成人片色情影院www成全影视,亚洲人片在线观看天堂无码,国产亚洲精品美女久久久久,亚洲日韩激情无码一区,爱的阴暗面电影视频,宠媳无边免费完结小说,爱巢 1951 电影,成全电影大全在线播放,最新在线观看一区二区三区,性小说小雪

芬蘭Kibron專注表面張力儀測(cè)量技術(shù),快速精準(zhǔn)測(cè)量動(dòng)靜態(tài)表面張力

熱線:021-66110810,66110819,66110690,13564362870 Email: [email protected]

合作客戶/

拜耳公司.jpg

拜耳公司

同濟(jì)大學(xué)

同濟(jì)大學(xué)

聯(lián)合大學(xué).jpg

聯(lián)合大學(xué)

寶潔公司

美國(guó)保潔

強(qiáng)生=

美國(guó)強(qiáng)生

瑞士羅氏

瑞士羅氏

當(dāng)前位置首頁(yè) > 新聞中心

合成脂質(zhì)體類姜黃素納米粒子的自組裝——結(jié)論、致謝!

來(lái)源:上海謂載 瀏覽 1801 次 發(fā)布時(shí)間:2021-11-18

四、結(jié)論


核-殼納米顆粒(或粘土結(jié)構(gòu))的穩(wěn)定自組裝形成,姜黃素位于核中,納米粘土位于電暈中。粒子的典型尺寸為150 nm,表面帶負(fù)電(zeta電位~25 mV)。通過zeta電位(如圖3所示)、自組裝系統(tǒng)的能量(如圖5(B)和6(B)所示)、20天內(nèi)的恒定DLS計(jì)數(shù)率(如ESI?中的圖S3所示),確認(rèn)顆粒(由0.05%納米粘土形成)的穩(wěn)定性,以及20天后拍攝的SEM圖像的類似粒度分布(如ESI?中的圖S4所示)。組裝證明了疏水(核)和親水(殼)粒子與軟可調(diào)界面區(qū)共存。自組裝的主要原因是姜黃素納米顆粒之間的主要吸引力和納米粘土片提供的排斥力之間的復(fù)雜平衡。疏水區(qū)和親水區(qū)之間的界面區(qū)域在形成和穩(wěn)定過程中起著關(guān)鍵作用。它充分平衡了排斥屏障與姜黃素納米顆粒中普遍存在的疏水吸引力(如圖5(A)和6(A)所示),這阻止了姜黃素納米顆粒的聚集并導(dǎo)致粘粒組裝的形成。一些粘土顆粒的自組裝被發(fā)現(xiàn)對(duì)納米粘土團(tuán)的大小很敏感,因?yàn)樗{(diào)節(jié)了系統(tǒng)中的排斥力。對(duì)于這些結(jié)構(gòu)的穩(wěn)定形成,存在一個(gè)臨界閾值大小的納米粘土團(tuán)簇(L<80nm和s<100nm)。隨著粘土顆粒自組裝電位的增大,一些粘土顆粒的自組裝電位降低。簡(jiǎn)言之,我們最終證明,即使在沒有任何表面活性劑的情況下,當(dāng)相互作用力被調(diào)整以引起微妙的平衡時(shí),在無(wú)機(jī)粘土血小板存在的情況下也可以形成脂質(zhì)體樣結(jié)構(gòu)或穩(wěn)定的姜黃素納米粒。所形成的粘粒結(jié)構(gòu)在生物物理學(xué)領(lǐng)域可能有不同的應(yīng)用。粘土小體組件預(yù)計(jì)對(duì)系統(tǒng)的pH值敏感,因此它可能適用于將裝載在堆芯中的貨物運(yùn)送到目標(biāo)位置。

圖6足跡直徑對(duì)粘粒組件的影響。(A) 作為界面區(qū)域厚度函數(shù)的能量變化(L?60 nm,T?298 K,f?0.5,姜黃素納米顆粒半徑R?50 nm,疏水衰減長(zhǎng)度x0?1 nm,界面張力?40 mN m-1)。(B) 粘粒–粘粒相互作用作為粒間分離D的函數(shù),使用方程(5)計(jì)算。對(duì)于更大的封裝外形直徑,能量最小值變得更深,對(duì)于大于100 nm的s,能量最小值變得更有吸引力。


致謝


這項(xiàng)工作得到了尼赫魯大學(xué)授予NP的訪客獎(jiǎng)學(xué)金的支持。NP和KR承認(rèn)印度政府科學(xué)技術(shù)部的激勵(lì)教員獎(jiǎng)。我們感謝Akanksha Sharma博士在該大學(xué)高級(jí)研究?jī)x器設(shè)備的SEM測(cè)量方面提供的幫助。NP感謝Matthias Weiss教授的實(shí)驗(yàn)室設(shè)施和有用的討論。


參考


1 Y. Gao, C. Berciu, Y. Kuang, J. Shi, D. Nicastro and B. Xu, ACS Nano, 2013, 7, 9055–9063.


2 G. Helgesen, E. Svasand and A. T. Skjeltorp, J. Phys.: Condens. Matter, 2008, 20, 204127, DOI: 10.1088/0953-8984/20/20/ 204127.


3 M. Grzelczak, J. Vermant, E. M. Furst and L. M. Liz-Mirzan, ACS Nano, 2010, 4, 3591–3605.


4 A. K. Boal, F. Ilhan, J. E. DeRouchey, T. Thurn-Albrecht, T. P. Russell and V. M. Rotello, Nature, 2000, 404, 746–748.


5 Y. Xia, T. D. Nguyen, M. Yang, B. Lee, A. Santos, P. Podsiadlo, Z. Tang, S. C. Glotzer and N. A. Kotov, Nat. Nanotechnol., 2011, 6, 580–587.


6 G. M. Whitesides and B. Grzybowski, Science, 2002, 295, 2418.


7 E. E. Meyer, K. J. Rosenberg and J. Israelachvili, PNAS, 2006, 103, 15739–15746.


8 N. I. Lebovka, Adv. Polym. Sci., 2014, 255, 57–96.


9 A. S. Iglesias, M. Grzelczak, T. Altantzis, B. Goris, J. PerezJuste, S. Bals, G. V. Tendeloo, G. V. Stephan, H. Donaldson Jr, B. F. Chmelka, J. N. Israelachvili and L. M. Liz-Marzan, ACS Nano, 2012, 12, 11059–11065.


10 A. Laouini, C. Jaafar-Maalej, I. Limayem-Blouza, S. Sfar, C. Charcosset and H. Fessi, J. Colloid Sci. Biotechnol., 2012, 1, 147–168.


11 T. M. Allena and P. R. Cullis, Adv. Drug Delivery Rev., 2013, 65, 36–48.


12 M. J. Ostro and P. R. Cullis, Am. J. Hosp. Pharm., 1989, 46, 1576–1587.


13 A. Samad, Y. Sultana and M. Aqil, Curr. Drug Delivery, 2007, 4, 297–305.


14 P. da Silva Malheiros, D. J. Daroit and A. Brandelli, Trends Food Sci. Technol., 2010, 21, 284–292.


15 Z. Nie, A. Petukhova and E. Kumacheva, Nat. Nanotechnol., 2010, 5, 15–25.


16 E. Busseron, Y. Ruff, E. Moulin and N. Giuseppone, Nanoscale, 2013, 5, 7098–7140.


17 M. Rad-Malekshahi, L. Lempsink, M. Amidi, W. E. Hennink and E. Mastrobattista, Bioconjugate Chem., 2016, 27, 3–18.


18 R. M. Gorgoll, T. Tsubota, K. Harano and E. Nakamura, J. Am. Chem. Soc., 2015, 137, 7568–7571.


19 W. Lewandowski, M. Fruhnert, J. Mieczkowski, C. Rockstuhl and E. G′orecka, Nat. Commun., 2015, DOI: 10.1038/ ncomms7590.


20 M. M. Yallapu, M. Jaggi and S. C. Chauhan, Curr. Pharm. Des., 2013, 19, 1994–2010.


21 Y. Manolova, V. Deneva, L. Antonov, E. Drakalska, D. Momekova and N. Lambov, Spectrochim. Acta, Part A, 2014, 132, 815–820.


22 P. Anand, A. B. Kunnumakkara, R. A. Newman and B. B. Aggarwal, Mol. Pharm., 2007, 4, 807.


23 H. Hatcher, R. Planalp, J. Cho, F. M. Torti and S. V. Torti, Cell. Mol. Life Sci., 2008, 65, 1631.


24 Y. Zhang, C. Yang, W. Wang, J. Liu, Q. Liu, F. Huang, L. Chu, H. Gao, C. Li, D. Kong, Q. Liu and J. Liu, Sci. Rep., 2016, 6, 1– 12.


25 X. Yang, Z. Li, N. Wang, L. Li, L. Song, T. He, L. Sun, Z. Wang, Q. Wu, N. Luo, C. Yi and C. Gong, Sci. Rep., 2015, 5, 1–15.


26 D. Wang, S. M. Veena, K. Stevenson, C. Tang, B. Ho, J. D. Suh, V. M. Duarte, K. F. Faull, K. Mehta, E. S. Srivastan and M. B. Wang, Clin. Cancer Res., 2008, 14, 6228–6236.


27 V. Gupta, A. Aseh, C. N. Rios, B. B. Aggarwal and A. B. Mathur, Int. J. Nanomed., 2009, 4, 115–122.


28 R. K. Das, N. Kasoju and U. Bora, Nanomedicine, 2010, 6, 153– 160.


29 S. Bisht, G. Feldmann, S. Soni, R. Ravi, C. Karikar, A. Maitra and A. Maitra, J. Nanobiotechnol., 2007, 5, 3–21.


30 Y. He, Y. Huang and Y. Cheng, Cryst. Growth Des., 2010, 3, 1021–1024.


31 Bhawana, R. K. Basniwal, H. S. Buttar, V. K. Jain and N. Jain, J. Agric. Food Chem., 2011, 59, 2056–2061.


32 N. Pawar and H. B. Bohidar, Colloids Surf., A, 2009, 333, 120– 125.


33 B. Ruzicka, E. Zaccarelli, L. Zulian, R. Angelini, M. Sztucki, A. Moussaid, T. Narayanan and F. Sciortino, Nat. Mater., 2011, 10, 56–60.


34 R. K. Pujala, Dispersion Stability, Microstructure and Phase Transition of Anisotropic Nanodiscs, Springer Thesis, 2014, DOI: 10.1007/978-3-319-04555-9.


35 A. Faghihne jad and H. Zeng, Langmuir, 2013, 29, 12443– 12451.

合成脂質(zhì)體類姜黃素納米粒子的自組裝——摘要、介紹

合成脂質(zhì)體類姜黃素納米粒子的自組裝——材料和方法

合成脂質(zhì)體類姜黃素納米粒子的自組裝——結(jié)果和討論

合成脂質(zhì)體類姜黃素納米粒子的自組裝——結(jié)論、致謝!

{????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}| {????′ê}|