interfaces are still not fully understood. This is mainly due to the difficulty of characterizing insulator/AlGaN interfaces in a MIS HEMT because of the two resulting interfaces: insulator/AlGaN and AlGaN/GaN, making the potential modulation rather complicated. Although there have been many reports of low interface-trap densities in HEMT MIS capacitors, several papers have incorrectly evaluated their capacitance–voltage (C–V) characteristics. A HEMT MIS structure typically shows a 2-step C–V behavior. However, several groups reported C–V curves without the characteristic step at the forward bias regime, which is likely to the high-density states at the insulator/AlGaN interface impeding the potential control of the AlGaN surface by the gate bias. In this review paper, first we describe critical issues and problems including leakage current, current collapse and threshold voltage instability in AlGaN/GaN HEMTs. Then we present interface properties, focusing on interface states, of GaN MIS systems using oxides, nitrides and high-κ dielectrics. Next, the properties of a variety of AlGaN/GaN MIS structures as well as different characterization methods, including our own photo-assisted C–V technique, essential for understanding and developing successful surface passivation and interface control schemes, are given in the subsequent section. Finally we highlight the important progress in GaN MIS interfaces that have recently pushed the frontier of nitride-based device technology

Tumor-derived interleukin-10 as a prognostic factor in stage III patients undergoing adjuvant treatment with an autologous melanoma cell vaccine.

OBJECTIVES: Interleukin-10 (IL-10) downregulates T-cell-mediated immune responses. We studied the association between IL-10 production by freshly isolated melanoma cell suspensions in vitro and overall survival in patients undergoing adjuvant treatment with a vaccine prepared from the same autologous melanoma cells modified with a hapten, dinitrophenyl (DNP). METHODS: Forty-four patients with cutaneous melanoma (29 stage III and 15 stage IV) were prospectively evaluated. Tumor cells were extracted from metastatic deposits for production of DNP-modified autologous melanoma cell vaccine. Small aliquots of the melanoma cell suspensions were separated prior to vaccine processing and cultured overnight for IL-10 production. Based on a blind assessment of the distribution of IL-10 levels in the culture supernatants, a cutoff of 200 pg/ml was used to define high versus low IL-10 producers. Cox regression model was used for multivariate analysis. Overall survival was calculated using the Kaplan-Meier method, and survival curves were compared with the log-rank test. RESULTS: Out of 44 patients, 29 were low and 15 were high IL-10 producers. The median OS was significantly worse for high compared with low IL-10 producers (10.5 months vs. 42 months; P = 0.022). In stage III patients, the multivariate hazard ratio for high versus low IL-10 producers was 2.92 (95% CI, 1.04-8.20; P = 0.041). The corresponding hazard ratio in stage IV patients was 0.92 (95% CI, 1.04-8.20; P = 0.888). CONCLUSIONS: High IL-10 production in the tumor microenvironment could be a determinant of clinical outcomes in stage III melanoma patients receiving autologous melanoma cell vaccine

The distance ecological model to support self/collaborative-learning in the internet environment

With the rapid development of information technology, it is widely accepted that computer and information communication literacy has become extremely important, and is the main new ability required from teachers everywhere. Therefore, for enhancing their teaching skills and information literacy about the Internet environment with multimedia, a new teachers' education framework is necessary. The purpose of the study, is to propose and develop a distance educational system, RAPSODY, which is a school-based curriculum development and training system. In this environment, a teacher can learn subject contents, teaching ways, and evaluation methods of the students' learning activities, related to the new subject called "Information", via an Internet based self-training system. The authors describe the structure, function and mechanism of the distance educational system based on the Distance Ecological Model, in order to realize the above-mentioned goal, and then describe the educational meaning of this model in consideration of the new learning ecology, which is based on multi-modality and new learning situations and form

Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis

AIMS—To determine whether macrophage migration inhibitory factor (MIF) levels were increased in sera of the patients with iridocyclitis.
METHODS—Sera were obtained from 41 patients with acute iridocyclitis, 13 patients with chronic iridocyclitis, and 44 healthy control subjects. MIF levels were determined by a human MIF ELISA.
RESULTS—The average levels of MIF in the sera of patients with both acute and chronic iridocyclitis were significantly higher than that of healthy subjects.
CONCLUSION—Uveitis induces the elevation of serum MIF, which may affect various inflammatory symptoms in uveitis.


A cooperative linkage between University and industry via an internet distance education system

The Industry and University cooperation program is a project of the Japanese Ministry of Education (Mombusho). The target objective of this program is the harmonization of university level educational research, society practice and practical business. The University of Electro-Communications has been appointed by Mombusho to fulfill some specific parts of this program. In this paper we report our experience with the introduction of this program, its framework, settings, actual implementation and preliminary findings. The problems encountered are discussed together with a number of solutions to assist good practice in the building of such an applied educational program