1,721,015 research outputs found
Theoretical analysis and experimental measurement for resonant vibration of piezoceramic circular plates
No full textGeochemical Characteristics and Petrogenesis of Pre- to Post-collisional Igneous Rocks in Armenia and Caucasian regions
No full text阿拉伯與歐亞大陸板塊的碰撞造山，包含數個小地塊的拼貼或增積，因此被稱為土耳其式造山運動。此造山帶主要由高加索、伊朗以及安納托利亞高原所組成(簡稱為CIA地區)，碰撞前後均有廣泛分布的火成岩，前者為新特提斯洋向北隱沒所造成，後者約從11 Ma開始，形成機制多所爭議，本研究首先針對亞美尼亞境內的碰撞前與碰撞後火成岩進行地球化學與定年分析，討論岩石成因，再比對其他CIA地區碰撞後火成岩之地化性質與時空變化，綜合探討整個地區的碰撞後岩漿活動與地體構造演化。
本研究共分析採自亞美尼亞的12個碰撞前火成岩與35個碰撞後火成岩標本。結果顯示前者的形成年代介於57.5-26.5 Ma之間，屬中鉀鈣鹼性系列；後者的形成年代小於4.4 Ma，屬高鉀鈣鹼性系列。兩期火成岩皆具有輕稀土與其他高不相容元素的富集、高場力鍵結元素的虧損、並具有相似的鍶釹同位素組成(87Sr/86Sr ≈ 0.7040 to 0.7047; 143Nd/144Nd ≈ 0.5127 to 0.5129)。然而，碰撞後火成岩的鉀質與高不相容元素富集的程度明顯較高，根據稀土元素模擬計算，碰撞後火成岩之部份熔融程度(3-6%)較碰撞前火成岩(8-10 %)來得小，但兩者的地函源區均為尖晶石至石榴子石二輝橄欖岩過渡帶，約60-80公里深，且受過隱沒作用的富集，與其他CIA地區碰撞後火成岩之源區類似。
CIA地區的碰撞後岩漿活動不但普遍造成高鉀鈣鹼性系列岩石，還造成了埃達克岩與超鉀質岩。超鉀質岩目前只在伊朗西北部Saray火山被發現，噴發於11 Ma，具有相對富集的鍶釹同位素組成(87Sr/86Sr ≈ 0.7078; 143Nd/144Nd ≈ 0.5125)、由含金雲母之富集岩石圈地函發生小程度部份熔融而形成。埃達克岩分布較廣泛，約從6Ma肇始，由東安納托利亞經亞美尼亞到大高加索地區形成向東北逐漸年輕的噴發趨勢，並在伊朗西北部造成Sahand和Sabalan兩大火山，其鍶釹同位素組成均勻(87Sr/86Sr ≈ 0.7041 to 0.7050 and 143Nd/144Nd ≈ 0.5127 to 0.5128)，與其他碰撞後鈣鹼性火山岩無異、應屬碰撞增厚的基性底侵下地殼熔融所造成。
整個CIA地區之碰撞後鈣鹼性岩漿活動約始於11 Ma，有先向南再向東遷移的時空變化趨勢，推測是由於大陸碰撞起始地區東安納托利亞之下的新特提斯洋岩石圈先向南退卻(slab roll-back)、接著向東撕裂(tear migration, 約自6 Ma開始)、最後拆解(slab break-off, 約自2 Ma開始)的結果。此一地體構造改變，導致軟流圈上湧並造成岩漿活動的廣泛分布及時空變化。此外，CIA西南部的火山活動從2 Ma左右終止，推測是受到該地區岩石圈增厚的抑制，增厚的機制除了和碰撞相關的構造增厚之外，可能還包含新的岩石圈地函形成，後者為早期碰撞後岩漿活動在軟流圈頂部的熔融殘餘、具有耐熔的特性。因此，基於阿拉伯與歐亞兩大陸塊的異時斜向碰撞，碰撞後岩漿活動預期將會沿著札格洛斯縫合帶(Zagros suture)，向東南方向逐漸發展。Armenia is located in the Arabia-Eurasia continental collision zone that has also been considered as the product of the “Turkic-type” orogeny involving accretion of a number of terranes. Cenozoic magmatism in this zone, named CIA (Caucasus-Iran- Anatolia) province in this study, took place in two main stages that, respectively, pre- and post-date the Arabia-Eurasia collision. Whereas the pre-collisional magmatism has been generally ascribed to the Neotethyan subduction, how was the cause or mechanisam of the voluminous post-collisional volcanism formed has long been an issue of debates.
This study reports new ages and geochemical data of the pre- and post-collisional igneous rocks from Armenia. All the studied rocks are calc- alkaline and characterized by enrichment in LREE and other highly incompatible trace elements (e.g., Rb, Ba, Th, U), and depletions in the high field strength elements (e.g., Nb, Ta, Ti). These geochemical features, similar to those of coeval magmatic rocks from the CIA province, support the existence of a subduction- modified mantle that prevails throughout the Cenozoic. In Armenia, however, post-collisional rocks are more enriched in potassium and highly incompatible trace elements than pre-collisional ones. Post-collisional basalts [La=24-63 ppm; (La/Yb)N =5.8-20], for example, are more LREE-enriched than pre-collisional basalts [La=15-28 ppm; (La/Yb)N of 3.5-7.9]. All the Armenian rocks show rather uniform Sr-Nd isotopic ratios (87Sr/86Sr ≈ 0.7040 to 0.7047; 143Nd/144Nd ≈ 0.5127 to 0.5129), similar to the isotopic compositions reported in other CIA magmatic provinces. REE modeling suggests that Armenian pre- to post-collisional basaltic magmas were derived from a common mantle source that is located in spinel- to garnet-lherzolite transition region at ~60-80 km depth, with melting degrees being larger in the former (8-10 %) and smaller in the latter (3-6 %).
The Armenian results, combined with our data from other parts of the CIA province and literature information from E. Anatolia, allow us to better constrain the temporal, spatial and geochemical variations in the CIA province. The post-collisional volcanism began at ca. 11 Ma, and it shows change in time and space, prevailing during 9-6 Ma in E. Anatolia or the southwestern part of the CIA volcanic province and then migrating eastward. No volcanism occurred in the southwestern CIA province since ~2 Ma. Along with the predominant calc-alkaline rocks, adakites and ultrapotassic rocks are observed in the CIA volcanic province. The adakites are small-volume but widespread, erupting with a northeastward-younging trend from E. Anatolia to the Greater Caucasus. They have uniform Sr-Nd isotope ratios (87Sr/86Sr ≈ 0.7041 to 0.7050 and 143Nd/144Nd ≈ 0.5127 to 0.5128), similar to those of the other CIA post-collisional volcanics, suggesting a common mantle source. The ultrapotassic rocks that were emplaced in Saray, NW Iran, as one of the earliest eruptions (~11 Ma), have more “radiogenic” Sr-Nd isotope ratios (87Sr/86Sr ≈ 0.7078; 143Nd/144Nd ≈ 0.5125). The adakites are interpreted as partial melts of eclogitized lower crust, formed by basaltic underplating during the Neotethyan subduction and thickened by the collision, and the ultrapotassic rocks as small-degree melts of the metasomatized lithospheric mantle.
The driving force of the CIA post-collisional volcanism may be attributed to roll-back and then break-off of the subducted Neotethyan slab that, assuming an oblique/diachronous collision between Arabia and Eurasia, may have started from the northwest, i.e., beneath the southwestern CIA province, and propagated southeastward. Volcanism thus produced may later be ceased owing to the formation of new lithospheric mantle from below, as the melting residue, and subsequent crustal/lithospheric thickening caused by the continued collision. Under this framework, it is predictable that the post-collisional magmatism will eventually migrate southeastward along the Zagros suture zone
Algebraic Multigrid method of Kaczmarz method
No full textWe are concerned with the algebraic multigrid (AMG) method for least square problem arisen from image restorations. We employ the Kaczmarz’s method as the smoothers for the AMG and prove the corresponding smoothing property.Abstract vii
1 Introduction 1
2 CT and Radon transform 3
2.1 CT and Radon transform . . . . . . . . . . . . . . . . . . . . . 3
2.2 Discrete Radon transform . . . . . . . . . . . . . . . . . . . . 4
3 Kaczmarz’s Method and SOR method 7
3.1 Kaczmarz’s Method . . . . . . . . . . . . . . . . . . . . . . . . 7
3.2 SOR method . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.3 Kaczmarz method : a variant of SOR . . . . . . . . . . . . . . 10
3.4 Kaczmarz’s method for inverse Radon transform . . . . . . . . 12
4 Smoothing property of Kaczmarz’s method 15
4.1 Smoothing property of SOR method . . . . . . . . . . . . . . 16
4.2 Classical result . . . . . . . . . . . . . . . . . . . . . . . . . . 17
4.3 Consistent case . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4.4 Inconsistent case . . . . . . . . . . . . . . . . . . . . . . . . . 22
5 Algebraic Multigrid for general inconsistnet linear system 2
The anti-cancer mechanism of dasatinib against head and neck squamous cell carcinoma (HNSCC)
No full text本論文探討dasatinib引發頭頸癌細胞凋亡的藥理機轉。頭頸部鱗狀細胞癌(簡稱頭頸癌)是一個病程快速且預後不佳的世界性疾病。表皮生長因子受體(EGFR)會促進頭頸癌細胞的生長分裂，而其大量表現與頭頸癌的臨床預後不佳有關。雌激素受體(estrogen receptor)是一個作用廣泛的細胞核受體，能直接引發基因表現或是非基因表現的訊息傳遞。在頭頸癌中，雌激素受體會與表皮生長因子受體產生協同作用以促進細胞的生長與侵犯能力。近年來是標靶治療的時代，表皮生長因子受體的單株抗體cetuximab在頭頸癌成功的展現療效；儘管如此，cetuximab的效果仍然有限，頭頸癌整體治療成績仍然不佳，因此開發新的治療是重要課題。Dasatinib是一個對於Bcr-abl及Src均有抑制能力的磷酸激酶抑制劑(kinase inhibitor)，已被核准用於慢性骨髓性白血病的臨床治療，也被認為對於固態腫瘤具有治療潛力。然而在dasatinib於頭頸癌的臨床試驗中，雖然僅有少數病人得到效果，然而Src的抑制與療效之間並無關連，推測應有Src以外的機轉決定dasatinib的療效。本研究的第一部分指出，表皮生長因子的分解是一個決定dasatinib是否引發頭頸癌細胞凋亡的關鍵步驟，而此步驟是經由溶小體(lysosome)所完成。此外，雌激素受體也參與表皮生長因子受體調控dasatinib引發的細胞凋亡。進一步在動物模式中証實，dasatinib的確會藉由負調控(down-regulation)表皮生長因子及雌激素受體而抑制頭頸癌的生長。
本研究的第二部分則是進一步發現，dasatinib引發之表皮生長因子分解是來自於AMPK引發的內質網壓力(ER stress)。Dasatinib會引發內質網壓力，再經由c-cbl的作用促進表皮生長因子受體之分解。Dasatinib所誘發的AMPK活化可能是來自於PDK4增加導致細胞內之ATP下降。metformin引發AMPK活化則會增強dasatinib在細胞模式及動物模式中抑制頭頸癌的效果，在人類頭頸癌的檢體也發現AMPK活化與表皮生長因子受體表現的相關性。本研究指出dasatinib是經由AMPK-dependent ER stress導致表皮生長因子受體分解及頭頸癌細胞凋亡，藉由活化AMPK會進一步加強dasatinib對頭頸癌的療效，為頭頸癌的治療帶來進步。The mechanism of dasatinib-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells was investigated in this study. HNSCC is a worldwide disease with aggressive course and dismal outcome. The expression of epidermal growth factor receptor (EGFR) promotes cell growth and proliferation and is associated with clinical poor outcome of HNSCC. Estrogen receptor is a nuclear receptor which can exert both genomic and non-genomic actions. In HNSCC, estrogen receptor signaling is found to work in concert with EGFR to enhance cell growth and invasion. In the era of molecular targeted therapy, the emergence of cetuximab, an monoclonal antibody against EGFR, has led to a progress in HNSCC, but the efficacy is modest. Thus, new therapies are needed. Dasatinib is a Bcr-abl and Src inhibitor which has been approved for chronic myeloid leukemia and is expected to have activity against solid tumors. However, few patients benefit from dasatinib in clinical trials despite consistent Src inhibition, implicating that there are mechanisms beyond Src inhibition responsible for the efficacy of dasatinib. The first part of our study disclosed that EGFR degradation was the key event to mediate dasatinib-induced apoptosis in HNSCC cells. This event was through lysosome degradation. In addition, estrogen receptor was found to be associated with EGFR in dasatinib-induced apoptosis. Furthermore, xenograft model showed that dasatinib inhibited HNSCC tumor growth through in vivo down-regulation of EGFR and estrogen receptor.
In the second part of the study, we further investigated the mechanism of dasatinib-induced EGFR degradation and showed that AMPK-dependent endoplasmic reticulum (ER) stress is responsible for this event. Dasatinib induced ER stress which mediated EGFR degradation in a c-cbl-dependent manner. AMPK activation induced by dasatinib might be due to ATP decrease through the up-regulation of pyruvate dehydrogenase kinase 4 (PDK4). Furthermore, activation of AMPK by metformin sensitized dasatinib-induced in vitro and in vivo anti-cancer effect. The correlation of AMPK activation and EGFR expression was seen in HNSCC cells and human tumor specimens. Our results disclose that AMPK-dependent ER stress-mediated EGFR degradation plays a crucial role in the anti-cancer effect of dasatinib in HNSCC. Activation of AMPK by metformin might enhance dasatinib efficacy in HNSCC treatment.Abbreviation............................................2
中文摘要................................................4
Abstract in English.....................................5
Chapter I. Introduction
1. Head and neck squamous cell carcinoma (HNSCC)..6
2. Epidermal growth factor receptor (EGFR).......10
3. Src.......................................... 15
4. Estrogen receptor.............................19
5. BCL-2 family proteins and apoptosis...........22
6. Endoplasmic reticulum (ER) stress.............24
7. AMP-activated protein kinase (AMPK)...........26
8. Dasatinib and experimental rationale..........30
Chapter II. Materials and Methods......................31
Chapter III. Results
Part I. Degradation of epidermal growth factor receptor (EGFR) mediates dasatinib-induced apoptosis in head and neck squamous cell carcinoma cells.....................37
Part II. Metformin sensitizes anticancer effect of dasatinib in head and neck squamous cell carcinoma cells through AMPK-dependent ER stress.......................57
Chapter IV. Conclusion and perspective.................75
Reference..............................................78
Publications and Honors................................9
Preparation of mesoporous silica and carbon using gelatin or gelatin-phenol-formaldehyde polymer blend as template
No full text
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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