自己励起型状態空間モデルを用いた月経周期解析

Open House, ISM in Tachikawa, 2016.6.17統計数理研究所オープンハウス（立川）、H28.6.17ポスター発

月経周期の二相性を考慮した自己閾値型状態空間モデリング

Open House, ISM in Tachikawa, 2017.6.16統計数理研究所オープンハウス（立川）、H29.6.16ポスター発

ニワトリ雛の強化学習モデル：報酬が不確実な場合の選択行動

Open House, ISM in Tachikawa, 2015.6.19統計数理研究所オープンハウス（立川）、H27.6.19ポスター発

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

NADPH Oxidase 2-Derived Reactive Oxygen Species Mediate FFAs-Induced Dysfunction and Apoptosis of β-Cells via JNK, p38 MAPK and p53 Pathways

Dysfunction of β-cell is one of major characteristics in the pathogenesis of type 2 diabetes. The combination of obesity and type 2 diabetes, characterized as ‘diabesity’, is associated with elevated plasma free fatty acids (FFAs). Oxidative stress has been implicated in the pathogenesis of FFA-induced β-cell dysfunction. However, molecular mechanisms linking between reactive oxygen species (ROS) and FFA-induced β-cell dysfunction and apoptosis are less clear. In the present study, we test the hypothesis that NOX2-derived ROS may play a critical role in dysfunction and apoptosis of β-cells induced by FFA. Our results show that palmitate and oleate (0.5 mmol/L, 48 h) induced JNK activation and AKT inhibition which resulted in decreased phosphorylation of FOXO1 following nuclear localization and the nucleocytoplasmic translocation of PDX-1, leading to the reducing of insulin and ultimately dysfunction of pancreatic NIT-1 cells. We also found that palmitate and oleate stimulated apoptosis of NIT-1 cells through p38MAPK, p53 and NF-κB pathway. More interestingly, our data suggest that suppression of NOX2 may restore FFA-induced dysfunction and apoptosis of NIT-1 cells. Our findings provide a new insight of the NOX2 as a potential new therapeutic target for preservation of β-cell mass and function

Lysophosphatidic acid and sphingosine-1-phosphate promote morphogenesis and block invasion of prostate cancer cells in three-dimensional organotypic models

Normal prostate and some malignant prostate cancer (PrCa) cell lines undergo acinar differentiation and form spheroids in three-dimensional (3-D) organotypic culture. Acini formed by PC-3 and PC-3M, less pronounced also in other PrCa cell lines, spontaneously undergo an invasive switch, leading to the disintegration of epithelial structures and the basal lamina, and formation of invadopodia. This demonstrates the highly dynamic nature of epithelial plasticity, balancing epithelial-to-mesenchymal transition against metastable acinar differentiation. This study assessed the role of lipid metabolites on epithelial maturation. PC-3 cells completely failed to form acinar structures in delipidated serum. Adding back lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) rescued acinar morphogenesis and repressed invasion effectively. Blocking LPA receptor 1 (LPAR1) functions by siRNA (small interference RNA) or the specific LPAR1 inhibitor Ki16425 promoted invasion, while silencing of other G-protein-coupled receptors responsive to LPA or S1P mainly caused growth arrest or had no effects. The G-proteins Gα12/13 and Gαi were identified as key mediators of LPA signalling via stimulation of RhoA and Rho kinases ROCK1 and 2, activating Rac1, while inhibition of adenylate cyclase and accumulation of cAMP may be secondary. Interfering with these pathways specifically impeded epithelial polarization in transformed cells. In contrast, blocking the same pathways in non-transformed, normal cells promoted differentiation. We conclude that LPA and LPAR1 effectively promote epithelial maturation and block invasion of PrCa cells in 3-D culture. The analysis of clinical transcriptome data confirmed reduced expression of LPAR1 in a subset of PrCa's. Our study demonstrates a metastasis-suppressor function for LPAR1 and Gα12/13 signalling, regulating cell motility and invasion versus epithelial maturation

Sympatric divergence of risk sensitivity and diet menus in three species of tit

Divergent diet menus could cause sympatric divergence of risk sensitivity; however, evidence is not yet available for the functional link between diet menu and risk sensitivity. We investigated risk sensitivity (measured as the discount intensity for probabilistic rewards) and diet menu (insectivory and granivory) among three sympatric species of tits (family Paridae): varied tits, Poecile varius, marsh tits, Poecile palustris, and great tits, Parus major, which form mixed-species foraging flocks in Japan. Binary choice tests, offering rewards of differing amount and probability, were conducted in the laboratory. Great tits and marsh tits were found to be risk prone (and more insectivorous), whereas varied tits were risk averse (and more granivorous). Diet menus were examined in the laboratory using behavioural titration tests between sunflower seeds and mealworms. The results of these tests were similar to patterns of food exploitation determined using stable isotope analysis (δ13C and δ15N contents) of blood samples from birds collected in the wild. Possibly, the dominant varied tits drove the other two species of tits towards different diet menus and unusually high risk proneness. In future, we should examine whether different interspecies interactions cause different risk sensitivity in other geographical environments

Subjective value of risky foods for individual domestic chicks: a hierarchical Bayesian model

For animals to decide which prey to attack, the gain and delay of the food item must be integrated in a value function. However, the subjective value is not obtained by expected profitability when it is accompanied by risk. To estimate the subjective value, we examined choices in a cross-shaped maze with two colored feeders in domestic chicks. When tested by a reversal in food amount or delay, chicks changed choices similarly in both conditions (experiment 1). We therefore examined risk sensitivity for amount and delay (experiment 2) by supplying one feeder with food of fixed profitability and the alternative feeder with high- or low-profitability food at equal probability. Profitability varied in amount (groups 1 and 2 at high and low variance) or in delay (group 3). To find the equilibrium, the amount (groups 1 and 2) or delay (group 3) of the food in the fixed feeder was adjusted in a total of 18 blocks. The Markov chain Monte Carlo method was applied to a hierarchical Bayesian model to estimate the subjective value. Chicks undervalued the variable feeder in group 1 and were indifferent in group 2 but overvalued the variable feeder in group 3 at a population level. Re-examination without the titration procedure (experiment 3) suggested that the subjective value was not absolute for each option. When the delay was varied, the variable option was often given a paradoxically high value depending on fixed alternative. Therefore, the basic assumption of the uniquely determined value function might be questioned