請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54078
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳林祈(Lin-Chi Chen) | |
dc.contributor.author | Ting-Hsien Wang | en |
dc.contributor.author | 王廷先 | zh_TW |
dc.date.accessioned | 2021-06-16T02:39:06Z | - |
dc.date.available | 2018-07-23 | |
dc.date.copyright | 2015-07-23 | |
dc.date.issued | 2015 | |
dc.date.submitted | 2015-07-23 | |
dc.identifier.citation | Reference
Aita, T., K. Nishigaki and Y. Husimi (2014). 'Estimation of statistical binding properties of ligand population during in vitro selection based on population dynamics theory.' Mathematical Biosciences 247: 59-68. Bai, H., R. Wang, B. Hargis, H. Lu and Y. Li (2012). 'A SPR aptasensor for detection of avian influenza virus H5N1.' Sensors 12(9): 12506-12518. Bock, C., M. Coleman, B. Collins, J. Davis, G. Foulds, L. Gold, C. Greef, J. Heil, J. S. Heiling, B. Hicke, M. N. Hurst, G. M. Husar, D. Miller, R. Ostroff, H. Petach, D. Schneider, B. Vant-Hull, S. Waugh, A. Weiss, S. K. Wilcox and D. Zichi (2004). 'Photoaptamer arrays applied to multiplexed proteomic analysis.' Proteomics 4(3): 609-618. Boeijen, M. (2013). 'Glycosylation of the influenza A virus hemagglutinin protein.' Chiang, H,-Y. (2014). Study of docking-based in silico post-SELEX minimization for H1N1 influenza DNA aptamers. Master thesis, National Taiwan University. Connors, K. A. and M. J. Jozwiakowski (1987). 'Studies on adsorptiochromism .1. binding of adsorptiochromic spiropyrans to some pharmaceutically useful solids.' Journal of Pharmaceutical Sciences 76(12): 892-897. Cox, J. C. and A. D. Ellington (2001). 'Automated selection of anti-protein aptamers.' Bioorganic & Medicinal Chemistry 9(10): 2525-2531. Cruz-Aguado, J. A. and G. Penner (2008). 'Determination of ochratoxin a with a DNA aptamer.' J Agric Food Chem 56(22): 10456-10461. De Vries, S. J., A. D. J. van Dijk, M. Krzeminski, M. van Dijk, A. Thureau, V. Hsu, T. Wassenaar and A. M. J. J. Bonvin (2007). 'HADDOCK versus HADDOCK: New features and performance of HADDOCK2.0 on the CAPRI targets.' Proteins- Structure Function and Bioinformatics 69(4): 726-733. del Toro, M., R. Gargallo, R. Eritja and J. Jaumot. (2008). 'Study of the interaction between the G-quadruplex-forming thrombin-binding aptamer and the porphyrin 5,10,15,20- tetrakis-(N-methyl-4-pyridyl)-21, 23H-porphyrin tetratosylate.' Anal Biochem 379(1): 8-15. Deng, Q., I. German, D. Buchanan and R. T. Kennedy (2001). 'Retention and separation of adenosine and analogues by affinity chromatography with an aptamer stationary phase.' Analytical Chemistry 73(22): 5415-5421. Di Primo, C. and I. Lebars (2007). 'Determination of refractive index increment ratios for protein-nucleic acid complexes by surface plasmon resonance.' Anal Biochem 368(2): 148-155. 82 Drabovich, A. P., M. Berezovski, V. Okhonin and S. N. Krylov (2006). 'Selection of smart aptamers by methods of kinetic capillary electrophoresis.' Analytical Chemistry 78(9): 3171-3178. Dua, P., S. Kim, et al. (2008). 'Patents on SELEX and therapeutic aptamers.' Recent Pat DNA Gene Seq 2(3): 172-186. Duhovny, D., R. Nussinov, H. J. Wolfson (2002). 'Efficient unbound docking of rigid molecules.' Algorithms in Bioinformatics, Proceedings 2452: 185-200. Durtschi, J. D., J. Stevenson,W. Hymas and K. V. Voelkerding (2007). 'Evaluation of quantification methods for real-time PCR minor groove binding hybridization probe assays.' Anal Biochem 361(1): 55-64. Eaton, B. E., L. Gold, B. J. Hicke, N. Janjic, F. M. Jucker, D. P. Sebesta, T. M. Tarasow, M. C. Willis and D. A. Zichi (1997). 'Post-SELEX combinatorial optimization of aptamers.' Bioorganic & Medicinal Chemistry 5(6): 1087-1096. Ellington, A. D. and J. W. Szostak (1990). 'Invitro Selection of Rna Molecules That Bind Specific Ligands.' Nature 346(6287): 818-822. Endoh, T., H. Funabashi, M. Mie and E. Kobatake (2005). 'Method for detection of specific nucleic acids by recombinant protein with fluorescent resonance energy transfer.' Analytical Chemistry 77(14): 4308-4314. Fagerstam, L. G., A. Frostellkarlsson, P. Karlsson, B. Persson and I. Ronnberg (1992). 'Biospecific interaction analysis using surface-plasmon resonance detection applied to kinetic, binding-site and concentration analysis.' Journal of Chromatography 597(1-2): 397-410. Fried, M. and D. M. Crothers (1981). 'Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis.' Nucleic Acids Res 9(23): 6505-6525. Garner, M. M. and A. Revzin (1981). 'A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system.' Nucleic Acids Res 9(13): 3047-3060. Gaurav, J., F. Boeckler, A. Joerger1 and A. Fersht1 'qPCR as a primary screen in drug discovery.' Gerstle, J. T. and M. G. Fried (1993). 'Measurement of binding kinetics using the gel electrophoresis mobility shift assay.' Electrophoresis 14(8): 725-731. Gokulrangan, G., J. R. Unruh, D. F. Holub, B. Ingram, C. K. Johnson and G. S. Wilson (2005). 'DNA aptamer-based bioanalysis of IgE by fluorescence anisotropy.' Analytical Chemistry 77(7): 1963-1970. 83 Gopinath, S. C., T. S. Misono, K. Kawasaki, T. Mizuno, M. Imai, T. Odagiri and P. K. Kumar (2006). 'An RNA aptamer that distinguishes between closely related human influenza viruses and inhibits haemagglutinin-mediated membrane fusion.' Journal of General Virology 87(3): 479-487. He, C.-Z., K.-H. Zhang, T. Wang, Q, -S. Wan, P. –P. Hu, M. -D. Hu, D. –Q. Huang and N. –H. Lv (2013). 'Single-primer-limited amplification: A method to generate random single-stranded DNA sub-library for aptamer selection.' Anal Biochem 440(1): 63-70. Huang, J. D. (1983). 'Errors in estimating the unbound fraction of drugs due to the volume shift in equilibrium dialysis.' Journal of Pharmaceutical Sciences 72(11): 1368-1369. Hybarger, G., J. Bynum, R. F. Williams, J. J. Valdes and J. P. Chambers (2006). 'A microfluidic SELEX prototype.' Anal Bioanal Chem 384(1): 191-198. Iliuk, A. B., L. H. Hu and W. A. Tao (2011). 'Aptamer in bioanalytical applications.' Analytical Chemistry 83(12): 4440-4452. Jaouen, S., L. de Koning, C. Gaillard, E. Muselikova-Polanska, M. Stros and F. Strauss (2005). 'Determinants of specific binding of HMGB1 protein to hemicatenated DNA loops.' J Mol Biol 353(4): 822-837. Jarocka, U., R. Sawicka, A. Gora-Sochacka, A. Sirko, W. Zagorski-Ostoja, J. Radecki and H. Radecka (2014). 'Electrochemical immunosensor for detection of antibodies against influenza A virus H5N1 in hen serum.' Biosensors and Bioelectronics 55: 301-306. Jian-umpunkul, P., C. Thepthai, N. Apiwat, W. Chantima, K. Poomputsa, N. Wiriyachaiporn and T. Dharakul (2012). 'Improved sensitivity of influenza A antigen detection using a combined NP, M, and NS1 sandwich ELISA.' Journal of virological methods 185(1): 24-31. Jing, M. and M. T. Bowser (2011). 'Methods for measuring aptamer-protein equilibria: A review.' Anal Chim Acta 686(1-2): 9-18. Johnson, B. B., K. S. Dahl, I. Tinoco, V. I. Ivanov and V. B. Zhurkin (1981). 'Correlations between deoxyribonucleic-acid structural parameters and calculated circular-dichroism spectra.' Biochemistry 20(1): 73-78. Kang, X., W. Wu, C. Zhang, L. Liu, H. Feng, L. Xu, X. Zheng, H. Yang, Y. Jiang and B. Xu (2014). 'Detection of avian influenza A/H7N9/2013 virus by real-time reverse transcription-polymerase chain reaction.' Journal of virological methods. Keefe, A. D., S. Pai and A. Ellington (2010). 'Aptamers as therapeutics (vol 9, pg 537, 2010).' Nature Reviews Drug Discovery 9(8). 84 Lai, Y.-T. and J. J. DeStefano (2011). 'A primer-free method that selects high-affinity single-stranded DNA aptamers using thermostable RNA ligase.' Anal Biochem 414(2): 246-253. Lee, W., A. Obubuafo, Y. I. Lee, L. M. Davis and S. A. Soper (2010). 'Single-pair fluorescence resonance energy transfer (spFRET) for the high sensitivity analysis of low-abundance proteins using aptamers as molecular recognition elements.' Journal of Fluorescence 20(1): 203-213. Li, Y., T. Wu, X. Qi, Y. Ge, X. Xuo, B. Wu, H. Yu, Y. Zhu, Z. Shi and H. Wang (2013). 'Simultaneous detection of hemagglutinin and neuraminidase genes of novel influenza A (H7N9) by duplex real-time reverse transcription polymerase chain reaction.' Journal of virological methods 194(1): 194-196. Liu, L. A. and P. Bradley (2012). 'Atomistic modeling of protein-DNA interaction specificity: progress and applications.' Curr Opin Struct Biol 22(4): 397-405. Liu, X., Z. Cheng, H. Fan, S. Ai and R. Han (2011). 'Electrochemical detection of avian influenza virus H5N1 gene sequence using a DNA aptamer immobilized onto a hybrid nanomaterial-modified electrode.' Electrochimica Acta 56(18): 6266-6270. Long, S. B., M. B. Long, R. R White and B. A. Sullenger (2008). 'Crystal structure of an RNA aptamer bound to thrombin.' Rna-a Publication of the Rna Society 14(12): 2504-2512. Ludwig, S., S. Pleschka and T. Wolff (1999). 'A fatal relationship—influenza virus interactions with the host cell.' Viral immunology 12(3): 175-196. Mapleson, W. W. (1987). 'Computation of the Effect of Donnan Equilibrium on Ph in Equilibrium Dialysis.' Journal of Pharmacological Methods 17(3): 231-242. Mendonsa, S. D. and M. T. Bowser (2004). 'In vitro evolution of functional DNA using capillary electrophoresis.' J Am Chem Soc 126(1): 20-21. Mendonsa, S. D. and M. T. Bowser (2004). 'In vitro selection of high-affinity DNA ligands for human IgE using capillary electrophoresis.' Analytical Chemistry 76(18): 5387-5392. Mendonsa, S. D. and M. T. Bowser (2005). 'In vitro selection of aptamers with affinity for neuropeptide Y using capillary electrophoresis.' J Am Chem Soc 127(26): 9382-9383. Miodek, A., H. Sauriat-Dorizon, C. Chevalier, B. Delmas, J. Vidic and H. Korri-Youssoufi (2014). 'Direct electrochemical detection of PB1-F2 protein of influenza A virus in infected cells.' Biosensors and Bioelectronics 59: 6-13. Mosing, R. K., S. D. Mendonsa and M. T. Bowser (2005). 'Capillary electrophoresis-SELEX selection of aptamers with affinity for HIV-1 reverse transcriptase.' Analytical Chemistry 77(19): 6107-6112. 85 Musheev, M. U. and S. N. Krylov (2006). 'Selection of aptamers by systematic evolution of ligands by exponential enrichment: addressing the polymerase chain reaction issue.' Anal Chim Acta 564(1): 91-96. Nienhaus, K. and G. U. Nienhaus (2005). 'Probing heme protein-ligand interactions by UV/visible absorption spectroscopy.' Methods Mol Biol 305: 215-242. Nonaka, Y., W. Yoshida, K. Abe, S. Ferri, H. Schulze, T. T. Bachmann and K. Ikebukuro (2013). 'Affinity improvement of a VEGF aptamer by in silico maturation for a sensitive VEGF-detection system.' Analytical Chemistry 85(2): 1132-1137. Oehler, S., R. Alex and A. Barker (1999). 'Is nitrocellulose filter binding really a universal assay for protein-DNA interactions?' Anal Biochem 268(2): 330-336. Ohuchi, S. P., T. Ohtsu and N. Nakamura (2006). 'Selection of RNA aptamers against recombinant transforming growth factor-beta type III receptor displayed on cell surface.' Biochimie 88(7): 897-904. Padmanabhan, K. and A. Tulinsky (1996). 'An ambiguous structure of a DNA 15-mer thrombin complex.' Acta Crystallographica Section D-Biological Crystallography 52: 272-282. Pavski, V. and X. C. Le (2003). 'Ultrasensitive protein-DNA binding assays.' Curr Opin Biotechnol 14(1): 65-73. Payungporn, S., P. Phakdeewirot, S. Chutininitkul, A. Theamboonlers, J. Keawcharoen, K. Oraveerakul, A. Amonsin and Y. Poovorawan (2004). 'Single-step multiplex reverse transcription-polymerase chain reaction (RT-PCR) for influenza A virus subtype H5N1 detection.' Viral immunology 17(4): 588-593. Perrin, F. (1926). 'The polarisation of flourescence light. Average life of molecules in their excited state.' Journal De Physique Et Le Radium 7: 390-401. Pinette, M. M., J. C. Rodriguez-Lecompte, J. Pasick, D. Ojkic, M. Leith, M. Suderman and Y. Berhane (2014). 'Development of a duplex fluorescent microsphere immunoassay (FMIA) for the detection of antibody responses to influenza A and newcastle disease viruses.' Journal of immunological methods 405: 167-177. Ryan, P. C., M. Lu, and D. E. Draper. (1991). 'Recognition of the highly conserved GTPase center of 23 S ribosomal RNA by ribosomal protein L11 and the antibiotic thiostrepton.' J Mol Biol 221(4): 1257-1268. Schneidman-Duhovny, D., Y. Inbar, R. Nussinov and H. J. Wolfson (2005). 'PatchDock and SymmDock: servers for rigid and symmetric docking.' Nucleic Acids Research 33: W363-W367. Schuck, P. (1996). 'Mass transport and kinetic analysis of ligand-receptor interactions as detected with an evanescent wave biosensor.' Biophysical Journal 70(2): Mp341-Mp341. 86 Tabarzad, M., B. Kazemi, H. Vahadi, R. Aboofazeli, S. Shahhosseini and N. Nafissi-Varcheh (2014). 'Challenges to design and develop of DNA aptamers for protein targets. I. Optimization of asymmetric PCR for Generation of a single stranded DNA library.' Iranian journal of pharmaceutical research: IJPR 13(Suppl): 133. Tasset, D. M., M. F. Kubik and W. Steiner (1997). 'Oligonucleotide inhibitors of human thrombin that bind distinct epitopes.' J Mol Biol 272(5): 688-698. Tsao, K.-C., Y.-B. Kuo, C. -G. Huang, S. –W. Chau and E. -C. Chan (2011). 'Performance of rapid-test kits for the detection of the pandemic influenza A/H1N1 virus.' Journal of virological methods 173(2): 387-389. Tsuji, S., T. Tanaka, N. Hirabayashi, S. Kato, J. Akitomi, H. Egashira, I. Waga and T. Ohtsu (2009). 'RNA aptamer binding to polyhistidine-tag.' Biochem Biophys Res Commun 386(1): 227-231. Tuerk, C. and L. Gold (1990). 'Systematic evolution of ligands by exponential enrichment - Rna Ligands to Bacteriophage-T4 DNA-Polymerase.' Science 249(4968): 505-510. Vater, A., F. Jarosch, K. Buchner and S. Klussmann (2003). 'Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: tailored-SELEX.' Nucleic Acids Res 31(21): e130. Wahlgren, J. (2011). 'Influenza A viruses: an ecology review.' Infection ecology & epidemiology 1. Wang, C., M. Zhang, G. Yang, D. Zhang, H. Ding, H. Wang, M. Fan, B. Shen and N. Shao (2003). 'Single-stranded DNA aptamers that bind differentiated but not parental cells: subtractive systematic evolution of ligands by exponential enrichment.' J Biotechnol 102(1): 15-22. Wang, R. and Y. Li (2013). 'Hydrogel based QCM aptasensor for detection of avian influenzavirus.' Biosensors and Bioelectronics 42: 148-155. Wang, R., J. Zhao, T. Jiang, Y. M. Kwon, H. Lu, P. Jiao, M. Liao and Y. Li (2013). 'Selection and characterization of DNA aptamers for use in detection of avian influenza virus H5N1.' Journal of virological methods 189(2): 362-369. Yang, D. -K., L. -C. Chen, M. –Y. Lee and C.-H. Hsu (2014). 'Selection of apatmersfor flourescent detection of alpha-methylacyl-CoA racemase by single-bead SELEX.' Biosensors and Bioelectronics. 87 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54078 | - |
dc.description.abstract | 經由系統配位子指數增益演繹程序(SELEX)所篩選出對目標蛋白分子具有專 一性辨識能力之核酸適體在流感病毒的快速篩檢上具有相當的潛力。然而,如何在 短時間及少量的蛋白質樣品消耗下找到高專一性與親合性的核酸適體序列一直是 核酸適體篩選研究中所遇到的瓶頸。本篇論文中,我們提出了一種利用微珠做為固定載體的有效率的核酸適體篩選方法。在此方法下,我們使用三種具有不同引子的 單股 DNA 資料庫對重組之 H5 血球凝集素進行核酸適體的篩選。其結果顯示,此 微珠載体之核酸適體序列篩選方式可有效的在早期的篩選迴圈(<4)便得到高度親 合性(~nM)且高度收斂(>90%)的單股 DNA 資料庫。在所篩選出的候選核酸適體序 列中,序列 ISP14 對 H5 血球凝集素具有卓越的親和力(45 pM),且經驗證後發現,ISP14 利用免疫型聚合酶連鎖反應(immuno-qPCR)方式在人類血清蛋白的干擾環境 下對 H5 血球凝集素的偵測極限(LOD)可達約 10-9 莫耳濃度,對於臨床的流感病毒偵測可為具有相當的潛力。此外,電腦模擬的分子嵌合結果中指出,此法所篩選出 之核酸適體序列與 H5 血球凝集素的結合位不盡相同,代表很有機會從此批核酸適 體篩結果中找出具有異位結合特性之核酸適體序列以提升流感病毒感測的靈敏度。 | zh_TW |
dc.description.abstract | Aptamers, single-stranded nucleotides selected through Systematic Evolution of Ligands by EXponential enrichment (SELEX) that recognize its target protein specifically, are now considered promising in rapid diagnosis of influenza virus. However, identifying high affinity and specificity aptamer sequences in short time at low sample consumption have always been the bottleneck of SELEX works. In this thesis, an efficient micro-beads based SELEX was demonstrated with 3 distinctly primered ssDNA libraries in screening of H5 ultra-sensing aptamers by using recombinant H5 hemagglutinin (HA) as the selecting target. The result indicated that the micro-beads based SELEX was capable of obtaining ssDNA pools with low dissociation constant (~nM) and high convergence (>90%) in very early round of selection (<4). Among the selected aptamer candidates, ISP14 possessed outstanding affinity (45 pM) to the HA and was also validated being able to perform immuno-qPCR based HA detection with nano-molar ranged LOD in presence of interfering HSA, which showed great potential in clinical influenza virus detection. Furthermore, the in silico docking result provided evidences that selected aptamers bind to different epitopes on HA, implying chance of finding bivalent aptamers with avidity effect, which may dramatically improve the sensitivity of influenza virus detection. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T02:39:06Z (GMT). No. of bitstreams: 1 ntu-104-R01631002-1.pdf: 7271255 bytes, checksum: 054284048a37411a00d40bbd1fb23c66 (MD5) Previous issue date: 2015 | en |
dc.description.tableofcontents | Contents
Abstract........................................................................................................................... i Chinese Abstract............................................................................................................. ii Content........................................................................................................................... iii List of Figures................................................................................................................. v List of Tables................................................................................................................. viii Chapter 1 Introduction .................................................................................................... .. 1 1.1. Research background ....................................................................................... .. 1 1.2. Objectives of the thesis .................................................................................... ...2 1.3. Strategy of this thesis ....................................................................................... .. 2 Chapter 2 Literature Review........................................................................................... .. 5 2.1. Aptamer and SELEX ....................................................................................... .. 5 2.2. In silico structure prediction and molecular docking ...................................... 11 2.3. Primer issue in aptamer selection .................................................................... 13 2.4. Affinity and specificity assay .......................................................................... 14 2.4.1 Separation based techniques .................................................................. 16 2.4.2 Mixture based techniques ...................................................................... 19 2.5. Influenza A and avian flu detection ................................................................. 23 Chapter 3 Material and Methods .................................................................................... 28 3.1. Apparatus and reagents .................................................................................... 28 3.2. Micro-beads based SELEX of anti-H5 aptamer .............................................. 33 3.2.1. ssDNA libraries design ......................................................................... 33 iii 3.2.2. Preparation of epoxide-functionalized glass microbeads (EGBs) ........ 34 3.2.3. Screening of antagonistic aptamer against recombinant H5 hemagglutinin ................................................................................................. 34 3.2.4. Sequencing and sequence alignment .................................................... 37 3.3. Identifying potential bivalent aptamer via in silico docking method .............. 42 3.4. Immuno-qPCR based affinity assay................................................................. 43 3.5. Limit of detection and specificity assay .......................................................... 47 Chapter 4 Result and Discussion .................................................................................... 49 4.1. The evolution of H5-binding ssDNA ligands monitored by differential qPCR analysis ................................................................................................................... 49 4.2. Affinity improvement of the ssDNA pools during anti-H5 SELEX ............... 60 4.3. In silico analysis of selected aptamer candidates ............................................ 63 4.3.1. Multiple sequence alignment and clustering ........................................ 63 4.3.2. Molecular docking with hemagglutinin ................................................ 67 4.4. Promising anti-H5 aptamer with superior affinity ........................................... 74 4.5. Nano-molar level hemagglutinin detection with immuno-qPCR method ....... 77 Chapter 5 Conclusions .................................................................................................... 80 Reference ........................................................................................................................ 82 Appendix ........................................................................................................................ 88 iv | |
dc.language.iso | en | |
dc.title | 應用多重SELEX資料庫篩選適體於高靈敏度免疫型qPCR禽流感H5感測之研究 | zh_TW |
dc.title | Ultra-sensitive Immuno-qPCR based Avian Influenza H5 Detection using Aptamers Selected from Multiple SELEX libraries | en |
dc.type | Thesis | |
dc.date.schoolyear | 103-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 劉?睿,周崇熙,陳倩瑜 | |
dc.subject.keyword | 核酸適體,微珠載体系統配位子指數增益演繹程序,H5 血球凝集素,免疫型qPCR,皮莫耳量級親和力,異位結合, | zh_TW |
dc.subject.keyword | aptamer,micro-beads based SELEX,H5 hemagglutinin,immuno-qPCR,pico-molar affinity,avidity, | en |
dc.relation.page | 93 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2015-07-23 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物產業機電工程學研究所 | zh_TW |
顯示於系所單位: | 生物機電工程學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-104-1.pdf 目前未授權公開取用 | 7.1 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。