Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis

Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis

コーパス日本語学のための言語資源 : 形態素解析用電子化辞書の開発とその応用

千葉大学国立国語研究所国立国語研究所京都高度技術研究所東京大学情報通信研究機構国立国語研究所Chiba UniversityThe National Institute for Japanese LanguageThe National Institute for Japanese LanguageASTEMThe University of TokyoNational Institute of Information and Communications TechnologyThe National Institute for Japanese Languageコーパス日本語学への応用を指向した形態素解析用電子化辞書UniDicを開発した。大規模コーパスに対する形態論情報付与作業には,計算機を用いた形態素解析システムの利用が不可欠であるが,既存の形態素解析システム用辞書には,コーパス日本語学への応用を考える上でさまざまな不都合がある。1つは,単位の認定がある場合には長く,ある場合には短いといった不揃いがあることであり,もう1つは,異表記や異形態に対して同一の見出しが与えられないということである。言語研究で重要な要件となる,このような単位の斉一性や見出しの同一性への対処といったことを中心に,本電子化辞書の設計方針とそれを実装した辞書データベースシステムについて述べる。さらに,この設計の有用性を示すため,表記や語形の変異に関するコーパス分析の事例を紹介する。In this paper, we describe the design and the implementation of an electronic dictionary for morphological analysis, UniDic, which aims particularly at application to Japanese corpus linguistics. It has been indispensable for the development of a large-scale corpus to utilize an automatic morphological analyzer on computer. The existing dictionaries for morphological analyzers, however, reveal lots of problems when used in corpus linguistics, such as unevenness in defining a unit and failure in handling allomorphs and orthographic variants. Our dictionary, in contrast, deals with the uniformity of units and the identity of indexes, which are important requirements for linguistic analysis of corpora. We adopt multi-level definition of word units, consisting of short-, middle-, and long-unit words, and structured representation of indexes, composed of lemma, word form, orthography, and pronunciation. We develop a database system that straight-forwardly implements this design of the dictionary and a friendly user-interface for dictionary builders to be capable of searching and registering entries with grasping the complex structure of the indexes. We also show how this structured representation benefits us in analyzing morphologically annotated corpora, presenting case studies that investigate the variation of word form in spoken language corpus and the variation of orthography in written language corpus

Release of siRNA from Liposomes Induced by Curcumin

Liposomes are a potential carrier of small interfering RNA (siRNA) for drug delivery systems (DDS). In this study, we searched for a molecule capable of controlling the release of siRNA from a certain type of liposomes and found that curcumin could induce the release of siRNA from the liposomes encapsulating siRNA within 30 min. However, the release of siRNA from the liposomes by curcumin showed a unique dose-response (i.e., bell-shaped curve) with a maximal induction at around 60 μg/ml of curcumin. Liposomal lipid compositions and temperatures influenced the efficiency in the release of siRNA induced by curcumin. About 10% of curcumin at a 60 μg/ml dose was incorporated into the liposomes within 30 min under our experimental conditions. Our results suggest a possibility that curcumin is useful in controlling the permeability of liposomes carrying large molecules like siRNA

Improving WFST-based G2P Conversion with Alignment Constraints and RNNLM N-best Rescoring

This work introduces a modified WFST-based multiple to multiple EM-driven alignment algorithm for Graphemeto-Phoneme (G2P) conversion, and preliminary experimental results applying a Recurrent Neural Network Language Model (RNNLM) as an N-best rescoring mechanism for G2P conversion. The alignment algorithm leverages the WFST framework and introduces several simple structural constraints which yield a small but consistent improvement in Word Accuracy (WA) on a selection of standard baselines. The RNNLM rescoring further extends these gains and achieves state-of-the-art performance on four standard G2P datasets. The system is also shown to be significantly faster than existing solutions. Finally, the complete WFST-based G2P framework is provided as an open-source toolkit

Dose-Response Curves of Curcumin/Liposome in Inhibition of Cell Proliferation.

<p>THP-1 (panel A) or RAW264.7 (panel B) cells were cultured for 3 days in the presence of curcumin/liposome (●), curcumin (▲), and control liposomes (○), respectively. After culturing, they were incubated with WST-8 for 3 h to assess viable cells in the culture. Resultant coloring reaction by WST-8 was measured with a plate-reader at the absorbance of 450 nm. In the vertical axis, the absorbance of only the medium was defined as 0%. Symbols in the Figure represent the percentage of absorbance with curucmin or liposomes to that without the test samples. Data represent mean values ± range (bars) in duplicate assays.</p

Effect of In Vivo Administration of Curcumin/Liposome on IL-6 Production from Mouse Peritoneal Cells.

<p>Balb/c mice were injected with thioglycollate 3 days before harvesting peritoneal cells. Curcumin/liposome (filled bars) or control liposomes (gray bars) were injected into the mice 4 or 24 h before harvesting the cells. The harvested cells were cultured for 24 h in the absence (panel A) or presence (panel B) of LPS as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137207#pone.0137207.g004" target="_blank">Fig 4</a>. Blank columns represent IL-6 production in the culture of the peritoneal cells from mice without receiving the injection of liposomes. IL-6 in the culture supernatants were quantified in triplicate assays. Data represent mean values ± standard deviation (bars) in triplicate assays. **indicate that P<0.01 compared to mice injected with control liposomes.</p