STATIN類降血脂藥物對血管平滑肌細胞之作用
動脈硬化是個致病率和致死率相當高的慢性發炎疾病,為台灣十大死因之一。在病理過程中血中濃度過高的膽固醇為動脈硬化的一大危險因子,其會誘發一連串的發炎反應驅使血管壁內皮細胞功能喪失,血壓上升,平滑肌細胞增生等。Statin 是臨床上十分有效的降血脂藥物,雖然其作用機制已知在於抑制膽固醇合成酵素 HMG-CoA reductase 而有降血脂功效,但近年來探討 statin 在抗發炎方面的作用也漸受重視。nitric oxide synthase (NOS) 代謝產物如 nitric oxide (NO),cyclooxygenase (COX) 代謝產物如 prostaglandin (PGE?、PGI?),及 heme oxygenase-1 (HO-1) 代謝產物如 carbon monoxide (CO),均有文獻指出可以改善血流,而可能在動脈硬化上扮演保護角色。相反的,matrix metalloproteinase (MMP) 的表現會誘使更多的免疫細胞浸潤到血管壁,並增加動脈硬化斑破裂,引起栓塞和中風的發生。在此實驗中,我們利用培養的大鼠主動脈血管平滑肌細胞作為研究材料,發現了 statin (lovastatin 、pravastatin、atorvastatin 、fluvastatin) 具有一些和降血脂無關的直接保護血管壁能力。包括會增加 interleukin-1β (IL-1β) 所誘導 iNOS 蛋白的表現及NO 的產生; statin 本身會增加 COX-2 和 HO-1 蛋白的表現及 PGE? 和PGI? 的產生,及抑制 MMP-2 和 MMP-9 蛋白活性的表現。此外分析調控 iNOS 基因轉錄最為關鍵的基因轉錄因子 NF-κB,發現適量的 statin 會增加 IL-1β 活化NF-κB 的作用。值得一提的是雖然適量 NO 有維持血管恆定的功能,過量時則會造成血壓過低休克的現象,這就是細菌感染後因內毒素 lipopolysaccharide (LPS) 作用引發敗血性休克的主要原因之一。為更進一步釐清 statin 是否會影響受細菌感染病人的生命危險,我們也探討 statin 對LPS 作用的影響。結果發現 statin 反而會抑制 LPS 誘導大量 iNOS 蛋白的表現,NO 的產生及 NF-κB 的活化。這些新的實驗結果提供更多證據支持 statin 可以藉由維持血管舒張,減緩血管壁的發炎反應,穩定動脈硬化斑的作用,以有效控制動脈硬化各個病程的進展。這發現能讓我們更透徹明白 statin 的作用,且對將來研發 statin 在心血管疾病方面新的臨床治療用途是有所助益的。 ;The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, statins, are potent inhibitors of cholesterol synthesis and have wide therapeutic use in cardiovascular diseases. Recent evidence, however, suggests that the beneficial effects of statins may extend beyond their action on serum cholesterol levels. In this study, we investigated the effects of lovastatin, pravastatin, atorvastatin, and fluvastatin on cultured rat vascular smooth muscle cells. We found statins can inhibit LPS-induced iNOS expression and NO production, while they can potentiate IL-1β-elicited responses. Moreover, statins themselves can stimulate COX-2 expression, PGE?, PGI? formation, and HO-1 induction. In contrast, statins can inhibit basal and IL-1β-induced enzyme activities of MMP-9 and MMP-2. In studying the activity of NF-κB, which plays an important role for iNOS gene induction, we found that statin can increase IL-1β-induced NF-κB activity, while inhibit that induced by LPS. All these results suggest that stimulation of iNOS expression in the presence of IL-1β, togeth1er with the increased COX-2 and HO-1 expression might contribute to the beneficial effects of statins in atherosclerotic process in terms of vasodilation and inhibition of smooth muscle cell proliferation. The inhibition of MMP activity might enhance plaque stability and reduce the development of atherosclerosis. All these results strengthen the pleiotropic actions of statins in anti-inflammation and anti-atherosclerosis.
步步為營
Two soldiers walk on a checkerboard. They can only walk one step once a time and two directions, front and left, are decided randomly. The gunshot is the column and row where a soldier is located, and one will die if he enters the gunshot area of the other. To treat the probability of winning, we first study the cases of 1×n, 2×n, 3×n, and 4×n rectangles iterately. Then we establish a general form of the probability of winning in a general n×k rectangle by using recurrence technique and generating function, respectively. Finally, we extend to the general n×m×k cuboid case to obtain the first soldier’s probability of winning.在一個長方形的棋盤中,兩士兵行走,每一次只走一步,而且上和左兩個方向是隨機的,射程範圍是所在的此行和此列,而進入他人射程範圍則死亡。探討其獲勝機率,從1×n 、2×n、3×n、4×n 矩形的情形逐步研究,並分別運用遞迴式的技巧及生成函數,導出 n×k 矩形中先走士兵獲勝機率的一般式。更進一步地,我們也獲得了n×m×k 立體空間先走士兵的獲勝機率。
低雷諾數圓形及多邊形水躍的研究
打開水龍頭,水鉛直落到正下方的水平板時形成圓形水躍。我們實驗研究20<Nr<150 的低雷諾數圓形水躍的變因,探討圓形水躍半徑和流量、出水口高度、以及液體黏滯係數間的關係。改用高黏滯係數的液體(4:1 的乙二醇水溶液),鉛直落入板上方深h 的相同液體時,先形成圓形,h 漸大時形成環形圓紋曲面,再加大h,形成多邊形水躍,內外圍同方向旋轉,轉速ω;液中加水,黏滯係數高於及低於某定值,多邊形都消失,側面觀察,外圍液體作鉛直面旋轉。將水平板改置於旋轉盤上方,使高黏滯係數(4:1)的乙二醇水溶液鉛直落入板上方形成多邊水躍,逐漸加快旋轉盤的轉速至 ω 時,多邊形都消失;逐漸減少乙二醇的濃度,至完全用水實驗,亦有多邊形出現,我們認為;平板上方的液體的轉動是非圓形水躍的成因。When a jet of water falls vertically on to a horizontal plate, it spreads out rapidly in a thin layer until it reaches a critical radius at which the layer depth increases abruptly. This phenomenon commonly called the circular hydraulic jump. We study the variations of the circular hydraulic jump radius, as a function of volume flow rate of the jet, the drop height, and the viscosity of the fluid at low Reynold numbers (20<Nr<150). When a jet of ethylene-glycol mixed with water (the kinetic viscosity is 10 times of water) falls on to a horizontal plate which is immersed in the same liquid with height h. We find the circular state frequently undergoes spontaneous breaking at its axial symmetry into a stationary polygonal shape. Rather than displaying the weak angular deformation generally seen in fluids, the jump forms clear corners and edges that are often straight. Several of these polygon formations show consistency in height h. And we find the polygon structure rotates in a horizontal motion. When a jet of water falls on to a horizontal plate, and the plate is rotated by a motor ,we find the axial symmetry of the free surface of circular hydraulic jump is spontaneously broken a various number of cornered polygonal shapes. We study the number of corners as a result of the volume flow rate of the jet, the drop height and the viscosity of the fluid in the experiment. And the frequency of rotation of the plate is taking into consideration.
水滴奇遇記-蓮花效應的真面目
Lotus self-cleaning effect arises because the leaves have the superhydrophobic surfaces. When rain falls onto a lotus leaf, water beads up as a result of surface tension. The water drops promptly roll off the surface, taking every dirt with them. This phenomenon is called the lotus effect. With the aid of a light microscope and an Environmental Scanning Electron Microscope, we observe and describe the morphology of the leaves of Nelumbo nucifera in detail. We successfully observe the real interface between air, water droplets and the papillae of a lotus leaf, and find the evidence of a composite surface that is formed by epicuticular wax crystals and air. These observations improve our understanding of the two-level composite surfaces that are formed by micro-scale papillae, nano-scale epicuticular wax crystals and air. We try the method of using the critical angle of a static drop beginning to roll on inclined surface to evaluate the self-cleaning ability. We then find out that it may be a more precise criterion compared to using the static contact angle for the evaluation of the lotus effect. Literature review shows that the earlier investigation lacks the height(H) and interval(I) of the projections on the lotus leaf surface. A close relationship between the self-cleaning property and the H/I ratio is found. In this study, we present the experimental data of the height and interval of the projections on four different species of plant leaves that all have lotus effect, which may be of great help to technological applications. 蓮花效應是指蓮葉表面具有超疏水性與自我潔淨的能力,當雨水落在葉面,因為表面張力的作用形成水珠,水滴迅速滾離葉面,把灰塵一起帶走。本實驗以光學顯微鏡和環境式掃描式電子顯微鏡觀察蓮葉,詳細描述其表面形態,成功的發現空氣、水滴和蓮葉乳突真實的接觸界面以及表面蠟和空氣構成複合表面的證據。實驗結果可以使乳突、奈米表面臘質和空氣構成的雙層次複合表面更容易被了解。我們嘗試以水滴傾斜滾動臨界角來評估自潔能力強弱,實驗結果比傳統使用靜止接觸角更為準確。表面高度和間距的比值與蓮花效應有很大的關係,查閱文獻顯示蓮葉缺乏這些資料,本研究提出四種有自潔能力的葉子的實驗數據,這些數據應該對科技應用有很大的幫助。
費瑪也瘋狂-平面上存在障礙時連接三定點的最佳網絡問題
在一個有障礙的平面上,給三個定點,我們探討連接此三點的最佳網絡。我們討論了諸如直線、射線、線段、圓、網格狀、三角形……等類的障礙,當網絡每穿越障礙一次,就必須付出代價,例如「拖延5 分鐘」。所以,設網絡穿越障礙的次數為y ,則網絡除了原本的總長度之外,還額外加入y 倍某固定數值的損耗。我們以費瑪點的各種性質及三角形不等式等方法為工具,就不同的穿越障礙次數綜合比較,而找出最佳網絡。在某些情況下,最佳網絡不是以費瑪點來連接三點,而是在障礙(如:直線)上找出符合某種與餘弦值相關特殊性質的點,以該點來連接三點,而此網絡可用GSP 軟體相當精確地作出。另外,我們也探討在考慮障礙造成損耗的情況下,兩點間的「實際距離」為何。 最後,我們考慮「混合障礙」問題。在此類問題中,除了前面所討論的障礙,還另加了如同「河流」的兩平行直線間區域之障礙,在這種障礙區域中,網絡的長度要乘以數倍來計算。我們發現,此類問題的最佳網絡也可用特定的正弦條件配合GSP 而相當精確地作出來。;Considering various kinds of obstacles in a plane, such as a line, a segment, a ray, a circle, a triangle or chessboard grids, which function like a red light, we research into the problem of finding the optimal network connecting three given points A, B, C in the plane amidst obstacles described above. Each time when the network crosses an obstacle, it will cause losses, such as five minute’s delay or a loss of one hundred dollars. Taking advantage of Fermat points, some basic inequalities concerning triangles and some special qualities about sine or cosine functions, we obtain the optimal networks in different situations. Besides, we consider what the “real distance” between two points is when there are obstacles in a plane. We also put another obstacle, including a line and a weighted region between two parallel lines, into consideration. In the region, like a river or a muddy ground in real life, the length of the network should be multiplied by a fixed time. Furthermore, we can use GSP to make the networks very accurately.