The Stability Balloon for Two-dimensional Vortex Ripple Patterns

Patterns of vortex ripples form when a sand bed is subjected to an oscillatory fluid flow. Here we describe experiments on the response of regular vortex ripple patterns to sudden changes of the driving amplitude a or frequency f. A sufficient decrease of f leads to a "freezing" of the pattern, while a sufficient increase of f leads to a supercritical secondary "pearling" instability. Sufficient changes in the amplitude a lead to subcritical secondary "doubling" and "bulging" instabilities. Our findings are summarized in a "stability balloon" for vortex ripple pattern formation.Comment: 4 pages, 5 figure

Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries

Capsaicin, a pungent constituent from red chilli peppers, activates sensory nerve fibres via transient receptor potential vanilloid receptors type 1 (TRPV1) to release neuropeptides like calcitonin gene-related peptide (CGRP) and substance P. Capsaicin-sensitive nerves are widely distributed in human and porcine vasculature. In this study, we examined the mechanism of capsaicin-induced relaxations, with special emphasis on the role of CGRP, using various pharmacological tools. Segments of human and porcine proximal and distal coronary arteries, as well as cranial arteries, were mounted in organ baths. Concentration response curves to capsaicin were constructed in the absence or presence of the CGRP receptor antagonist olcegepant (BIBN4096BS, 1 μM), the neurokinin NK1 receptor antagonist L-733060 (0.5 μM), the voltage-sensitive calcium channel blocker ruthenium red (100 μM), the TRPV1 receptor antagonist capsazepine (5 μM), the nitric oxide synthetase inhibitor Nω-nitro-l-arginine methyl ester HCl (l-NAME; 100 μM), the gap junction blocker 18α-glycyrrhetinic acid (10 μM), as well as the RhoA kinase inhibitor Y-27632 (1 μM). Further, we also used the K+ channel inhibitors 4-aminopyridine (1 mM), charybdotoxin (0.5 μM) + apamin (0.1 μM) and iberiotoxin (0.5 μM) + apamin (0.1 μM). The role of the endothelium was assessed by endothelial denudation in distal coronary artery segments. In distal coronary artery segments, we also measured levels of cyclic adenosine monophosphate (cAMP) after exposure to capsaicin, and in human segments, we also assessed the amount of CGRP released in the organ bath fluid after exposure to capsaicin. Capsaicin evoked concentration-dependent relaxant responses in precontracted arteries, but none of the above-mentioned inhibitors did affect these relaxations. There was no increase in the cAMP levels after exposure to capsaicin, unlike after (exogenously administered) α-CGRP. Interestingly, there were significant increases in CGRP levels after exposure to vehicle (ethanol) as well as capsaicin, although this did not induce relaxant responses. In conclusion, the capsaicin-induced relaxations of the human and porcine distal coronary arteries are not mediated by CGRP, NK1, NO, vanilloid receptors, voltage-sensitive calcium channels, K+ channels or cAMP-mediated mechanisms. Therefore, these relaxant responses to capsaicin are likely to be attributed to a non-specific, CGRP-independent mechanism

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Cgrp Uptake into Perivascular Capsaicin-Sensitive Nerve Terminals

Specific mechanisms, providing reuptake of cathecholamine and amino acid neurotransmitters (e.g., serotonin and glutamate) into cells of the central nervous system are well known, whereas neuronal uptake of neuropeptides have not previously been reported

[[alternative]]An action research of using flipped classroom to learn mathematics and attitudes on setting one-variable linear equation for junior high school students

碩士[[abstract]]在傳統的教學環境，學生多是單向接收教師所傳達的訊息，較缺乏雙向互動的機會，且數學學習偏重事實知識的記憶，故本研究主要是探討運用翻轉教室對於國中學生數學學習成效與學習態度之影響。 本研究採行動研究法進行二次的循環教學設計方案，以研究者任教臺北市某完全中學國中七年級班級，共26人為研究對象，進行一元一次方程式的學習。希望透過翻轉教室的教學設計、均一教育平台的學習工具、學習成就評量、學習態度量表及教學質性記錄等方式進行資料蒐集與分析，以了解翻轉教室的學習歷程，及對學生學習成效與學習態度的影響，並進行教學反思。 本研究發現自主學習讓每一位學生掌握自己的自主學習步調，從中獲得學習的成就感，使學生學習能主動積極。課堂上廣泛的參與活動與解決問題，使學生對數學的學習內容有更深入的理解與延伸應用，達到學習遷移的目的。教學活動能在以學習者為中心，透過教師與學生的雙向的互動過程，引導學生思辨討論，提升學生的學習層次。故運用翻轉教室進行教學能有效提升國中學生學習數學成效，且在數學學習態度量表的「學習習慣」向度達統計上的顯著差異，特別是學習低成就學生有顯著提升。而在「學習慾望」、「自我認識」、「學習方法」、「學習計劃」與「學習過程」等，雖未達統計上的顯著差異，但平均數都有上升。 翻轉教室的課前自主學習，讓學生在有效學習下，利用均一教育平台取代傳統的課後練習作業，減輕學習數學的負擔，並培養學生學會如何學習，以提升教育品質。翻轉教室的課堂活動，能兼顧學習成效差異的學生，讓被動學習的學生都能共同參與課堂活動，實現成就每一個孩子。 基於上述的研究發現與結論，本研究提供若千建議供國中教師及研究者在未來進行翻轉教室及相關研究之參考。[[abstract]]In the traditional teaching environment, students received more one-way information from their teachers and they had less opportunities of two-way interactions. In addition, mathematics learning emphasized on the memories of factual knowledge. Therefore, the purpose of this study is to probe into the influence of the junior high school students’ mathematics learning effects and attitudes with the Flipped classroom. This research design used the two-cycle model of action research to improve instructional programs. The subjects were 26 seventh grade students taught by the researcher in junior high school in Taipei, learning One-variable Linear Equation. The researcher collected and analyzed the information about the instructional design with the Flipped classroom, the learning platform of Junyi Academy, the assessment of the students’ learning achievements, the scale of the students’ learning attitude and the qualitative teaching record to get the points about the learning process with the Flipped classroom, the influence of the students’ learning effect and attitude and teaching reflection. The research indicates that self-learning makes students not only master their own learning steps, but also get learning achievements, and thus they would like to learn mathematics more positive than before. Extensive practice of class activities and problem solution makes the students have deeper understanding and extensive application of math learning to accomplish learning transference. Teaching activities with learner-centered aims and emphasizing the interaction between the teacher and students can lead students to think and then promote students’ learning level. Therefore, teaching with the Flipped classroom can effectively promote junior high school students’ math learning effects and make the dimension of learning habits of math-learning attitude scale achieve significantly different on the statics, particularly for underachievers in math . However, the dimensions of learning motivation, self-awareness, learning methods, learning plans and learning process were not significantly different on the statics, but the average of the five dimensions is upgraded. In the Flipped classroom, students’ effective self-learning using Junyi Academy before class replaces the general handwriting exercises after class. This can not only lighten students burden of learning math but also teach them a way to learn by themselves, which promote education quality at the same time. The Flipped Classroom can give consideration to the differences between students’ learning effectiveness, so that passive learners can also participate in classroom activities. It can make students more successful. According to the finding and conclusion of the research, some suggestions are proposed to be the reference for the future researchers and the junior high school math teachers.[[tableofcontents]]目次 中文摘要 i 英文摘要 iii 目次 v 表次 vii 圖次 ix 第一章 緒論 1 第一節 研究背景與動機 1 第二節 研究目的與待答問題 6 第三節 名詞釋義 6 第四節 研究範圍與研究限制 8 第五節 研究貢獻 9 第二章 文獻探討 11 第一節 數學代數學習 11 第二節 翻轉教室 20 第三節 大規模開放式線上課程 29 第三章 研究方法 37 第一節 研究架構與流程 37 第二節 研究場域與對象 45 第三節 研究工具 50 第四節 資料蒐集與分析 69 第四章 研究結果與討論 73 第一節 翻轉教室的學習歷程 73 第二節 翻轉教室對於學習的影響 97 第三節 翻轉教室的反思 118 第五章 結論與建議 121 第一節 結論 121 第二節 建議 124 參考文獻 129 壹、中文部分 129 貳、外文部分 133 附錄 137 附錄一 第一階段課堂作業（學習單） 137 附錄二 第二階段課堂作業（學習單） 143 附錄三 第一階段形成性評量 149 附錄四 第二階段形成性評量 151 附錄五 總結性評量 153 附錄六 數學學習態度量表 155 附錄七 教師觀察紀錄單 157 附錄八 觀察教師回饋單 158 附錄九 半結構式訪談大綱 159 附錄十 均一教育平台使用統計表 160 表次 表2-1-1 一元一次方程式的相關研究 15 表2-1-2 學習態度向度表 17 表2-1-3 學習態度量表相關研究 18 表2-2-1 翻轉教室與傳統教學比較 22 表2-3-1 Udacity、Coursera與edX三個線上教育機構一覽表 30 表3-2-1 研究對象學習表現與學習態度概述 47 表3-2-2 研究對象的電腦與網路之使用情形 49 表3-3-1 第一次行動研究課程主要內容與教學目標 50 表3-3-2 第二次行動研究課程主要內容與教學目標 51 表3-3-4 翻轉教室教學活動設計 53 表3-3-5 均一教育平台功能簡介一覽表 56 表3-3-6 均一教育平台學習影片內容檢核結果一覽表 61 表3-3-7 均一教育平台練習試題檢核結果一覽表 65 表3-3-8 總結性評量試題雙向細目分析表 66 表3-3-9 學習態度向度意涵與對應題數及題號 67 表3-4-1 三角交叉矩陣圖 71 表3-4-2 資料編碼系統表 72 表4-1-1 第一階段的課程進度與課程大網 74 表4-1-2 第一階段均一教育平台使用時間統計表 77 表4-1-3 第一階段均一教育平台使用天數統計表 77 表4-1-4 第一階段學習單錯誤類型一覽表 79 表4-1-5 第二階段的課程進度與課程大網 87 表4-1-6 第二階段均一教育平台使用時間統計表 90 表4-1-7 第二階段均一教育平台使用天數統計表 90 表4-1-8 第二階段學習單錯誤類型一覽表 93 表4-2-1 第一階段均一教育平台課程單元熟悉程度統計表 99 表4-2-2 第一階段評量各學習單元平均答對率 100 表4-2-3 第二階段均一教育平台課程單元熟悉程度統計表 103 表4-2-4 第二階段評量各學習單元平均答對率 104 表4-2-5 定期考查各學習單元全班平均答對率 108 表4-2-6 定期考查班級平均成績一覽表 109 表4-2-7 全部學生數學學習態度量表各向度前、後測之統計分析（n=26） 110 表4-2-8 高分組數學學習態度量表各向度前、後測之統計分析（n=13） 111 表4-2-9 低分組數學學習態度量表各向度前、後測之統計分析（n=13） 111 圖次 圖2-2-1 以Bloom認知領域教學目標與修訂版解讀翻轉教室成效 23 圖2-3-1 可汗學院網頁畫面 31 圖2-3-2 可汗學院網頁課程 31 圖3-1-1 研究架構圖 38 圖3-1-2 研究流程圖 39 圖3-1-3 學生分組情形分佈圖 42 圖3-2-1 教室環境及座位平面示意圖 46 圖3-3-1 均一教育平台課程對照網頁 60 圖4-1-1 第一階段均一教育平台學習影片與練習技能數量統計圖 78 圖4-1-2 第二階段均一教育平台學習影片與練習技能數量統計圖 91 圖4-2-1 第一階段均一教育平台練習技能表現長條圖 98 圖4-2-2 第二階段均一教育平台練習技能表現統計圖 102 圖4-2-3 均一教育台兩階段課程範圍的學生技能熟悉比率長條圖 106 圖4-2-4 均一教育台兩階段課程單元的技能熟悉比率長條圖 107 圖4-3-1 均一教育平台兩階段使用時間長條圖 118 圖4-3-2 均一教育平台兩階段使用天數折線圖 119[[note]]學號: 799740153, 學年度: 10