http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94 Thu, 12 Mar 2026 10:14:26 GMT 2026-03-12T10:14:26Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26451 標題: 鼻腔噴霧器體外生體相等性統計評估：小霧滴大小分佈; Statistical Evaluation of In Vitro Bioequivalence for Nasal Aerosols and Nasal Sprays for Local Action：Droplet size Distribution 作者: Chung-hsien Yue; 游忠憲 摘要: 為了學名與原廠鼻腔噴霧器之生體相等性，本論文藉由與標準鼻腔噴霧器的噴霧效果來做比較是否為生體相等。在試驗過程中，因噴霧藥效為局部性的，並不會進入血液而影響其他身體器官，未避免人體實驗中包含的變異(如：力道、吸氣量…等)，所以以機器實驗來取代人體實驗。在分析過程中，我們關注的有噴霧樣本、小霧滴大小分佈及雲霧狀幾何學，而分析方法是採用非剖析分析(nonprofile analyses)。最後的判定準則是將我們的標準線性化後，去觀測其95%信賴區間的上界，依結果判定學名噴霧器是否與原廠噴霧器為生體相等性。; In order to evaluate bioequivalence between the generic and innovator investigate the equivalence in characteristics between the generic and innovator nasal aerosols. Because the nasal aerosols only act locally and its active ingredient does not absorb into the body system, therefore in vivo bioequivalence studies are replaced by the in vitro bioequivalence studies using machinery experiment to avoid variability caused the factors much that volume of breath. The quality of nasal aerosols and sprays can be characterized by spray patterns, droplet size distribution and plume geometry. The 2003 US FDA draft guidance proposed the application of population bioequivalence to evaluate the in vitro bioequivalence between the generic and innovator nasal aerosols and sprays. Such analysis is referred to as the nonprofile analysis. We applied the statistical methods of in vitro bioequivalence in the US FDA guidance to a dataset of droplet size distribution. We also compare and discuss the results obtained under the 2-stage nested random-effects model and the model suggested in the 2003 US FDA draft guidance. Tue, 01 Jan 2008 00:00:00 GMT http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26451 2008-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74515 標題: 黑豆油高光譜分析與色素含量之研究; Study on Hyperspectral Analysis and Pigment Content of Black Soybean Oil 作者: Zhi-Jia Wu; 吳致嘉 摘要: 黑豆 (Glycine max L.) 富含蛋白質、碳水化合物和脂肪類，並含有礦物質、維生素、葉酸、花青素 (anthocyanin)、異黃酮、類黃酮、卵磷脂、酚酸等營養物質，為人們飲食中良好的營養成份來源。黑豆之初級壓榨黑豆油富含花青素、類胡蘿蔔素 (carotenoid) 和葉綠素 (chlorophyll) 等色素，這些色素對人體具有保健功效。目前黑豆油色素之相關研究極少，因此本研究擬透過利用高光譜吸收值與色素指數來建立簡單、快速並準確地測定黑豆油色素含量之預測模式。試驗材料之黑豆油以黑豆「台南3號」為原料，進行3種種皮添加和2種儲藏期間處理。測定黑豆油之高光譜吸收值以及花青素、類胡蘿蔔素、葉綠素a、葉黃素 (lutein)、玉米黃素 (zeaxanthin) 和葉綠素b含量。高光譜吸收值和色素指數與黑豆油中個別色素含量進行相關分析，並建立黑豆油色素預測模式。進一步將蒐集的9種黑豆油驗證樣品之高光譜吸收值和色素指數代入個別預測模式中，獲得各色素含量之預測值與實測值以殘差分析進行驗證。黑豆油花青素含量之最佳預測模式為高光譜吸收值A530和A649，差異色素指數DPI535, 524、DPI650, 575、DPI650, 588和DPI600, 710之預測模式。黑豆油類胡蘿蔔素含量之最佳預測模式為高光譜吸收值A440，差異色素指數DPI441, 524、DPI441, 575、DPI441, 588、DPI440, 710和DPI578, 710之預測模式。黑豆油葉綠素a含量之最佳預測模式為高光譜吸收值A450和A667，差異色素指數DPI668, 524、DPI430, 575、DPI667, 575和DPI667, 588之預測模式。葉黃素相對含量之最佳預測模式為高光譜吸收值A522和A547之預測模式。玉米黃素相對含量之最佳預測模式為高光譜吸收值A727之預測模式。葉綠素b相對含量之最佳預測模式為高光譜吸收值A641，差異色素指數DPI640, 575、DPI641, 588和DPI640, 710，比率色素指數RPI590, 575和RPI641, 710之預測模式; Black soybeans (Glycine max L.) are rich in protein, carbohydrates and fats, including minerals, vitamins, folic acid, anthocyanins, isoflavones, flavonoids, lecithin, phenolic acid, making them a good source of nutrients in daily diet. The first pressed black soybean oil is rich in pigments such as anthocyanins, carotenoids and chlorophyll, which have beneficial effects on human health. At present, there are only a few studies on black soybean oil pigment. Therefore, this research aims to establish a simple, rapid and accurate prediction model for the determination of black soybean oil pigment content by using hyperspectral absorbance and pigment index. The tested black soybean oil was obtained from black soybean ‘TN3’, with three seed coat additions and two storage periods. The hyperspectral absorbance of black soybean oil and the content of anthocyanin, carotenoid, chlorophyll a, lutein, zeaxanthin and chlorophyll b were measured. In order to establish the prediction model for the pigments, the hyperspectral absorbance and the pigment index were compared with the content of the individual pigments simultaneously and the correlations between them were found. The data collected from nine different black soybean oils were further applied into the prediction model. The verification of the prediction model was done by performing residual analysis, comparing the predicted and the measured content of each pigment. The optimal prediction model for anthocyanin is achieved by using the hyperspectral absorbance A530 and A649 and differential pigment index DPI535, 524, DPI650, 575, DPI650, 588 and DPI600, 710. As for the carotenoid, best prediction results were gained with the hyperspectral absorbance A440 and the differential pigment index DPI441, 524, DPI441, 575, DPI441, 588, DPI440, 710 and DPI578, 710. On the other hand, the best prediction of chlorophyll a were the ones with the hyperspectral absorbance A450 and A667 and the differential pigment index DPI668, 524, DPI430, 575, DPI667, 575 and DPI667, 588. As for the relative content of lutein, the optimal prediction outcome was obtained with hyperspectral absorbance A522 and A547. As for the relative content of zeaxanthin, the optimal prediction outcome was obtained with hyperspectral absorbance A727.The best prediction model for the relative content of chlorophyll b is with hyperspectral absorbance A641, differential pigment index DPI640, 575, DPI641, 588 and DPI640, 710, ratio pigment index RPI590, 575 and RPI641, 710. Fri, 01 Jan 2021 00:00:00 GMT http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74515 2021-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50850 標題: 高維度平均值對等性檢定之研究; A Study on High-dimensional Equivalence Test of Means 作者: Chen-Hao Chiu; 邱振豪 摘要: 傳統上若要進行多變數的兩樣本檢定，研究者多會使用Hotelling’s T2檢定，但由於高維度資料的其中一項特性是通常變數數目 (維度)遠大於樣本數，這會使得Hotelling’s T2檢定在高維度下因為無法計算出統計檢定量所需的樣本共變異矩陣之反矩陣而無法使用，同時也讓統計學者在相關推論上比較困難。前人們陸陸續續提出過許多改善方法，例如Cai, et al. (2014)提出在變異數矩陣同質假設及高維度下檢定兩平均向量是否相等的方法，並證明檢定統計量在變數個數趨近於無窮大時其近似分布為第一型極值分布 (Type I extreme-value distribution)。 對等性 (equivalence)評估之目的在評估兩族群指標平均向量差異是否落於研究者所訂定的對等範圍內 (equivalence limits)，然而在如生物相似性產品 (biosimilar product)、基改產品 (GMO)等領域上若執行對等性評估，有可能會遇到評估的變數很多但觀測值相對很少的情況，但目前尚無高維度的對等性評估統計檢定方法。有鑑於此，我們在研究中將會提出兩種方法，第一種為根據交集-聯集原則所建立，在每個變數上都執行t對等性檢定的方法；第二種則為應用Cai, et al. (2014)的研究，命名其為最大Z2的高維度對等性檢定，其中包含了兩種程序，分別為在兩族群共變異矩陣是否已知的情況下作推導其形式與結果會有些許不同。 在這份研究中我們展示大規模的模擬研究成果，並提供實際的高維度資料範例證明提出方法之應用。根據模擬研究成果顯示，對於第一種的交集-聯集方法，由於其要求每個變數都要能宣稱對等性成立，以至於太過於保守而近乎無法拒絕虛無假說來宣稱整體的對等性。而另一方面，第二種的最大Z2對等性檢定則由於只看最大值，因此不會如前種方法嚴謹，且在模擬的型一錯誤率部分，兩個程序都能夠控制在我們所要求的顯著水準附近，同時在模擬的檢定力部分，兩個程序也都能夠提供足夠大的檢定力，證明最大Z2對等性檢定除了能夠控制型一錯誤率外，也能夠在真實的對等性情況去作偵測。; Hotelling’s T2 test is a canonical multivariate two-sample test. However, due to the property of high-dimensional data that the number of variables is typically greater than the sample size, the inverse of the sample covariance matrix required by the test is not obtainable. Hotelling’s T2 test hence becomes inapplicable to high-dimensional data. Such property has become a conundrum for researchers to solve, and a few researchers have proposed improved methods accordingly. For example, Cai, et al. (2014) proposed a high-dimensional test of means under the assumption of common covariance matrix, and proved the asymptotic distribution of the test statistic, as the number of the variables becomes infinity, converges to a Type I extreme-value distribution. Equivalence testing is used for evaluating whether the mean difference between two populations falls within the equivalence limits specified by researchers. When using equivalence testing on the evaluation of biosimilar products, GMOs, etc., it is possible that the number of variables is large and the sample size is relatively small. However, previous studies on high-dimensional equivalence test of means are scarce. In the studies, we propose two equivalence tests of means. The first method is based on the intersection-union approach and executes individual equivalence t-test for every variable. The second method, maximal Z2 test, is derived from the study by Cai, et al. (2014) and is based on the maximal equivalence between the variables. The maximal Z2 test includes two different procedures, applying to the situations whether the common covariance matrix is known or not. The steps and test statistics of the two procedures are slightly different as well. We display the results of our simulation studies and also provide the demonstration of our methods on real high dimensional examples. According to our simulation studies, it suggests the intersection-union method is too conservative to reject the null hypothesis of overall equivalence because it requires every variable equivalent. On the other hand, the maximal Z2 method is expected to more liberal because it only tests on the maximal variable. Both procedures from maximal Z2 method can adequately control the empirical size at the significance level and they also both provide sufficient empirical power. The simulation studies indicate that the maximal Z2 test is a viable approach that can not only controls Type I error rate but also detects the true equivalent situation correctly. Fri, 01 Jan 2016 00:00:00 GMT http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50850 2016-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51344 標題: 高粱株高之基因定位; Mapping QTL Affecting Plant Height of Sorghum 作者: Yu-Hung Hsiao; 蕭宇宏 摘要: 高粱[Sorghum bicolor (L.) Moench] 為世界上第五大榖類作物，其用途非常廣泛。而不同用途之高粱有不同的株高偏好，生產生質酒精的高粱需要較高大的植株，而收穫種子的高梁則偏好半矮株。目前在臺灣高粱之主要用途為釀酒用，種植期間若遭遇颱風過高的植株會倒伏，故研究影響株高的QTL非常重要。本研究利用兩個糯性高粱品系F7X與E28A6雜交所產生的F_2族群進行株高基因的定位，並且利用混合分離族群分析法(BSA)、單一標誌分析法以及區間定位法進行階段式的基因定位，先找出與株高相關之分子標誌，再集中於與性狀相關之分子標誌週圍區域進行基因定位。研究結果發現在第二、六(2個)與七條染色體中共有4個與株高相關之QTL，包括sbHT2-2(第二條染色體)能解釋8.59%的變異，sbHT6a-59及sbHT6b-23(第六條染色體)則分別可解釋8.10%及16.97%的變異，及sbHT7-51(第七條染色體)則可影響10.19%的株高變異，而sbHT6b-23與sbHT7-51之間還存在交感效應，能影響5.75%的株高變異，此4個QTL組成的線性模式共能解釋約41%的株高變異。本研究定位出的QTL均能對應到前人研究中株高或株高相關性狀之候選基因，例如〖Dw〗_3、hda、Floricaula/leafy-like 2等基因。本研究推薦以TXP176、TXP295、TXP298及SB3479等4個分子標誌輔助株高之選拔，在4個分子標誌中，帶有兩對或三對矮化基因型植株較適合台灣環境的株高，而帶有兩對或三對顯性基因型植株則擁有中等株高，則亦適合作為雜交父本。且F_2族群中有2植株在4個分子標誌中帶有兩對矮化基因型，1株在三個分子標誌都為矮性基因型，有6株三個分子標誌均為顯性基因型，而有1株在4個分子標誌均為同型結合顯性基因型，上述9植株中有4植株在4個分子標誌均已為同型結合，可評估其他性狀做後續之利用。本研究的結果能應用在高粱育種計畫之中，可加速選育具有合適株高之優良高粱品種。; Sorghum [Sorghum bicolor (L.) Moench] is the fifth most important crop in the world. It has various utilizations. There are different preferences correlated with plant height for different uses. For example, the taller plants of sorghum are suitable for bio-energy. On the contrary, the semi-dwarf sorghum for seed production is recommended. In Taiwan currently, the main use of sorghum is brewing wine. To avoid the damage from typhoon, studies on QTLs affecting plant height are very important. In the study, a F_2 population crossed from two waxy sorghum inbred lines, (F7X and E28A6), was used. Bulk Segregant Analysis (BSA) was applied to find out the molecular markers linked with QTL affecting plant height, and interval mapping to locate the QTLs on the chromosomes. Four plant-height QTLs on chromosomes 2, 6, and 7 were mapped. The most significant QTL sbHT6b-23 is on the chromosome 6 and can it explain 16.97% variation of plant height. The other mapped QTLs were sbHT2-2 (chromosome 2), sbHT6a-59 (chromosome 6) and sbHT7-51 (chromosome 7), respectively explaining 8.59%, 8.10% and 10.19% of variation. We also observed interaction between sbHT6b-23 and sbHT7-51. The interaction could explain 5.75% of variation. These four QTLs and interaction would totally explain 41% of plant height variation. All mapped QTL are corresponding to genes in previous studies, like 〖Dw〗_3, had, and Floricaula/leafy-like 2. For marker-assisted selection, we recommend four SSR markers, TXP176, TXP295, TXP298 and SB3479. The plants carrying two or three homologous dwarf genotypes might be suitable for growth in Taiwan and those carrying two or three dominate homologous genotypes are idea to be the male parent for F1 hybrid production. In the F_2 population, there are two plants carrying two dwarf genotypes, one plants with three dwarf, six plants with three tall genotypes and one plant with four tall homologous genotypes. Notably, we found four plants with homologous genotypes for the four SSR markers closely linked with QTL affecting plant height. These four plants were selected for further evaluation. The results of the study could apply in sorghum breeding programs to select sorghum varieties with suitable plant height. Fri, 01 Jan 2016 00:00:00 GMT http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/51344 2016-01-01T00:00:00Z