La Belle et le Solitaire: Jeu de masques
為了解決Tomb mod 的問題，作者Cochet, Florence 這樣論述：
Nom: Marchesi Pr nom: Isabella Profession: cambrioleuse Mission: d rober l'OEuf de l'hiver, de Faberg Propri taire: Sir Stephen Hawkfield Localisation: Hawkfield Manor, Angleterre Risques: mod r s ... sauf si le ma tre des lieux d cide de l'entra ner dans un troublant jeu de masques... Du b
out de ses doigts tremblants d'impatience, elle retira le tissu. Ses yeux s' carquill rent. Un juron lui chappa. Le pr sentoir tait vide. Soit l'objet tait cach ailleurs, soit elle tait tomb e dans un pi ge. (Livre papier sans texte sur la tranche pour des raisons d' paisseur.) Mini-roman, 12
'000 mots environ.Épicurienne, Florence Cochet se laisse facilement tenter par une tablette de chocolat - suisse, évidemment ! -, une coupe de champagne ou un livre passionnant. (Les trois en même temps, c’est encore mieux.) Ses amis la disent fidèle, ironique, sincère et romantique, le tout form
ant un co*cktail parfois explosif... Elle ne peut que les croire. Au quotidien, elle conjugue les verbes aimer, enseigner et surtout, raconter. Elle écrit d’ailleurs toutes les histoires qui lui passent par la tête... et il y en a beaucoup.
Tomb mod進入發燒排行的影片
運用分子動力學模擬方法去探討在脂雙層內部之病毒管道蛋白的結構與動力
為了解決Tomb mod 的問題，作者柯孟明 這樣論述：
Utilizing the combination of powerful MD techniques and a fine-grained search protocol which search the conformational space consisting of distance, rotational angle, absolute angle, and tilt, the first part of this study focuses on developing models for monomeric as well as a hexameric bundle of
p7 protein from Hepatitis C Virus (HCV). It is a 63 amino acid polytopic membrane protein with two transmembrane domains (TMDs) and is involved in the modulation of electrochemical gradients across membranes within infected cells. Although there is a debate on the symmetry of the bundle architecture
, till date only a single structure of p7 is available in the database, which is hexameric in symmetry and is based on solution NMR experiment. Using evidence and predictions as mentioned above, an optimized protocol is proposed to generate in silico model of p7. The in silico model is the result of
combination of protein-protein docking method under MOE platform and MD simulation. This model is similar to one predicted by Patargias et al. (1) in the context of the symmetry and position of His-17, however the great difference between the two is the length of the helical motifs. Full length hel
ical motifs are taken into consideration in this study while it is not the case in the latter. Genotype-specific structural features of p7 have been investigated for the in silico model (genotype 1a) as well as the recently reported experimental monomeric and hexameric structures (genotype 1b and 5a
respectively). In addition to that, comparison of their channel gating behavior has been simulated. All the bundles tend to turn into a compact structure during MD simulations in hydrated lipid bilayers, as well as when simulated at ‘low pH’, which is proposed to trigger channel opening. Both the g
enotype 1a and 1b channel models are gated via movement of the parallel aligned helices, but the scenario for the genotype 5a protein is more complex, with a short N-terminal helix being involved. However, all bundles display pulsatile dynamics identified by monitoring water dynamics within the pore
.In the second part, dynamics of the generated model of hexameric p7 protein of genotype 1a is studied using sophisticated trajectory analysis method such as full correlation analysis (FCA) along with the experimentally established structure of genotype 5a. FCA is useful in identifying the correlate
d principal dynamics in a protein. Results of FCA reveals that though structural differences are there in both bundles they screen local minima during the simulation with the asymmetric collective motion of the protein domains. No ‘breathing-mode’-like dynamics is observed. The presence of divalent
ions, such as Ca-ions affect the dynamics of especially solvent exposed parts of the protein, but leave the asymmetric domain motion unaffected.Comparative study of the structural features and protein dynamics within membrane environment has been conducted on an already experimentally established st
ructure of M2 protein from Influenza A virus. It is a single TMD bitopic tetrameric protein with 97-amino acid residues and with N-terminus directed toward the viral exterior. It displays proton conductance and is activated by low pH environment as found in endosomes. The principal architecture of p
roton conductance in M2 channels is believed to lie within its TMDs, in the form of pore-lining conserved HXXXW motif. The decrease in the pH is mimicked by increasing the protonation state of the bundle in order to reenact the activation state. At lower pH, ions are found to enter through the C-ter
minal and travel to the vicinity of pore-lining conserved HXXXW motif. The fluctuation of the histidine ring system is found to increase at lower pH while it has hardly any effect on the overall protein dynamics.
探討胃幽門螺旋桿菌感染後所誘導的雌激素受器調控路徑
為了解決Tomb mod 的問題，作者胡伯宇 這樣論述：
本研究為探討胃幽門螺旋桿菌(Helicobacter pylori, H. pylori)感染所導致的胃癌中，人類雌激素受器(estrogen receptors, ERs)相關的分子調控機制。我們首先分析8片胃癌病人胃部組織的互補去氧核醣核酸微陣列晶片(cDNA microarray)以得到幽門螺旋桿菌與胃癌發生相關資料。在諸多幽門螺旋桿菌感染相關表現不同的基因裡，共有82個基因表現達兩倍以上。經Ingenuity Pathway Analysis (IPA) 軟體分析後共有41個基因與4組癌症調控網路高度相關，其中雌激素受器扮演調控網路中重要的中心角色(crucial hub)，並調控2
0個癌症相關基因。以即時定量反轉錄聚合酶連鎖反應驗證幽門螺旋桿菌感染的胃癌細胞株AGS的基因表現，發現共有14個與雌激素受器相關的基因表現量達1.5倍以上。此外我們與Human Genome-wide High-affinity ERE資料庫進行比對後，建立了新的幽門螺旋桿菌感染所引發的胃癌之分子調控路徑。更進一步的實驗分析包括細胞存活試驗(MTT assay)、細胞週期分析(cell cycle analysis)、抗氧化測試 (oxidative stress resistance test)、細胞侵犯實驗(invasion assay)、西方墨點轉漬法(western blot)、以及即
時定量反轉錄聚合酶連鎖反應。我們的結果顯示不論是1 nM 雌激素(estradiol)或10-5 M雌激素受體拮抗劑(estrogen receptor antagonist)法洛德(fulvestrant)均能有效減低AGS因幽門螺旋桿菌感染造成的增生、抗氧化力上升、和轉移能力。幽門螺旋桿菌會透過雌激素受器依賴(estrogen receptor dependent)的路徑使胃癌細胞生長、抗氧化、以及侵犯能力增加。以高生理濃度雌激素處理或用法洛德抑制胃癌細胞的雌激素受器能有效擾亂幽門螺旋桿菌感染所導致的各種不正常胃癌現象。我們的研究成果或許能為人類胃癌發生與進展調控機制帶來一線曙光。
