1,721,273 research outputs found
Regulation of HIF-1α by osteopontin in glioblastoma cells
No full text人類惡性神經膠瘤,是最常見的原位性腦瘤,其特性是廣泛的浸潤到鄰近的正常腦組織。目前用來治療神經膠瘤的方法包含手術治療、傳統放射治療、或是化學藥物治療，但是都因為這項特徵而使得治療的效果有限。骨調素(osteopontin)是一種磷酸化的醣蛋白，一些癌細胞會過度分泌骨調素，而大量的骨調素與癌症的惡化有關。有文獻指出骨調素參與癌症的進程，例如異常的細胞分裂、細胞遷移、細胞侵入、和血管新生。除此之外，也有文獻指出在缺氧的情況下觀察到骨調素的表現增加。癌細胞在缺氧的情況下會藉由穩定缺氧誘導因子(HIF)來克服缺氧時所面對的壓力。基於以上的觀點，我們探討在神經膠瘤細胞中骨調素對HIF-1α表現的調控作用，並且探討disintegrin (HSA(C34S)-ARLDDL、PEG-ARLDDL)的抑制作用，這些disintegrins是從Rhodostomin中改變RGD domain附近胺基酸序列所獲得的衍生物，對αvβ3有專一性的拮抗作用。在本篇研究結果顯示人類神經膠瘤細胞U87在缺氧的情況下會促進骨調素的表現。外給骨調素會促使在缺氧下累積更多的HIF-1α蛋白,但不影響HIF-1αmRNA的表現，而osteopontin增加蛋白之表現會被disintegrin HSA(C34S)-ARLDDL所拮抗。此外，利用西方點墨法分析核內蛋白及免疫螢光染色證實骨調素會促進HIF-1α蛋白轉移到核內。更進一步發現，外給骨調素可以促進U87在缺氧下分泌更多的VEGF以及更嚴重的細胞侵入(invasion)，但是在給予disintegrin PEG-ARLDDL後便會抑制此U87的侵入行為。另外我們轉殖一小段具有專一性拮抗骨調素mRNA的RNA，可使骨調素的表現量下降。骨調素表現缺乏的U87細胞在CoCl2的刺激之下比起正常的U87細胞表現較少的HIF-1α蛋白，利用HRE-luciferase reporter assay也發現此種細胞有較少的HIF-1α轉譯活性。在缺氧的情況下骨調素缺乏的U87細胞比起正常的U87細胞有較少的細胞遷移 (migration)。此外，在骨調素缺乏的U87細胞中給予骨調素會恢復其HIF-1α的表現量，而此現象會被LY294002(PI3K的抑制劑)及SB203580(p38的抑制劑)所拮抗，進一步我們也觀察到外給骨調素會增加這些細胞中Akt、p38及FAK的磷酸化。
總結本篇的研究結果，我們發現在人類神經膠瘤細胞中給予骨調素會促進缺氧下所誘導的HIF-1α蛋白的堆積及細胞的侵入，在給予disintegrin後便可拮抗此作用。此外我們也證實了人類神經膠瘤細胞在缺氧的環境下骨調素與HIF-1α蛋白之間的關係。骨調素可能是藉由integrin、PI3K及p38這些訊息傳遞路徑來調控HIF-1α蛋白的表現。Human malignant gliomas, the most common primary brain tumors, are characterized by their ability to infiltrate to adjacent normal brain tissue. This infiltrative feature causes the limit effectiveness for present therapies including surgery, radiation therapy and chemotherapy. Osteopontin, a phosphorylated glycoprotein, is overexpressed in several cancers and correlates with tumor grade. Previous reports have indicated that osteopontin participates in tumor progression such as proliferation, migration, invasion, and angiogenesis. In addition, elevated osteopontin expression is observed following hypoxia, and tumor cells overcome hypoxia stress by the stabilization of hypoxia inducible factor (HIF) transcriptional regulators.
Based on these viewpoints, we investigated the effect of osteopontin on HIF-1α expression in glioblastoma, and explored the inhibitory effects of two kinds of αvβ3-selective disintegrins (HSA(C34S)-ARLDDL, PEG-ARLDDL) derived from the mutation of RGD neighborhood of Rhodostomin. It was found that the expression of osteopontin increased after exposure to hypoxia in U87 human glioma cells. Exogenous application of osteopontin enhanced hypoxia-induced HIF-1α protein expression, which was attenuated by the co-treatment with disintegrin HSA (C34S)-ARLDDL. Osteopontin at concentration of 3 ng/ml did not affect HIF-1α mRNA expression. In addition, we showed that application of osteopontin facilitated HIF-1α translocation to nucleus using nuclear extract Western blot analysis and also confirmed by the nuclear localization of HIF-1α using immunofluorescent staining. Furthermore, it was found that exogenous osteopontin enhanced hyoxia-induced VEGF secretion and facilitated U87 cell invasion, which was antagonized by the disintegrin of PEG-ARLDDL.
We further transfected U87 MG with a specific small hairpin RNA to knockdown osteopontin expression. Osteopontin-deficient U87 MG cells gave rise to less HIF-1α protein than control cells, and less HIF-1α transcriptional activity estimated by HRE-luciferase reporter assay after CoCl2 treatment. Osteopontin knockdown decreased the U87 MG cell migration under hypoxia. Furthermore, application of osteopontin to osteopontin-knockdown cells could reverse the HIF-1α expression, which was attenuated by the treatment of LY294002 (PI3K inhibitor) and SB203580 (p38 inhibitor). Moreover, exogenous osteopontin also increased the phosphorylation level of Akt, p38, and FAK.
In conclusion, osteopontin enhanced hypoxia-induced HIF-1α protein accumulation and invasion in human U87 glioma cells. Treatment of disintegrin could antagonize these effects. Moreover, a relationship between osteopontin and HIF-1α in glioblastoma cells under hypoxia treatment was demonstrated. The regulation of osteopontin on HIF-1α protein may act through integrin,PI3K, and p38 signaling pathways
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Application of Combined Electrochemical and Advanced Oxidation Processes on the Treatment of Dimethyl Phthalate
No full text本研究內容以電化學氧化程序(electrochemical oxidation process, EC)為基礎，並結合臭氧程序(electrochemical ozonation, EC/OZ)、光化學(photo electrochemical oxidation, EC/UV)及光電化學臭氧化程序(photo electrochemical ozonation, EC/OZ/UV)等高級氧化程序(advanced oxidation processes, AOPs)處理dimethyl phthalate (DMP)之研究。探討不同電壓(EV)、pH值及臭氧濃度(CO3, in)等參數對DMP分解效率(ηDMP)與總有機碳(total organic carbons, TOCs)去除率(ηTOC)之影響。
研究結果顯示，以EC程序處理DMP，EV = 4 volts (V)，反應時間(t)達80 min後，ηDMP = 8%，但僅將其分解形成其他有機副產物，無法將之礦化。使用EC/UV程序處理DMP於EV = 4 V, PUV = 100 Watts(W), t = 80 min時，其ηDMP及ηTOC分別為47.5及11.5%，較UV程序之30.4及5.7%為佳。提供CO3, in為10 mg L-1的O3及EV = 4 V，以EC/OZ程序處理DMP，於t = 80 min，其ηDMP及ηTOC分別可達94.4%及4.2%。若固定EV = 4 V，將CO3, in由10增加為16 mg L-1時，於t = 80 min時，ηDMP可提升至99%，且ηTOC可提高為30%。而EC/UV/OZ程序處理DMP，當EV = 4 V、PUV = 100 W及CO3, in = 10 mg L-1之條件下在60 min內，即可完全分解DMP，當t = 80 min後，ηTOC可達62.7%。若將CO3, in增加到30 mg L-1時，在t = 80 min後，其ηTOC可提升至88.3%。This study investigated the treatment of dimethyl phthalate (DMP) via various oxidation proesses such as 1) electrochemical oxidation (EC), 2) ozonation (OZ) with EC (EC/OZ), 3) ultraviolet (UV) with EC (EC/UV) and 4) photo ozonation with EC (EC/OZ/UV). The efficiencies of decomposition of DMP (ηDMP) and mineralization of total organic carbons (ηTOC) were evaluated under different operation voltages, pH values and concentrations of applied ozone (CO3, in).
The results showed that ηDMP is about 8% at reaction time (t) of 80 min, under the EC process with EV = 4 V. During the EC/UV process with EV = 4 V, PUV = 100 watts (W), the ηDMP and ηTOC are 47.5 and 11.5%, respectively. These are higher than 30.4 and 5.7% under UV process. However, the ability of oxidation in terms of ηTOC under EC process is too weak. For the EC/OZ process with EV = 4 V and CO3,in = 10 mg L-1, ηDMP and ηTOC are 94.4 and 4.2%, respectively, after t = 80 min. An increase of CO3, in from 10 to 16 mg L-1 further increases ηDMP to 99% and ηTOC to 30% after t = 80 min. As for the EC/UV/OZ process with Ev = 4 V, CO3, in = 10 mg L-1 and PUV = 100 W, the DMP was nearly completely decomposed at t = 60 min, while the ηTOC is 62.7% after t = 80 min. In case of CO3, in increased from 10 to 30 mg L-1, the value of ηTOC raises to 88.3% after t = 80 min
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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