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An Integrated Approach For Uncovering Novel DNA Methylation Biomarkers For Non-small Cell Lung Carcinoma

為了解決進擊的巨人 特殊能力的問題，作者VAIBHAV KUMAR SUNKARIA 這樣論述：

Introduction - Lung cancer is one of primal and ubiquitous cause of cancer related fatalities in the world. Leading cause of these fatalities is non-small cell lung cancer (NSCLC) with a proportion of 85%. The major subtypes of NSCLC are Lung Adenocarcinoma (LUAD) and Lung Small Cell Carcinoma (LUS

C). Early-stage surgical detection and removal of tumor offers a favorable prognosis and better survival rates. However, a major portion of 75% subjects have stage III/IV at the time of diagnosis and despite advanced major developments in oncology survival rates remain poor. Carcinogens produce wide

spread DNA methylation changes within cells. These changes are characterized by globally hyper or hypo methylated regions around CpG islands, many of these changes occur early in tumorigenesis and are highly prevalent across a tumor type.Structure - This research work took advantage of publicly avai

lable methylation profiling resources and relevant comorbidities for lung cancer patients extracted from meta-analysis of scientific review and journal available at PubMed and CNKI search which were combined systematically to explore effective DNA methylation markers for NSCLC. We also tried to iden

tify common CpG loci between Caucasian, Black and Asian racial groups for identifying ubiquitous candidate genes thoroughly. Statistical analysis and GO ontology were also conducted to explore associated novel biomarkers. These novel findings could facilitate design of accurate diagnostic panel for

practical clinical relevance.Methodology - DNA methylation profiles were extracted from TCGA for 418 LUAD and 370 LUSC tissue samples from patients compared with 32 and 42 non-malignant ones respectively. Standard pipeline was conducted to discover significant differentially methylated sites as prim

ary biomarkers. Secondary biomarkers were extracted by incorporating genes associated with comorbidities from meta-analysis of research articles. Concordant candidates were utilized for NSCLC relevant biomarker candidates. Gene ontology annotations were used to calculate gene-pair distance matrix fo

r all candidate biomarkers. Clustering algorithms were utilized to categorize candidate genes into different functional groups using the gene distance matrix. There were 35 CpG loci identified by comparing TCGA training cohort with GEO testing cohort from these functional groups, and 4 gene-based pa

nel was devised after finding highly discriminatory diagnostic panel through combinatorial validation of each functional cluster.Results – To evaluate the gene panel for NSCLC, the methylation levels of SCT(Secritin), FOXD3(Forkhead Box D3), TRIM58(Tripartite Motif Containing 58) and TAC1(Tachikinin

1) were tested. Individually each gene showed significant methylation difference between LUAD and LUSC training cohort. Combined 4-gene panel AUC, sensitivity/specificity were evaluated with 0.9596, 90.43%/100% in LUAD; 0.949, 86.95%/98.21% in LUSC TCGA training cohort; 0.94, 85.92%/97.37 in GEO 66

836; 0.91,89.17%/100% in GEO 83842 smokers; 0.948, 91.67%/100% in GEO83842 non-smokers independent testing cohort. Our study validates SCT, FOXD3, TRIM58 and TAC1 based gene panel has great potential in early recognition of NSCLC undetermined lung nodules. The findings can yield universally accurate

and robust markers facilitating early diagnosis and rapid severity examination.

錨定含吡啶與吡唑雙配位基於氧化鋅奈米粒子的合成、催化與水中的應用

為了解決進擊的巨人 特殊能力的問題，作者廖建勳 這樣論述：

本篇論文選擇以吡唑、吡啶以及含有羧酸根官能基的含氮雜環碳烯為主要結構，藉由中性分子化合物 (NHC-COOH) (5) 錨定在氧化鋅奈米粒子，成功合成出氧化鋅奈米粒子載體 (ZnO-NHC NPs) (9)。而且有機分子修飾在氧化鋅奈米粒子上，能使得氧化鋅奈米粒子載體 (ZnO-NHC NPs) (9) 均勻分散在高極性的溶劑中，因此可以利用核磁共振光譜儀、紅外線光譜儀進行定性與定量分析，並用穿透式電子顯微鏡量測粒徑大小。 除此之外，也把氧化鋅奈米粒子載體 (ZnO-NHC NPs) (9) 與鈀金屬螯合鍵結成鈀金屬氧化鋅奈米粒子載體 (Pd-NHC ZnO NPs) (1

0)。並且應用於 Sonogashira 偶聯反應，探討分子式觸媒 (Pd-NHC) (6) 與載體式觸媒 (Pd-NHC ZnO NPs) (10) 的催化活性。研究結果顯示載體式觸媒 (Pd-NHC ZnO NPs) (10) 的催化效果與分子式觸媒 (Pd-NHC) (6) 相當，這結果可證明不會因為載體化的製程，而減少中心金屬的催化活性，而且載體式觸媒 (Pd-NHC ZnO NPs) (10) 可以藉由簡單的離心、傾析後，即使經過十次回收再利用，仍然保持著很高的催化活性。 工業廢水是近年來熱門討論的議題，廢水中所含有的重金屬離子往往會造成嚴重的環境汙染。而這些有毒的金屬汙染物

不只汙染了大自然，更是影響了人類的健康。因此，如何從廢水中除去重金屬離子是非常重要的技術。在本篇研究中，利用氧化鋅奈米粒子載體 (ZnO-NHC NPs) (9) 當作吸附劑，把廢水中常見的鋅、鉛、鎘等金屬，以及硬水溶液中的鈣、鎂金屬成功吸附。接著利用氫氧化鈉當作脫附劑，成功的把金屬離子脫附下來，並且進行再次吸附，也達到很好的效果。除了吸附與脫附的定性分析，本論文也進行吸附的定量分析實驗，發現與文獻其他相近系統效果相當，尤其在低濃度金屬離子的吸附更是優於許多文獻數值。