Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes

AbstractObjectivesThis study was designed to examine the myocardial protective effect of leukocyte-depleted terminal blood cardioplegia in association with nitric oxide and peroxynitrite production, especially for patients undergoing prolonged aortic crossclamping.MethodsFifty-four patients (34 men, 20 women, mean age 56.7 ± 12.7 years) undergoing aortic valve replacement were randomly allocated to one of two groups; group LDTC (n = 27) received 10 minutes of leukocyte-depleted terminal blood cardioplegic solution, and group CONT (n = 27) served as controls. Each group was subdivided into 2 groups: aortic crossclamping for less than 120 minutes in groups LDTC-S (n = 13) and CONT-S (n = 14); aortic crossclamping for 120 minutes or more in groups LDTC-L (n = 14) and CONT-L (n = 13).ResultsAfter aortic unclamping, group LDTC-L showed higher incidence of spontaneous defibrillation (78.6% vs 30.8%, P = .0213), higher plasma nitrate + nitrite in the coronary sinus effluent (32.5 ± 4.1 vs 28.7 ± 3.0 μmol/L, P = .0013), lower differences between coronary sinus effluent and arterial blood in the percentage ratio of nitrotyrosine to tyrosine (myocardium-derived peroxynitrite; 2.987% ± 0.576% vs 3.951% ± 0.952%, P = .0036), and plasma polymorphonuclear-elastase (113.9 ± 21.3 vs 155.5 ± 41.6 μg/L, P = .0029) and malondialdehyde (2.75 ± 0.67 vs 4.02 ± 0.96 μmol/L, P = .0005) than group CONT did. Postoperatively, group LDTC-L showed lower human-heart fatty acid–binding protein (111.4 ± 25.2 vs 156.4 ± 38.6 IU/L, P = .0013), lower creatine kinase–muscle and brain (19.2 ± 4.7 vs 24.8 ± 6.5 IU/L, P = .0120), and smaller requirement of catecholamine (5.44 ± 2.29 vs 8.45 ± 3.42 μg · kg−1 · min−1, P = .0122). There were no significant differences in these parameters between groups LDTC-S and CONT-S.ConclusionsThis study demonstrated that leukocyte-depleted terminal blood cardioplegia provided superior myocardial protective effects and regulated myocardial-derived nitric oxide and peroxynitrite production only for patients undergoing aortic crossclamping for more than 120 minutes. The results suggest that prolonged aortic crossclamping deteriorates the tolerance to leukocyte-mediated myocardial injury accompanied by endothelial dysfunction associated with nitric oxide and peroxynitrite production

Making Gaming Instructional Material for Exploration Activitiesand Year Plan of Information I Based on New Backward Design Method

P(論文)1998 ～ 9 年の学習指導要領改訂で，教科学習の成果を統合して問題解決に取り組むための「総合的な学習の時間」が導入され，各学校段階で必須になった．しかし，その機会を十分に活用し，成果をあげることはできていない．筆者は，SDGsの達成に関わる政策評価を「総合的な学習の時間」の課題とし，それに役立つ準備学習を各教科で行うという「新逆向き設計」手法を提案している．これによって教科カリキュラムを再構成することが成功の鍵だと考えているからである．新逆向き設計では，教科との接続の鍵になる教科の探究活動の設計が鍵になる．筆者は，湖沼の水質改善を共通題材にして，既に，数学や理科で探求活動の導入用ゲーミング教材を開発してきた．本稿では，教科間の連携と役割分担を明確にするために，同じ題材で情報科の「総合演習」導入用ゲーミング教材を設計する．合わせて，教科の通常授業の見直しを行う観点から，総合演習との連携を図った年間指導計画も考察する．departmental bulletin pape

Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-κB activation

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) is associated with the development of adult T-cell leukemia (ATL). HTLV-1 encoded Tax1 oncoprotein activates the transcription of genes involved in cell growth and anti-apoptosis through the NF-κB pathway, and is thought to play a critical role in the pathogenesis of ATL. While Tax1 expression is usually lost or minimal in ATL cells, these cells still show high constitutive NF-κB activity, indicating that genetic or epigenetic changes in ATL cells induce activation independent of Tax1. The aim of this study was to identify the molecules responsible for the constitutive activation of NF-κB in ATL cells using a retroviral functional cloning strategy. RESULTS: Using enhanced green fluorescent protein (EGFP) expression and blasticidin-resistance as selection markers, several retroviral cDNA clones exhibiting constitutive NF-κB activity in Rat-1 cells, including full-length CD30, were obtained from an ATL cell line. Exogenous stable expression of CD30 in Rat-1 cells constitutively activated NF-κB. Elevated expression of CD30 was identified in all ATL lines examined, and primary ATL cells from a small number of patients (8 out of 66 cases). CONCLUSION: Elevated CD30 expression is considered one of the causes of constitutive NF-κB activation in ATL cells, and may be involved in ATL development

授業進行支援システムを応用した効果的なマルチメディア教材開発手法

従来から、マルチメディア教材による授業の効果については、多数報告されている。しかし、多様なマルチメディア素材を、教材にどう組み合わせるかということは、基本的に作成者の予測に頼らざるをえなかった。本研究では、学習者の反応を利用しながら、素材の多様な組み合わせを評価し、よりよい教材を作成する方法を検討した。そのために、中山らの授業進行支援システムを応用して、提示した仮教材に対する学習者側の反応をリアルタイムで収集・分析し、ルールに基づいて代替教材を選択・提示する手法を開発した。本手法で作成した教材を修正前の教材と比較評価したところ、学習者の理解度に有意差が見られた。また、本手法で作成した教材を専門家が作成した市販教材と比較評価したところ、学習者の理解度は同等であるとの評価結果が得られた。Many studies have been published on the development of multimedia teaching materials, but most have relied heavily on the conjectures of the authors. Using a learner\u27s response, this study examined how to develop better teaching materials by evaluating the efficiency of various combinations of the materials in question. To accomplish this, we developed a method for making multimedia teaching materials that allowed us to : 1) apply a lesson progress support system; 2) collect and analyze the learner\u27s response to the presented temporary materials in real time; and 3) choose and present substitution materials based on the rules in real time. Based on the response of learner in another experimental class of the same level, we found that a teaching material made by this method was superior to a teaching material not made by this method. By using the teaching material made by this method and comparing it to a teaching material made by a specialist made in the experimental class, equal evaluation brought both of the teaching materials

MR perfusion imaging by alternate slab width inversion recovery arterial spin labeling (AIRASL): a technique with higher signal-to-noise ratio at 3.0 T

Object: To propose a new arterial spin labeling (ASL) perfusion-imaging method (alternate slab width inversion recovery ASL: AIRASL) that takes advantage of the qualities of 3.0 T. Materials and methods: AIRASL utilizes alternate slab width IR pulses for labeling blood to obtain a higher signal-to-noise ratio (SNR). Numerical simulations were used to evaluate perfusion signals. In vivo studies were performed to show the feasibility of AIRASL on five healthy subjects. We performed a statistical analysis of the differences in perfusion SNR measurements between flow-sensitive alternating inversion recovery (FAIR) and AIRASL. Results: In signal simulation, the signal obtained by AIRASL at 3.0 and 1.5 T was 1.14 and 0.85%, respectively, whereas the signal obtained by FAIR at 3.0 and 1.5 T was 0.57 and 0.47%, respectively. In an in vivo study, the SNR of FAIR (3.0 T) and FAIR (1.5 T) were 1.73 ± 0.49 and 1.02 ± 0.20, respectively, whereas the SNRs of AIRASL (3.0 T) and AIRASL (1.5 T) were 3.93 ± 1.65 and 1.34 ± 0.31, respectively. SNR in AIRASL at 3.0 T was significantly greater than that in FAIR at 3.0 T. Conclusion: The most significant potential advantage of AIRASL is its high SNR, which takes advantage of the qualities of 3.0 T. This sequence can be easily applied in the clinical setting and will enable ASL to become more relevant for clinical application. © 2012 ESMRMB.Article in Press エンバーゴ設定 Thesis of Fujiwara, Yasuhiro / 藤原 康博 博士学位論文(金沢大学 / 大学院医薬保健学総合研究科

Polycomb-Mediated Loss of miR-31 Activates NIK-Dependent NF-κB Pathway in Adult T Cell Leukemia and Other Cancers

SummaryConstitutive NF-κB activation has causative roles in adult T cell leukemia (ATL) caused by HTLV-1 and other cancers. Here, we report a pathway involving Polycomb-mediated miRNA silencing and NF-κB activation. We determine the miRNA signatures and reveal miR-31 loss in primary ATL cells. MiR-31 negatively regulates the noncanonical NF-κB pathway by targeting NF-κB inducing kinase (NIK). Loss of miR-31 therefore triggers oncogenic signaling. In ATL cells, miR-31 level is epigenetically regulated, and aberrant upregulation of Polycomb proteins contribute to miR-31 downregulation in an epigenetic fashion, leading to activation of NF-κB and apoptosis resistance. Furthermore, this emerging circuit operates in other cancers and receptor-initiated NF-κB cascade. Our findings provide a perspective involving the epigenetic program, inflammatory responses, and oncogenic signaling

Supurvision of Student Teachers' Research Activities and Collaboration with High Schoolin FY2022 "Exercise of Practical Research on Mathematics/Science Education I/II"

P(論文)本稿では，東京工業大学の教職科目「数学科／理科教育法実践演習Ⅰ」「同Ⅱ」における教育実践研究指導および東京工業大学附属科学技術高等学校との連携の概要を報告する．「同Ⅰ」においては，「総合的な学習の時間」の実践事例から問題点を整理し，新・逆向き設計に基づき，文献研究を行いつつ，SDGs に関する政策評価を問題解決の縦糸・横糸モデルに沿って体験した．また，「数学」では課題学習導入のゲーミング教材を実践し，「理科」では先行研究に基づいた授業実践を行った．後半は「数学Ⅰ」，あるいは「化学基礎」の年間指導計画を作成した．「同Ⅱ」では，「同Ⅰ」を踏まえて「数学」「理科」それぞれで「教授活動ゲーム」システムを用いたゲーミング教材を作成し，附属高校で実践した．ここで得られたログの解析を行い，論文にまとめて発表した．このように今年度の活動を振り返り，今後の指導の改善や，高大連携の強化を探る．departmental bulletin pape

A gravitationally unstable gas disk of a starburst galaxy 12 billion years ago

Submillimeter bright galaxies in the early Universe are vigorously forming stars at ~1000 times higher rate than the Milky Way. A large fraction of stars is formed in the central 1 kiloparsec region, that is comparable in size to massive, quiescent galaxies found at the peak of the cosmic star formation history, and eventually the core of giant elliptical galaxies in the present-day Universe. However, the physical and kinematic properties inside a compact starburst core are poorly understood because dissecting it requires angular resolution even higher than the Hubble Space Telescope can offer. Here we report 550 parsec-resolution observations of gas and dust in the brightest unlensed submillimeter galaxy at z=4.3. We map out for the first time the spatial and kinematic structure of molecular gas inside the heavily dust-obscured core. The gas distribution is clumpy while the underlying disk is rotation-supported. Exploiting the high-quality map of molecular gas mass surface density, we find a strong evidence that the starburst disk is gravitationally unstable, implying that the self-gravity of gas overcomes the differential rotation and the internal pressure by stellar radiation feedback. The observed molecular gas would be consumed by star formation in a timescale of 100 million years, that is comparable to those in merging starburst galaxies. Our results suggest that the most extreme starburst in the early Universe originates from efficient star formation due to a gravitational instability in the central 2 kpc region.Comment: Published in Nature on August 30 2018 (submitted version