Design of fuzzy system by NNs and realization of adaptability

The issue of designing and tuning fuzzy membership functions by neural networks (NN's) was started by NN-driven Fuzzy Reasoning in 1988. NN-driven fuzzy reasoning involves a NN embedded in the fuzzy system which generates membership values. In conventional fuzzy system design, the membership functions are hand-crafted by trial and error for each input variable. In contrast, NN-driven fuzzy reasoning considers several variables simultaneously and can design a multidimensional, nonlinear membership function for the entire subspace

Paired Comparisons-based Interactive Differential Evolution

We propose Interactive Differential Evolution (IDE) based on paired comparisons for reducing user fatigue and evaluate its convergence speed in comparison with Interactive Genetic Algorithms (IGA) and tournament IGA. User interface and convergence performance are two big keys for reducing Interactive Evolutionary Computation (IEC) user fatigue. Unlike IGA and conventional IDE, users of the proposed IDE and tournament IGA do not need to compare whole individuals each other but compare pairs of individuals, which largely decreases user fatigue. In this paper, we design a pseudo-IEC user and evaluate another factor, IEC convergence performance, using IEC simulators and show that our proposed IDE converges significantly faster than IGA and tournament IGA, i.e. our proposed one is superior to others from both user interface and convergence performance points of view

Ergonomic Chair Design by Fusing Qualitative and Quantitative Criteria using Interactive Genetic Algorithms

This paper emphasizes the necessity of formally bringing qualitative and quantitative criteria of ergonomic design together, and provides a novel complementary design framework with this aim. Within this framework, different design criteria are viewed as optimization objectives; and design solutions are iteratively improved through the cooperative efforts of computer and user. The framework is rooted in multi-objective optimization, genetic algorithms and interactive user evaluation. Three different algorithms based on the framework are developed, and tested with an ergonomic chair design problem. The parallel and multi-objective approaches show promising results in fitness convergence, design diversity and user satisfaction metrics

Seasonal changes of carbon and nitrogen stable isotope ratios for dominant species: chironomid larvae, phytoplankton, and benthic diatom inhabiting strongly acidic Lake Katanuma

Lake Katanuma is a colcanic, strongly acidic lake (average pH of 2.2), located in Miyagi prefecture, Japan. Only a few spieccies are found in Katanuma; Chironomus acerbiphis larvae as benthic invertebrate, Pinnularia baunii as benthic diatom, and Chlamydomonas acidophila as phytoplnkton. We tried analyzing seasonal changes of carbon and nitrogen stable isotope raios foethese spicies in Lake Katanuma. Food souece analysis by isotope ratios clearly showed main food source for Chironomus acerbiphilus larvae was P.braunii (benthic diatom). δ1C values of P.braunii varied seasonally, while those of POM (mainly phytoplankton) remained fairly stable. The difference of stable isotope ratios in these orfanisms discussed.Article信州大学山地水環境教育研究センター研究報告 2: 25-28(2004)departmental bulletin pape

FKBP5 regulation on anti-PD-1 therapy

Background. Antitumor therapies targeting programmed cell death-1 (PD-1) or its ligand-1 (PD-L1) are used in various cancers. However, in glioblastoma (GBM), the expression of PD-L1 varies between patients, and the relationship between this variation and the efficacy of anti-PD-1 antibody therapy remains unclear. High expression levels of PD-L1 affect the proliferation and invasiveness of GBM cells. As COX-2 modulates PD-L1 expression in cancer cells, we tested the hypothesis that the COX-2 inhibitor celecoxib potentiates anti-PD-1 antibody treatment via the downregulation of PD-L1. Methods. Six-week-old male C57BL/6 mice injected with murine glioma stem cells (GSCs) were randomly divided into four groups treated with vehicle, celecoxib, anti-PD-1 antibody, or celecoxib plus anti-PD-1 antibody and the antitumor effects of these treatments were assessed. To verify the mechanisms underlying these effects, murine GSCs and human GBM cells were studied in vitro. Results. Compared with that with each single treatment, the combination of celecoxib and anti-PD-1 antibody treatment significantly decreased tumor volume and prolonged survival. The high expression of PD-L1 was decreased by celecoxib in the glioma model injected with murine GSCs, cultured murine GSCs, and cultured human GBM cells. This reduction was associated with post-transcriptional regulation of the co-chaperone FK506-binding protein 5 (FKBP5). Conclusions. Combination therapy with anti-PD-1 antibody plus celecoxib might be a promising therapeutic strategy to target PD-L1 in glioblastoma. The downregulation of highly-expressed PD-L1 via FKBP5, induced by celecoxib, could play a role in its antitumor effects

Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma

Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C–C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin+ stem cells, CD16+ or CD163+ macrophages and Iba-1+ microglia. In GSCs, celecoxib inhibited Ccl2 and Cxcr3 expression in a nuclear factor-kappa B-dependent manner but not Ccr2 and CxcL10. Moreover, Ccl2 silencing resulted in decreased GSC viability. These results suggest that celecoxib-mediated regulation of the CCL2/CCR2 and CXCL10/ CXCR3 axes may partially contribute to glioma-specific antitumor effects