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.
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.
A Novel Procedure to Identify Genes involved in Electron Transfer of Exoelectrogens
Purpose of research. Microbial fuel cells (MFCs) are bioelectrochemical systems that generate electrical energy by exploiting the extracellular electron transport (EET) capabilities of electrochemically active bacteria (EAB) (Logan 2009). This investigation aims to identify genes involved in driving bacterial EET with a new procedure that enables rapid screening of a side array of genes. These insights may lead to improved MFC performance through enhancing reactor design or genetic engineering EABs (Alfonta 2009). Procedures. MFC metagenomic analysis. Twelve MFCs incubated with four different bacterial samples were operated for approximately one year. The bacterial DNA from before and after incubation was extracted and the 16S rRNA regions were PCR amplified and sequenced. The bacterial community changes were analyzed using the QIIME program to identify bacteria that were being selected. Fosmid Clone Isolation. An E. coli fosmid library (Mewis et al. 2013) that contained genes from EAB inferred in the previous step was incubated in three MFCs. After a 48 hour enrichment period, biofilm samples from the MFCs were extracted and individual clones were isolated and screened in the MFCs individually. An E. coli DH5α strain with no insert DNA was incubated separately as the control. DNA sequencing. Fosmid insert DNA from high-performing clones were extracted, purified using gel electrophoresis, constructed into sequencing libraries and sequenced. Bioinformatics Analysis. The sequences were constructed into larger contigs using the Velvet algorithm package. The open reading frames (ORFs) were inferred and translated into amino acid sequences and annotated with proteins identified from the KEGG, and SEEDs databases using Metapathways 2.5. Results. The changes in bacterial communities from the metagenomic analysis revealed increases in relative abundance in numerous genera from Firmicutes and Bacteroidetes. The MFCs incubated with the fosmid clones generated about 4 times more peak power than the MFCs incubated with the E. coli DH5α. Polarization curves generated for the MFCs demonstrated that the fosmid clones were able to sustain a higher current. Incubation of pure cultures of individual clones yielded four clones with significant performance improvements over the control strain. Protein data from Metapathways outputs reveled both novel and previously reported EET genes encoding for Type IV pilus structures, c-type cytochromes, soluble cytochromes, flavoproteins, and porins. Taxonomy inferences of the gene inserts by the Green Genes database reveal the genes most likely came from the same EABs that were inferred from the metagenomic analysis. Conclusions. The increased performance of the fosmid clone-powered MFCs suggest that the clones carried genes that enhanced their performance in the MFCs. This is further confirmed by polarization curves generated for the MFCs. The results of the taxonomy inferences suggest that the bacteria being selected for in the environmental samples carried genes that enhanced their performance in the MFCs, and that these genes were successfully identified in the subsequent steps. The results of this study demonstrate that using a gain of function approach to rapidly screen a wide array of genes in a gene library may be an efficient method to identify genes that enhance power generation of EABs in MFCs.
Parallelize it! 運算分享與系統自我校調
The research is about the optimal on parallel processing. Through boot disk – which will automatically finish booting configuration, .it is efficient and quick to build high performance PC clusters. The advantage of parallel computing could be applied to massive image processing. By sharing processing and breaking huge processing load into lots of pieces, we could get more efficient result. It is also possible to optimal parallel system through some special means such as dynamic configuration. Through the means, the system could distribute work loading itself. It could also adjust itself to get the highest performance and the most stable environment. 本研究之目的在於探討平行處理中的計算資源的最佳化，透過自動完成開機設定的Boot Disk 來有效快速建製出高效率的PC Clusters 環境，並透過動態配置與類神經網路的校調，使整體叢集的運算能自動調整至最佳化。平行處理優勢，可以應用在耗費極大量的運算資源的影像處理上。透過運算資源分享，可以以很高的效率將極為龐大的運算工作分散成許多較小的程序，使影像處理速度加快。經由平行演算法及實際應用的調整，可對已成形之平行系統作效能上的加強。使用類神經網路的方式訓練，使其系統能夠自我分配運算工作量，且隨著各平行化程式與各節點的不同，能自我校調至最佳化，達到高效率且穩定的運算環境。\r 本研究透過高效率且能自我調校的運算環境，可用於優化其本身結構，以達到\r 演化出更進一步系統，具有相當大的發展潛力。
「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.