1,720,984 research outputs found
Mathematical model development for salmonella transfer during washing and subsequent growth in fresh cut produce
No full textThe causes of most fresh produce outbreaks in U.S. are unknown, but cross contamination during washing or improper storage temperatures during retail storage, distribution or home storage may play a role. The first objective of our research was to integrate and compare published data, published models and data from the ComBase database relevant to Salmonella growth in fresh and fresh-cut produce. The second objective of our research was to develop a cross contamination model that predicts the concentration of contaminated produce and the concentration of non- contaminated produce after washing using literature data. A literature research was conducted to find relevant data on the growth of Salmonella on fresh cut produce. Data for Salmonella growth in a variety of fruit and vegetable products was also extracted from ComBase. Calculated growth rates were converted to square-root growth rates for comparative purposes and analyzed. Four published Salmonella growth models (Koseki and Isobe on iceberg lettuce; Pan and Schaffner on cut tomatoes; Li et al on cut melons; and Sant'Ana et al on lettuce) were compared to the extracted data. The most conservative model (Koseki and Isobe, 2005) was fail-safe for all but 5.5% (6/109) of the extracted data, predicting faster growth that that actually observed. A literature research was conducted to find relevant published data on the cross contamination rates between contaminated produce after wash, wash water and non- contaminated produce after wash. Data were converted to the same units, log transformed, used to create histograms and figures using Microsoft Excel. GInaFit and BestFit software were used to select suitable distributions. The software program @RISK was used to build a risk model. The simulation model predicted that when tomatoes were contaminated at 4 log CFU/tomato, after washing at 100 ppm chlorine, those same tomatoes contained ~1.0 log CFU/tomato, while contaminated cantaloupes contain ~2.8 log CFU/cantaloupe after washing at 0 ppm chlorine. The simulation model also predicted that uncontaminated tomatoes after washing at 0 ppm chlorine with contaminated tomatoes will contain ~ -0.59 log CFU/tomato (or 1 in 4 tomatoes containing ≥ 1 CFU), while uncontaminated cantaloupes after washing at 100 ppm chlorine with contaminated cantaloupes will contain ~ -2.83 log CFU/cantaloupe (or 1 in 676 tomatoes containing ≥ 1 CFU).M.S.Includes bibliographical referencesby Fang-Yu Li
Structure-based Fragment Hopping for Lead Optimization Using Predocked Fragment Database
No full textRegulation of GCM1 Stability by Protein Dephosphorylation
No full textGCM1為於胎盤內特殊表現的轉錄因子，其可調控syncytin膜蛋白的表現，而促進融合滋養層細胞的形成與分化，以維持胎盤構造進行物質交換的重要功能。於細胞內，GCM1活性的調控，可藉由不同層面轉譯後的修飾作用，影響其磷酸化、汎素化及乙烯化的作用程度，而維持GCM1的穩定性和轉錄活性。新近研究已知，當細胞受特定環境刺激，例如：處於缺氧情況下，而活化GSK-3β時，將促進GSK-3β對GCM1上Ser322位置的胺基酸進行磷酸化，促使GCM1與F-box protein FBW2結合，提高被汎素化的程度，而經由26S proteasome進行降解。 於此篇研究中進一步發現，除了對GCM1進行磷酸化作用，細胞中亦存在一特殊的dual-specificity protein phosphatases磷酸水解酶—GIP1，可藉由與GCM1的交互作用，對GCM1進行去磷酸化反應，以逆向調控Ser322位置的磷酸化程度，藉此而降低GCM1被汎素標定的現象，延緩於細胞中被降解的速率，而相對提高其穩定性和轉錄活性。因此，於胎盤發育的過程中，藉由GSK-3β與GIP1對GCM1磷酸化程度的交互調控，將可維持細胞中GCM1一定的穩定度和表現量，以適時促進融合滋養層的分化與發育，維持胎盤功能及構造上的完整。Human GCM1 (Glial cell missing homolog 1) is a placenta-specific transcription factor, which regulates expression of syncytin, a fusogenic membrane protein, and controls the formation of syncytiotrophoblast layer essential for nutrient and gas exchange. In previous studies, we have demonstrated that GCM1 activity can be regulated by different post-translational modifications, including phosphoryaltion, ubiquitination, sumoylation and acetylation. Very recently, it has further been demonstrated that activation of GSK-3β by hypoxia leads to GCM1 phosphorylation on Ser322, which in turn recruits the F-box protein FBW2 to trigger GCM1 ubiquitination and degradation. In this report, we further identify a dual-specificity protein phosphatase termed GIP1 (GCM1-interacting protein 1), which regulates GCM1 dephosphorylation on Ser322 leading to reduction in GCM1 ubiquitination, and therefore increase in GCM1 stability and transcriptional activity. Together with our previous findings, GCM1 protein stability is reciprocally regulated by GSK-3β and GIP1, which may be critical for regulation of trophoblastic fusion and differentiation of syncytiotrophoblast layer.目 錄 ……………………………………………………………………I文摘要………………………………………………………………III文摘要 ………………………………………………………………IV一章 緒論.1 胎盤…………………………………………………………………1.2 人類內生性反轉錄病毒……………………………………………2.3 gcm 轉錄因子………………………………………………………4.4 磷酸水解酶…………………………………………………………6.5 研究動機……………………………………………………………9二章 材料及方法.1 重組質體的構築……………………………………………………10.2 重組蛋白在人類細胞的表現………………………………………14.3 共同免疫沉澱法……………………………………………………18.4 Luciferase螢光報告基因活性檢測………………………………18.5 活體內汎素化作用分析……………………………………………19.6 Cycloheximide-chase assay ……………………………………19.7 活體外交互作用分析………………………………………………19.8 活體外磷酸化及去磷酸化分析……………………………………21三章 實驗結果.1 GIP1和GCM1轉錄因子的交互作用…………………………………23.2 GIP1對GCM1蛋白穩定度的影響……………………………………24.3 GIP1對細胞內GCM1汎素化的影響…………………………………25.4 GIP1對細胞內GCM1降解速率的影響………………………………26.5 GCM1和GIP1進行交互作用的片段…………………………………26.6 活體外GIP1對GCM1的去磷酸化作用………………………………27.7 GIP1對細胞內GCM1的去磷酸化作用………………………………28.8 GIP1對GCM1生理作用的分析………………………………………29四章 討論與總結 ……………………………………………………30五章 圖表 ……………………………………………………………33六章 參考文獻……………………………………………………… 4
Changes in architecture of muscle-tendon unit and performance of gastrocnemius using elastic taping
No full text肌肉的結構與肌腱和腱膜的物理特性會因為不同的訓練和運動而產生適應性的變化，進而提高運動表現。但這些改變肌肉結構或肌腱和腱膜特性的訓練或運動，都需要持續一定的時間，才會出現變化；目前尚無可立即改變肌肉結構變化的運動訓練方式。然而近年來運動選手們常利用彈性貼紮來促進運動表現，但彈性貼布本身是一種物理性的介入，且具有立即的效應，因此其效應或許來自改變了肌肉的物理特性。然而目前鮮有研究探討其對運動表現的影響，遑論探討彈性貼紮對於肌肉肌腱單位結構和物理特性影響的研究。因此，本研究在有無腓腸肌彈性貼紮的狀況下，進行單腳垂直跳測試，以檢視彈性貼紮對動作表現的影響。並在有無腓腸肌彈性貼紮的狀況下，進行單腳蹲踮測試，量測腓腸肌內側頭之肌肉肌腱交點偏離度、肌束長度、淺層肌束角度、深層肌束角度、肌肉厚度等肌肉結構參數，以了解彈性貼紮是否可改變單腳蹲踮動作過程中的腓腸肌肌肉肌腱單位結構的變化。研究屬於便利抽樣、前瞻性、介入性、順序隨機和前後側的研究設計，共收取30名符合條件的健康成年人分別在有無貼紮的狀況下，進行單腳蹲踮和單腳垂直跳測試。在單腳蹲踮測試時，以超音波影像儀擷取腓腸肌內側頭中點和末端的影像，並同步以電子量角器記錄踝關節角度的變化。在超音波影像上量測腓腸肌內側頭的肌肉肌構單位結構參數，包括肌肉肌腱交點的偏離度、肌束長度、淺層肌束角度、深層肌束角度、肌肉厚度等。單腳垂直跳測試時，則以垂直跳測量板量測其跳躍時對側手能碰觸的最高高度，並以站立時的基礎高度作標準化。有無貼紮的次序依亂數表做隨機分組，以降低疲憊或學習效應的影響。以重複量測變異數分析比較單腳垂直跳高度在有無貼紮狀況下是否存在顯著差異；在控制踝關節角度下，以混合模型分析比較在單腳蹲踮時，腓腸肌內側頭肌束長度、淺層肌束角度、深層肌束角度、肌肉厚度和腓腸肌肌肉肌腱交點偏離度的改變在有無貼紮狀況的差異。所有統計分析的顯著水準訂在α=0.05。研究結果顯示，腓腸肌彈性貼紮與否不會明顯地改變單腳垂直跳高度，但因不同人的垂直跳高度在貼紮後的變化有極大不同，因此依貼紮後的單腳垂直跳高度改變情形，將受試者分為增高組（增高1cm以上者）與降低組（降低1cm以上者），作進一步的分析。對於腓腸肌肌肉肌腱交點的偏離度，彈性貼紮會減低由蹲下至踮起時，肌肉肌腱交點向近心端的偏離度；但其他的肌肉結構參數都沒有差異。若再進一步檢視增高組與降低組，則發現增高組的腓腸肌內側頭肌束長度在彈性貼紮時，會降低由蹲下至踮起時的最大縮短量，而降低組的則會明顯的增加，因此顯示彈性貼紮可能會改變腓腸肌肌肉肌腱單位結構的部分物理特性。研究由腓腸肌肌肉肌腱單位結構的觀點來檢視彈性貼紮的作用，發現藉由黏貼皮膚的彈性貼紮可以改變部分肌肉肌腱單位結構的物理特性，此結果可提供臨床應用上的實證參考。口試委員會審定書----------------------------------------------------------------ii謝----------------------------------------------------------------------------------iii文摘要---------------------------------------------------------------------------- v文摘要----------------------------------------------------------------------------vii錄---------------------------------------------------------------------------------- x目錄------------------------------------------------------------------------------xiii目錄------------------------------------------------------------------------------xiv一章、前言---------------------------------------------------------------------- 1一節、研究背景與動機------------------------------------------------- 1二節、研究目的---------------------------------------------------------- 3三節、研究問題與研究假說------------------------------------------- 4四節、名詞解釋---------------------------------------------------------- 5二章、文獻回顧---------------------------------------------------------------- 7一節、彈性貼紮---------------------------------------------------------- 7二節、肌肉肌腱單位的結構-------------------------------------------10三節、腓腸肌的肌肉肌腱單位結構與生物力學-------------------12四節、肌肉肌腱單位結構之相關研究方法學----------------------15五節、超音波影像在肌肉肌腱單位結構研究之應用-------------17三章、研究方法----------------------------------------------------------------20一節、研究設計----------------------------------------------------------20二節、受試者-------------------------------------------------------------21三節、實驗儀器與設備-------------------------------------------------22四節、實驗流程----------------------------------------------------------24五節、影像處理與量測-------------------------------------------------27六節、統計分析----------------------------------------------------------28四章、結果----------------------------------------------------------------------30一節、電子量角器的電壓與角度關係-------------------------------31二節、肌肉肌腱單位結構的再測信度-------------------------------31三節、受試者的基本資料----------------------------------------------32四節、彈性貼紮對單腳垂直跳高度的影響-------------------------33五節、彈性貼紮對腓腸肌肌肉肌腱交點偏離度的影響----------34六節、彈性貼紮在腓腸肌放鬆時對其肌肉結構參數的影響----36七節、彈性貼紮在單腳蹲踮測試時對其肌肉結構變化的影響--36五章、討論-----------------------------------------------------------------------38一節、彈性貼紮對動作表現的影響-----------------------------------38二節、彈性貼紮對腓腸肌肌肉肌腱單位結構的影響--------------39三節、本研究的優點與貢獻--------------------------------------------40四節、本研究的限制----------------------------------------------------41六章、結論----------------------------------------------------------------------43-------------------------------------------------------------------------------------44-------------------------------------------------------------------------------------51考文獻----------------------------------------------------------------------------69錄一-------------------------------------------------------------------------------81錄二-------------------------------------------------------------------------------8
Structure-Based Lead Optimization with Synthetic Accessibility in Computer-Aided Drug Design
No full text先導藥物結構最適化是藥物開發中重要的一環，然而在抑制劑設計上，化學合成可行性亦是設計的一項考量。因此為設計出結構適化的抑制劑，並考慮合成可行性，本研究將針對先導藥物結構最適化的設計方法探討，根據其設計的演算法分為兩種，一為跳躍示式分子子結構置換，另一為考慮合成可行性的藥物設計。
在論文第一部分，將詳述LeadOp系統，此系統以蛋白質結構為基礎，針對已知的抑制劑結構，利用跳躍示式分子子結構置換方法結構優化已知的抑制劑結構，進而找出更有效的抑制劑。LeadOp考慮已知抑制劑分子的子結構，藉由計算Group efficiency (GE)的計分，評估子結構與蛋白質活性區的作用關係，並從資料庫中選出子結構較佳者進行替代；同時，我們考慮到分子性質並作為篩選條件，排除不穩定的子結構，並選出具有增加分子之間作用性質的子結構做置換。置換完的分子經過結構最佳化以及分子與蛋白質結合能量的計算，篩選出較佳的分子作為抑制劑。在此論文第二部分中，將詳述LeadOp+R 系統, 此系統同時評估抑制劑分子與蛋白質活性區的作用關係以及先導藥物設計上之分子可合成性，進而達到先導藥物結構最適化的設計。從預先擷取的化學反應合成上的規則，並以蛋白質結構為基礎，根據化學反應規則進行蛋白質活性區塊中之抑制劑分子合成，同時每一化學反應步驟的產物皆以GE排序計分，分數較高者將被視為新的反應物進行下一步合成直到系統執行結束，最後合成的產物將是結構最適化後的分子。
本論文中，分別以三組藥物及相對之蛋白質系統，依序BRaf、5-LOX、Tie-2，進行演算法上結構最適化的評估以驗證LeadOp、LeadOp+R的效能，進而設計出已知的藥物，其抑制活性與預測的結果有相同的趨勢。In this thesis, we describe two systems of structure based de novo optimization process, called “LeadOp” (short for Lead Optimization), and “LeadOp+R” (short for Lead Optimization with chemical Reaction).
In the first system, LeadOp, we described a structure based de novo optimization process, “LeadOp”, by decomposing a structure into fragments of different parts either by chemical rules or user-defined, evaluate each fragment at each part in a pre-docked fragment database that ranked fragments according to specific fragment-receptor binding interactions, replace fragments with less contribution to binding, and finally reassemble fragments from each part to form a ligand. The fundamental idea was to replace “bad” fragments of an inhibitor and replace with “good” fragments while leaving the rest of the inhibitor in the original core to improve the activity for lead optimization. The fragments were selected from a collection of 27,417 conformers by exhaustive docking at the target binding sites from synthesizable docked molecular building blocks and fragments from decomposing all known inhibitors from DrugBank database and related inhibitors. However, even with the fragment based design from common building blocks, it is still a challenge for synthesis. In the second system, “LeadOp+R” was developed based on 198 classical chemical reactions to consider the synthetic accessibility while optimizing leads. LeadOp+R first allows user to identify a preserved space defined by the volume occupied by a fragment of the query molecule to be preserved. Then LeadOp+R searches for building blocks with the same preserved space as initial reactants and grows molecules towards the preferred receptor-ligand interactions according to reaction rules from reaction database in LeadOp+R. Multiple conformers of each intermediate product were considered and evaluated at each step. The conformer with the best group efficiency score would be selected as the initial conformer of the next building block until the program finished optimization for all selected receptor-ligand interactions.
The two systems were examed with three biomolecular sysmtes, including mutant B-Raf kinase, Tie-2 kinase, and human 5-LOX inhibitor design. The “LeadOp” methodology was able to optimize the query molecules and systematically developed improved analogs for each of our example systems. The “LeadOp+R” methodology optimized the query molecule and systematically developed improved analogs along with their proposed synthetic routes. The suggested synthetic route (proposed from our synthesis algorithm) was the same as the published synthetic route devised by a synthetic/organic chemist
A Study on the Geographic Information Exam Questions of the College Entrance Examination
No full text自民國88年開始實施的高中地理新課程，高三上學期選修地理的課程有60％ 的內容與地理資訊有關，而95年新課程更將地理資訊納入高一課程。面臨資訊時代來臨及國際競爭，高中學生的地理資訊技能是未來公民的基本素養，然而相關研究尚不普遍。地理資訊在課程上的重視也反映在入學考試上，近幾年來，地理資訊試題陸續見於入學考試的地理科上。現行大學多元入學考試測驗目標在於檢測考生應具備的學科知識，以及對於資料的閱讀、判斷等能力，推理、分析等思考能力，表達能力及學科知識的應用能力。而地理資訊試題是否能適切地反應教學目標和教材內容， 達到真正檢驗學生是否具備「地理資訊」的能力？本研究以近年大學入學考試中心的測驗結果為素材，探討地理資訊受重視的情形、學生的認知成就、試題的適切性以及教學可提升之處。本研究從相關大學入學考試中挑選出地理資訊相關試題，針對題目內涵及作答情形進行統計分析，探討地理資訊類試題之比重、通過率、鑑別度與概念的配置情況。研究結果顯示地理資訊試題的通過率與鑑別度均略高於整體試題平均，然無顯著差異。透過個別試題的選項分析，本研究進一步找出教學難點、迷思概念，並提出高中地理資訊教學之相關建議。Facing the information era and increasing international
competitions, the proficiency of geographic information of senior high school students is a fundamental quality of future citizens. Yet, such issues have not attracted much research interest. This research uses the test result of College Entrance Examination as material to explore the ratios, accomplishment of students, and adequacy of questions related geographic information subjects. We first
identified and selected questions related to geographical information from the questions sheets. The difficulty, discrimination, and distribution of items of these selected questions were further analyzed. The results of such analysis indicate that the difficulty and discrimination of the questions are slightly higher than the average while not significant statistically. Based on analysis of individual questions, we further identified the difficult concept and myths of geographic information subject and made suggestions to high schools geography education.第一章 緒論...............................................1
第一節 研究背景與動機.................................. 1
第二節 研究目的........................................ 3
第三節 研究範圍與限制.................................. 4
第二章 文獻回顧.......................................... 5
第一節 大學入學考試.................................... 5
第二節 地理資訊與高中地理教育......................... 16
第三節 試題分析與命題原則............................. 26
第四節 布魯姆認知分類................................. 37
第三章 研究方法......................................... 44
第一節 研究對象與問題................................. 44
第二節 研究方法....................................... 44
第三節 研究步驟....................................... 45
第四節 研究架構與流程................................. 45
第四章 研究成果......................................... 47
第一節 地理資訊試題的比重與分配....................... 47
第二節 難易度與鑑別度分析............................. 50
第三節 選項分析....................................... 54
第四節 試題知識類型與認知歷程分布情形................. 56
第五節 地理資訊試題各概念比較......................... 58
第六節 個別試題分析................................... 60
第五章 結論與建議....................................... 82
第一節 結論........................................... 82
第二節 建議........................................... 83
參考文獻................................................ 85
附 錄................................................... 9
Study on the Mechanisms of Modulatory Effects of Mesenchymal Stem Cells on Airway Inflammation in Murine Model of Asthma
No full text氣喘是兒童常見的過敏性疾病之一，在過去幾年來其發生率有逐年增加的趨勢。目前已知過敏性氣喘是由第二型T輔助細胞所引起，通常伴隨有呼吸道過度反應和嗜酸性白血球浸潤，黏液分泌過多，甚至是呼吸道重塑等症狀。間葉幹細胞 (mesenchymal stem cells, MSCs) 來自於骨髓中，屬於多潛能性幹細胞 (multipotent stem cells)，是一種具有自我更新、繁殖並能分化成不同種類的組織和任一型態的細胞。近年來，有許多研究報告顯示間葉幹細胞具有免疫調節的功能。本篇研究希望透過小鼠尾巴靜脈注射方式打入間葉幹細胞，藉此降低由卵清蛋白 (ovalbumin, OVA)所誘發的發炎現象。首先，我們利用老鼠骨髓細胞培養出間葉幹細胞，並在適當的刺激下，體外培養分化成骨細胞 (osteocytes)和脂肪細胞 (adipocytes)，同時確認間葉幹細胞的表面標誌。此外，我們在試管內測試間葉幹細胞其免疫抑制的功能，發現在免疫細胞刺激劑 (Concanavalin A, ConA）刺激下，或是在混和淋巴細胞反應 (mixed lymphocyte reaction, MLR)中，當脾臟淋巴細胞與間葉幹細胞共同培養時，間葉幹細胞都能有效抑制脾臟淋巴細胞的增生。更進一步地，我們利用OVA致敏BALB/c小鼠，並以尾巴靜脈注射方式打入間葉幹細胞，再給予鼻腔刺激OVA引發呼吸道發炎，藉以研究其治療效果。結果顯示，給予間葉幹細胞可有效緩和呼吸道過度反應，減輕肺部沖洗液中嗜酸性白血球的發炎反應，以及降低血清中OVA特異性的IgE含量。此外，在給予間葉幹細胞的小鼠其脾臟淋巴細胞經OVA刺激下，不僅能抑制脾臟淋巴細胞的增生，同時可產生大量的介白素-10 (interleukin-10, IL-10)和干擾素-γ (interferon-γ, IFN-γ)。因此，我們認為給予間葉幹細胞能減緩過敏性氣喘的傾向，未來將會更進一步研究間葉幹細胞在免疫抑制上的作用機制。Asthma is one of the most common allergic diseases in children and its prevalence has been increased in recent decades. Allergic asthma is characterized by the induction of T helper 2 cells, airway hyperresponsiveness, eosinophil infiltration, increased mucus secretion and even airway remodeling. Mesenchymal stem cells (MSCs) are a self-renewing population of multipotent stem cells present in bone marrow and can differentiate into a variety of tissues or cell lineages. Recent studies have demonstrated that MSCs could exert an immunosuppressive function. This study was performed to investigate whether MSCs could inhibit OVA-induced allergic airway inflammation in murine model. First, MSCs were isolated from mouse bone marrow, characterized by their phenotypes, and differentiated into osteocytes and adipocytes in the appropriate induction media. In addition, the immunosuppressive function of MSCs was determined in vitro. The results indicated that MSCs exerted effectively inhibitory effect on the proliferation of lymphocytes under ConA stimulation or the mixed lymphocyte reaction. Furthermore, to investigate the effect of MSCs on the allergic asthma, the female BALB/c mice were sensitized with ovalbumin (OVA) by intraperitoneal injection, 1×106 MSCs were injected intravenously before each OVA challenge. In the study, we found that the airway hyperresponsiveness, eosinophilic inflammation in bronchoalveolar lavage fluid, and OVA-sprcific IgE in serum were diminished after MSCs administration. Additionally, MSCs delivered in mice not only inhibited the proliferation of OVA-specific lymphocytes but also increased the levels of IL-10 and IFN-γ. Therefore, we demonstrated that administration of MSCs could alleviate airway inflammation in OVA-induced murine model of asthma. In the future, it will be interesting to clarify the immunomodulatory mechanisms of MSCs
Polymersomes with high loading capacity prepared by solvent annealing method and their controlled release behaviors
No full text雙親性團聯式共聚物可以於選擇性溶劑形成自組裝結構，其中喜好溶劑的鏈段傾向和溶劑接觸，而不喜好溶劑的鏈段被屏蔽遠離溶劑，不同於傳統製備液胞方法，我們發現團聯式共聚物PS-b-PAA、PS-b-PEO和PCL-b-PEO可以藉由溶劑退火的方式在藥物分子阿斯匹靈中自組裝形成液胞，當添加團聯式共聚物於大量阿斯匹靈中，阿斯匹靈會與共聚物的其中一嵌段結合，猶如選擇性溶劑膨潤該嵌段，使體積分率改變，形成雙層結構，於溶劑退火的過程中，滲入的溶劑賦予團聯式共聚物和阿斯匹靈移動力，使雙層結構能夠環起來形成內外皆充滿阿斯匹靈的液胞。此溶劑退火的方式，可以避免傳統高溫熱退火製備液胞時，造成藥物分子發生不必要的化學反應，當我們以穿透式電子顯微鏡觀察經由適當溶劑所萃取的液胞結構，發現該液胞結構具有充滿藥物的核心，藥物承載的能力高達59±5％，遠高於溶液系統中所形成的傳統液胞結構藥物承載能力約30-40%。我們也測試了包覆阿斯匹靈液胞的釋放行為，發現PS-b-PAA液胞可經由控制將阿斯匹靈釋放出來，在水溶液中加入不同比例的dioxane，因dioxane可膨潤PS和PAA鏈段，能增加液胞穿透度，促使阿斯匹靈釋放，此外，我們也觀察液胞在不同pH值溶液下的釋放行為，發現藥物的累積釋放量明顯受pH值影響。It is well known that amphiphilic block copolymers in selective solvents can form self-assembled structures, where solvophilic blocks tend to contact with solvents while solvophobic blocks are shielded from the solvents. Different from the conventional preparation of vesicles in liquid systems, we found that block copolymers, including poly(styrene-b-acrylic acid) (PS-b-PAA), poly(styrene-b-ethylene oxide) (PS-b-PEO), and poly(caprolactone-b-ethylene oxide) (PCL-b-PEO), can directly self-assemble into vesicles in aspirin, a drug molecule, by solvent annealing. When mixing the block copolymers in a great amount of aspirin, aspirin works as “selective solvent” that associates with one of the blocks and swells the block, thus changing the volume fraction of the blocks, which firstly leads to the formation of bilayer structures. During following solvent annealing, the penetrated solvent molecules impart mobility to block copolymers and aspirin. The bilayers are then wrapped into vesicles with aspirin filled in both interior and exterior. The advantage of solvent annealing method is that it prevents unnecessary chemical reactions of drug molecules that may be caused by conventional thermal annealing method at high temperature. The vesicular structures after extracting by appropriate solvents were probed by transmission electron microscopy (TEM). The extracted vesicles are filled with aspirin in the core and the drug loading content can reach as high as 59±5％, which is much higher than that of conventional vesicles formed in liquid systems (~30-40%). We have tested the release behaviors of the aspirin-loaded vesicles. Aspirin can be released in a controlled manner from PS-b-PAA vesicles in aqueous solutions with different concentrations of n-dioxane, a good solvent to both PS and PAA blocks. We also examined the effect of pH values on the release behaviors of the aspirin-loaded vesicles in aqueous solutions. The cumulative release of aspirin was found to be strongly pH-dependent.誌謝 I
Abstract II
摘要 IV
Table of contents V
List of figure VII
Chapter 1 Introduction 1
1-1 Background 1
1-2 Motivation and Objectives 3
Chapter 2 Theory and Literature Review 5
2-1 Block copolymer and supramolecules 5
2-1.1 Block copolymer 5
2-1.2 Supramolecules 10
2-2 Amphiphilic block copolymers micellar solution 17
2-3 Blend of diblock copolymer 24
2-3.1 Block copolymer self-assembled in homopolymer 24
2-3.2 Block copolymer self-assembled in small molecule 27
2-4 Polymersomes for drug release 30
Chapter 3 Experimental Section 34
3-1 Materials 34
3-2 Experimental methods 38
3-2.1 Preparation of bulks 38
3-2.2 Annealing procedure 38
3-2.3 Ultrathin session 38
3-2.4 Extraction of self-assembled structures 39
3-2.5 Drug release 39
3-3 Characterization 42
Chapter 4 Results and Discussion 44
4-1 The interaction between PS-b-PAA and aspirin 44
4-2 Preparing vesicles from amphiphilic block copolymers by solvent annealing 52
4-2.1 Aspirin-loaded vesicles of PS(42000)-b-PAA(4500) 52
4-2.2 Aspirin-loaded vesicles formed by PS-b-PAA with different molecular weight 62
4-2.3 Aspirin-loaded vesicles formed from other block copolymers 68
4-3 Release of aspirin from polymersomes 72
4-3.1 Aspirin released from vesicles in n-dioxane/water mixtures 73
4-3.2 Aspirin released at different pH values 77
Chapter 5 Conclusions 83
Reference 8
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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