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Asymmetric Total Synthesis of GlaxoSmithKline’s Potent Phosphodiesterase PDE IVb Inhibitor

Phosphodiestarase of subtype PDE IVb inhibitors are considered as perspective drugs for the treatment of the central nervous system disorders (depression, Alzheimer’s disease, Parkinson’s disease). Pyrrolizidinone Glaxo-1, proposed by GlaxoSmithKline, is a highly potent PDE IVb inhibitor (IC50 = 63 nM), then conventional phosphodiesterase inhibitors Ro-20-1724, Rolipram and Cilomilast. However the activity of the Glaxo-1 was studied on a racemic sample, since the asymmetric approach to its synthesis has not been developed. Therefore the purpose of this research was the development of an efficient synthetic scheme enabling enantioselective excess to both (-)- and (+)-Glaxo-1, which can be than subjected to biological studies. \r The key stage in proposed asymmetric synthesis (-)- and (+)-Glaxo-1 is stereoselective [4+2]-cycloaddition of the nitroolefin to an optically activity vinyl ethers, derived from (-)- or (+)-trans-2-phenylcyclohexanols. The resulting chiral cyclic nitronates are transformed into a functionalized cyclic oxime ethers using tandem sylilation-nucleophilic substitution procedure. Reduction and decarboxylation of these products lead to optically pure Glaxo-1 and the regeneration of chiral 2-phenylcyclohexanols (91%). \r Thus both enantiomers (+) and (-)-Glaxo-1 were obtained selectively in average yield 12% from isovaniline and nitroethane. The study of biological profiles of each enantiomer of Glaxo-1 will be conducted in near future.

一后多夫否?黑棘蟻(Polyrhachis dives)聚落生殖策略之研究

A vast amount of research has been conducted on various ant species such as Monomonum pharaonis, Formica rufa, and Lasius niger, demonstrating the coexistence of polygyny and monogyny colonies. In polygyny colony, the high heredity variability of filial generation could be expected, but what could the monogyny colony do to hold the high heredity variability in order to increase the fitness? I hope I can account the sex ratio in the colony of spiny weaver ants, Polyrhachis dives, and compare the different colony with different reproductive strategies. I also want to check by V8 that the colony can form a polygyny colony and virgin queens can mate with many males of the same colony in the artificial nest. The results suggest that in the colony of spiny weaver ants, the higher the number of the dealate queens, the lower the number of the male. In the monogyny colony, workers control the sex ratio. According to the observation, we can see the alate adult mate in the artificial nest, and multimating can be recorded for the first time. The following study was there for undertaken to examine what’s the aftereffect made by the Reproductive strategies of polygyny colony and monogyny colony.在多后聚落內,子代變異度高是可以預期的,但是單后聚落中,又如何維持遺傳的變異度以增加其對環境的適應力呢?我們希望能計算黑棘蟻聚落組成,比較不同生殖策略的聚落之各種性比,並且錄影證實黑棘蟻聚落可以為多后聚落並進行巢內自交。我們發現:黑棘蟻聚落內,蟻后數愈高,則雄蟻比例較低;單后聚落之性比決定於工蟻;而根據錄影觀察,聚落中的有翅生殖族可在人工蟻巢中完成交配,多次交配的現象首次被實地紀錄,並且佔所有交配新生蟻后的92.8%。本實驗可利用黑棘蟻來了解單后與多后聚落的生殖策略對其族群發展的影響。

Mechanisms of Tumor Cell Invasion: The Role of Stat3 in Squamous Cell Carcinoma

Skin cancer, including basal cell and squamous cell skin carcinoma, is known to\r be the most common cancer type. Skin cancer is thought to make up half of all known\r cancers. Over one million non-melanoma skin cancers (NMSC) are reported every year. \r Approximately 300,000 of these cases are squamous cell carcinoma (SCC). It is\r estimated that about 2,000 people die from NMSC each year. Of the two skin cancer\r types, SCC tends to be the more clinically aggressive and likely to spread and invade,\r typically by way of blood or lymphatic vessels. Understanding the signaling pathways\r in SCC cells that regulate invasion will be important for developing improved cancer\r treatments. The signal transducer and activator of transcription 3 (Stat3) protein is a\r central regulator of numerous cellular activities, including proliferation, survival, and\r motility. Stat3 also has enhanced activity in many cancers, including skin SCC. This\r study shows that Stat3 regulates several invasive properties in a human skin SCC cell culture model.\r HGF (hepatocyte growth factor)- induced cell schattering was assessed for\r SRB12-p9 cells (p9WT), a human skin SCC cell line, along with SRB12-p9 cells\r engineered to have reduced Stat3 activity. Next, a cell viability-based adhesion assay\r was performed with these cells. Finally, severe combined immunodeficient (SCID)\r mice were injected subcutaneously with P9WT and S3DN cells and tumors were\r measured twice weekly. Extracted tumors were analyzed by immunohistochemistry and Western blotting for expression of the invasion related enzyme, MMP-2 and MMP-9.\r The suppression of Stat3 activity in S3DN cell lines resulted in reduced motility,\r greater adhesion, and a less invasive phenotype in SCID mice. Immunohistochemistry and Western blotting indicated higher levels of MMPs in the P9WT cells with\r expression localization towards the outer perimeter of the tumors. This data suggests\r that Stat3 plays a role in skin SCC invasion and better understanding of Stat3 function\r could lead to improved treatment and prevention of the disease.

關於二元根樹上的鏈、反鏈、獨立集的計數及極值

二元根樹是資訊科學上最重要的結構之一,因此其結構的探討就很有價值。在這個研究中,我們探討二元根樹上反鏈(Antichain),鏈(Chain),獨立集(Independent set)計數。在每一個子題之下,我們求出計算反鏈,鏈,獨立集的方法。之後我們求出極值(包括最大跟最小值),並且討論該極值之下所有可能的樹形。此外,我們並討論要列出二元根樹上這些資料(反鏈,鏈,獨立集)所需的演算法。In this paper we enumerate the number of antichains, chains, and independent sets of a binary tree of size n. After that we focus on the extreme values (maximal/minimal). we calculate the extreme values and discuss the possible graphs of trees when achieving these extreme values. Moreover, we offer algorithms for listing all the objects in each extreme case.

大氣層厚度光學測量法之研究及創新

這個專題研究的目的是要發展出一套簡單可靠的方法和廉價自製的器材,在地面上即能有效估測大氣層的厚度。我們小組研究光學中雷氏(Rayleigh)散射的原理,針對空氣分子對光線散射作用和特定方向之偏極效應,利用一已知散射長度之路徑,測量其偏極光的強度,同時比對由大氣層散射而來,在同一偏極面上的散射光強度,即能估算大氣層的厚度,方法簡單新穎,自製器材經實際測量和改進,有發展和推廣的價值。\r The main idea of the experiment is to set a system in order to effectively estimate the thickness of the atmosphere. On the theory of “Rayleigh Scattering” (small air molecules sizing about 10-4μm), we developed an equipment that has two tubes. The tubes lead the scattered lights from two paths. One is called “air light” scattered in the ground air, and the other “sky light” is scattered in the sky and reflected by a beam splitter. The two paths are on the same plane; the scattered lights are perpendicular to the direction of sunlight and 100% polarized. We could adjust and measure the distance “d” of the air light path. We simultaneously observe and compare the intensity of the lights from the two paths with the electronic instrument made by ourselves. By using the known distance “d” and the reflection “x” of the beam splitter, we can calculate the thickness of the atmosphere. The experiment is simple, novel and easy to do in an extensive field at school. Researchers don’t have to use a bloom, radar or satellite to discover the atmosphere, but you could use a simple equipment to observe the features of it.

吸〝氣〞大法-QCM 對有機氣體之吸附與偵測

中文摘要:\r 化學實驗中,常常會使用到各種具有揮發性的有機溶劑,如醇類、酸類、醛類及酮類等。\r 當吸入過量的揮發性有機溶劑時,將會對人體造成嚴重的傷害,故使用時格外需要留意。有\r 鑑於此,我們開始著手研究如何偵測氣相中的有機氣體分子。\r 本研究中,我們利用聚苯胺薄膜吸附氣體分子的特性並結合對質量變化極靈敏的石英晶\r 體微天平,自行設計了一套簡單、藥品用量少且不需昂貴儀器的實驗系統。藉由此系統,我\r 們有效的針對各種揮發性有機溶劑進行偵測,並進一步地探討不同氣體分子對於聚苯胺薄膜\r 的吸附現象。\r \r 英文摘要:\r Students usually use volatile organic solvent in laboratorys such as alcohols, carboxylic acids,\r aldehydes, ketones, etc. It will injure our body when we breathe in too much volatile organic\r solvent. For this purpose, we begin to study how to detect volatile organic compound in air.\r In this work, we combine polyaniline membrane which can adsorb gas molecules and quartz\r crystal microbalance which is highly sensitive to mass changes to design a simple and inexpensive\r system which needs only little chemicals. With this system, we can effectively detect different\r volatile organic compounds. Furthermore, we can also study the adsorption of polyaniline\r membrance for different volatile organic compounds.

「金」枝「玉」葉—金奈米與葉綠素的交互作用

本實驗在探討,當金奈米粒子和植物中的葉綠素產生鍵結作用力時,能量轉移的結果是否能幫助葉綠素激發電子。經由兩者混合後光譜的變化,發現兩者之間發生能量轉移。為探討此轉移現象和濃度的關係,我們將大小不同的金奈米和不同毫升數的葉綠素作用,並將其結果和金奈米與葉綠素的吸收強度和作比較,使用正規化的計算方法算出比值,由此看出兩者之間能量轉移的效率。當金顆粒約大於30nm時,正規化的數值隨的葉綠素濃度的增加而變大;而當金奈米顆粒約小於30nm時,則隨著葉綠素的增加而變小。Much attention is currently focused on chromophoric molecules because they can not only mimic natural antenna systems but also exhibit unique optical and physical properties. Chlorophyll , produced by extracting from green leaves, has electrostatic interactions with Au nanoparticles through carboxyl groups. Herein, we report the charge transfer between chlorophyll and Au nanoparticles using UV-vis electronic absorption spectroscopy. The efficiency of charge transfer from chlorophyll to Au nanoparticles was estimated by the normalization of Q-ban absorption intensity. From the observation of absorption intensity versus concentration of chlorophyll curves, we find that the efficiency of charge transfer is increased while the size of Au-particle is larger than 30nm, but decreased while the size smaller than 30nm.

傑克船長的心機

傑克船長和他的海盜們掠奪到許多箱珍寶,每箱含有數量不等的金幣及鑽石。船員們深怕傑克船長又出什麼陰謀,一致同意讓船長任選一半的箱子拿走。\r 當然,傑克不知道金幣和鑽石的價格比,為了保證可以得到一半的利益,傑克希望他拿到的金幣和鑽石都各占一半。傑克的願望會實現嗎?\r 這個問題已用高等數學證明其解,而本研究利用初等數學的方法,除證明傑克需取的最少箱子數外,同時也能更快速的算出取法。\r 類似的結果可應用至分配災區物資等情形,或任何無法轉移、獨立的資源,如各式專長的人才、多功能的機械等,期望可對更有效的分配做出貢獻。

DNA Detection by EGFET using GaN Nanowires Gate

DNA感測器近年來蓬勃發展,應用層面包括基因工程,醫學及藥物的開發等,然而目前較常使用的感測方法,需要繁瑣耗時的標定過程,且所使用的化學藥劑對環境容易造成傷害,鑒於以上方法的不完善處,我們決定設計一套新的感測系統,此研究結合了氮化鎵奈米線(GaN Nanowires)及延伸場效電晶體(EGFET)的優點,成功的發展出創新的DNA感測系統,氮化鎵奈米線的高生物匹配性及高感測面積,能有效提高靈敏度,延伸式場效電晶體的設計,史感測器具由免標定及時感測的特性,且易於組裝及操作,我們將探針DNA(probe DNA)修是在氮化鎵奈米線作為之延伸閘極上,由於DNA在中性水溶液中帶負電,且DNA之間具有強烈的互補特性,因此當目標DNA(target DNA)與探針DNA接合,形成雙股DNA,氮化鎵奈米線(閘極)的表面電位即會有所變化,並造成FET特性的改變,藉由此性質及能成功感測DNA,研究結果顯示,此研究所發展出的DNA感測器,愈有相當高的靈敏度(10-18),相較於其他以FET技術所設計出的DNA感測器,靈敏度提升了三個數量極,此外此感測器亦具有高選擇性,即使單一鹼基對的突變也能成功辨別;-hybridization based detection techniques are widely developed due to their promising applications in genetics, medicine and drug discovery. However, current DNA detection techniques based on labels or reagents are time-consuming, environmentally-harmful and complex to implement. In this study, we have successfully demonstrated a label-free extended-gate-field-effect-transistor (EGFET) sensor utilizing a GaN-nanowires electrode with DNA probes immobilized, capable of specific DNA sequence identification. The principle behind the design is based on the change in surface potential and charge transfer after hybridization. GaN nanowires, being bio-compatible, provide direct transfer path and high surface area, thus offer an unprecedented opportunity of DNA sensing with high sensitivity. In addition, our EGFET design facilitates easy assembly and operation of DNA detection. Comparative studies on complementary and non-complementary DNA were performed to verify the specificity of the sensor. By adapting GaN nanowires structure, the assay time of DNA was shorten to within thirty minutes. Moreover, our sensor displayed an ultra-high sensitivity in the level of attoM: three orders of magnitude higher in resolution than that of other FET-based DNA detection methods.

氣泡在黏滯性液體中的運動

本研究目的在探索不同大小之氣泡在不同黏滯性液體中運動情形。實驗結果發現大氣泡向上運動的速度較大,其下方會漸漸向內凹。並且觀察到氣泡間結合時的相互作用:氣泡在相同黏滯性膠水中上升時,若下方氣泡體積較大,其較快的速率會使距離縮短。此時小氣泡的下半向內凹,大氣泡的下半則向外呈現流線型尖端並且在接近小氣泡時速率增加,最後與小氣泡結合。若上方氣泡體積很小,與下方大氣泡的距離縮短至相互貼合,小氣泡會先停留在大氣泡的上半表面,再沿大氣泡表面下滑至大氣泡的下半才與大氣泡結合。This research traces the motions of bubble with different volume in viscid liquid. The experimental results show that the bigger bubble rises at faster speed. The shape of the small bubble is round. As the volume of the bubble increases, it turns hamburger-like. And if the bubble is big enough, its underside would be concaved. In viscid liquid, the speed of the bubble is not smooth but waved. The smaller the bubble is, the more the variation in speed is. The interaction of two bubbles is also studied. There are two types of the combination of two bubbles. While the big one closes to the small one, it is accelerated. The underside of the small one becomes concave. And the big one becomes streamline shape. If the difference in volume between two bubbles is significant, the small one slides along the surface of the big one, and goes into the concave beneath it, then combines with it.