重金屬錯影響細胞生理功能的研究
儘管鍺在電子工業上被廣泛運用，但對於暴露在鍺化合物所產生的毒害則尚未被詳細的探討。在探討鍺對細胞所產生的生理影響中，我們使用了二氧化鍺 ( GeO2）和有機鍺（ Ge-132 ）。由實驗結果顯示， GeO2，會造成人類子宮上皮癌細胞（ A 431 ) 及巨噬細胞株（ Raw264.7 ）死亡，而 Ge -132 對細胞生長則不造成任何影響，為了進一步了解鍺引起細胞死亡是否是經過細胞凋亡（apoptosis ) ，我們將鍺處理過的細胞進行染色體 D NA 的分析，結果發現細胞中 DNA 染色體沒有斷裂。由先前 Huang 等人於 1999 年的研究結果顯示，砷對細胞所造成的毒性是經由有絲分裂活化酵素（ MAPK ）傳導路徑，所以為了解鍺誘導細胞死亡的路徑，我們亦分析 MAPK 傳導路徑是否亦參與其中，我們發現 GeO2加入 A431 細胞後，會活化有絲分裂活化酵素中的 ERK ，但對JNK 及 p38 皆無影響，在對蛋白質表現方面，轉錄因子 c-Jun 的蛋白質表現也是隨著GeO2加入的時間增加而上升。 GeO2加入 Raw 264 . 7cell 後，會造成 JNK 、 ERK 的活化，同樣的轉錄因子 c- Jun 也會增加，由此一結果得知鍺對細胞的影響會因細胞的不同而有所差異，為了分析自由基是否參與砷及鍺所造成細胞死亡的過程，我們分析在 A431 細胞中可產生的 NO 的可誘導性 nitric oxide synthase ( iNOS ）的表現，我們發現氧化鍺及砷都會誘導 iNOS 的表現量增加。綜合以上結果，可能顯示氧化錯可能會經由 M A PK 訊息傳遞路徑來促使細胞的死亡，並且 iNOS 亦可能參與此過程。就我們所知，這是第一個提出重金屬所造成的毒害可能會經由 iNOS 來誘導產生的研究。
Despite the extensive use of germanium (Ge) in the electronic industry and optical devices, the potential risks of exposure to germanium compounds have not been evaluated. The effects of germanium on cell physiological functions were studied. We first asked if germanium oxide (GeO2) or carboxyethylgermanium (Ge-l32) could affect cell viability. We found that GeO2, but not Ge-l32, reduced cell viability in a dose-dependent manner in epidermoid carcinoma A43 I and macrophage Raw 264.7 cells. In order to test whether apoptosis contributes to germanium cytotoxicity, DNA fragmentation was evaluated in A43 1 and Raw 264.7 cells treated with GeO2 or Ge-132, respectively. We found that neither GeO2 nor Ge- 132 had effect on chromosomal DNA fragmentation. Previous studies by Huang (1999) et al indicated that sodium arsenite (NaAsO2) cytotoxicity is mediated through mitogen-activated protein kinase (MAPK) pathways. In order to study the mechanism(s) by which GeO2 mediates cell death, we analyzed the signal transduction pathways triggered by GeO2 We found that GeO2 stimulated the extracellular signal-regulated kinase (ERK) activity and transcription factor c-Jun in a time-dependent manner, but not c-Jun amino-terminal kinasc (JNK), or p38 MAPK in A431 cells. Treatment of the Raw 264.7 cells with GeO2, induced activities of ERK, JNK and c-Jun in a time-dependent manner. Collectively, these results suggested that GeO2 effects might be cell type specific. To test whether free radicals were involved in NaAsO2 or GeO2 mediated cell death, the expression of inducible nitric oxide synthase (iNOS), which produced the NO free radical, was determined in A431 cells treated with NaAsO2 or GeO2. We found that expression of iNOS was induced in a time-dependent manner in NaAsO2 or GeO2-treted A431 cells. Taken together, our results indicated that GeO2-induccd cell death may be mediated through MAPK signal pathways and that iNOS may contribute to NaAsO2 or GeO2 mediated cell death. To our knowledge, this is the first report that iNOS may contribute to heavy metal mediated cytotoxicity.
口琴簧片振動與氣流的影響
本研究主題在測量口琴簧片受到各種氣流因子影響後，所產生音色、音頻等變化之探討。在過去我們認為，一片簧片不論如何吹奏，其發出的頻率皆相同。但是事實上，演奏家控制氣流的強弱、方向、渦流等，便可吹奏出多樣的音頻。探討形狀因子對簧片頻率的影響，如：長度、寬度、厚度對頻率所造成的影響。自製口琴，利用變壓器控制送風機風速。探討氣流因子對簧片主頻之影響，利用各種不同的自製吹嘴，改變風速、角度、渦流…等，找出可能使簧片改變頻率的氣流因素。實驗結果發現改變風速會影響簧片主頻的變化，風速越大，頻率越大，為一條平滑線。但並非一直都會上升，當簧片頻率上升至某一極限，便無法再利用風速使頻率上升。例如實驗四吸音標準狀態下，風速大於8 Kt 後，頻率一直停在429Hz。在外加障礙物時(模擬吹奏舌頭時隆起)和標準狀態(正常零度入射)下頻率比較吹音和吸音有明顯的差異。吹音時，同風速下，其頻率比標準狀態高，發生音升；吸音時，同風速下，其頻率比標準狀態低，發生音降，具應用性。我們發現在頻率改變時，簧片的振動型態會有所不同，所以利用高畫素像機拍攝和電腦相位差算出簧片之曲折點至尾端的距離，發現頻率和簧片之曲折點至尾端的距離成正向關係。如實驗五中頻率從414 至419Hz，簧片的曲折點到振動端距離也明顯變大。我們發現吹嘴和口琴只要稍有一點空隙(大約在0.2cm 左右)，便會和完全吻合時有顯著的頻率差距(吻合後大約比有空隙低20Hz 左右)，此實驗頻率變化現象和現實壓音頻率變化極為相近。實驗過程中發現，改變簧片吹嘴的吻合程度，吹入口琴的風速相近，但頻率變化卻也有壓音的音頻變化。在實驗三加入各種氣流因子發現入射角度和標準情形差異不明顯，因此推論壓音的頻率變化和風力強度、入射角度關係不大，壓音主要為渦流所造成的現象。簧片振動模式改變，導致簧片振動頻率發生變化，且簧片的自然頻率不變。當壓音產生時，氣流在振動面造成妨礙簧片振動的抗力，但琴格內部同時也給簧片的風壓，使簧片產生一種非自然振動的頻率。The theme of the research is to explore the changes on its timbre and frequency after the harmonica reed is influenced by each kind of air current factor .In the past ,most people think no matter how to play the reed ,the frequency it produced was supposed to be the same. But in fact the frequency will be changeable under different direction, turbulent flow and air intension by the perform. First to explore the basic feature of harmonica reed, for example: The length, the width, thickness cause the influence on the frequency. To make the self-made harmonica, using the transformer control air feeder wind speed. To discussion the influenced caused by air current factors,and use each kind of different self-restraint to boast, change the wind speed, angle, turbulent flow ,in order to discover possible factors the reed causes to change the frequency of the air current factor. The experimental result discovered the change of wind speed can affect the change of basic frequency , the stronger speed cause the bigger frequency, It will be a curve. But it will not be rising continuously, when the reed frequency rise to some limit, it is unable to cause the frequency rise again by using the wind speed. For example experiment four sound absorption standard conditions, after the wind speed is higher than 8 Kt, the frequency continuously stops in 429Hz. To compare obstacle (simulation plays when tongue sticks out) and the standard condition (normal zero degree incidence) , comparison blows the sound agreement sound absorption to have the obvious difference. When blows the sound, under the same wind speed, its frequency is higher than the standard condition, has the sound to rise; When sound absorption, under the same wind speed, its frequency is lower than the standard condition, has the sound to fall. The harmonica terminology for presses the sound, extremely has the application. We discovered when frequency change, the reed vibration condition have differently, therefore use the camera photography and the computer phase different figures out the reed winding point to the end distance, discovered the frequency and the reed winding point relate to end distance is being connected. If tests five medium frequencies from 414 to 419Hz, the reed winding point is away from to the vibration end also obviously changes . The different reed vibration condition cause the frequency to change. Natural frequency is constant. When cause “bending” (the frequency is lower than the standard condition), the airflow make a force keep from reed vibration. But the chamber air pressure still drive reed. therefore cause the reed to give off not natural frequency sound