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

為了解決P jj56 veg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.

雙重犯罪原則之理論與實務─以洗錢防制之國際刑事司法互助及刑罰域外效力為中心

為了解決P jj56 veg的問題，作者黃謀信 這樣論述：

本文共分為六章，除第一章「前言」及第六章「結論及建議」外，主要部分共4章。第二章先就「雙重犯罪原則之定性」定義「雙重犯罪原則」之意義及理論基礎，本文所指之「雙重犯罪原則」，除傳統之「雙重犯罪原則」概念，指「國際刑事司法互助」方面之「雙重犯罪原則」外，另亦包括「刑罰域外效力」方面之「雙重犯罪原則」。從「雙重犯罪原則」在此兩方面之共同理論性基礎及在法律域外效力控制之差異性，探究為何「雙重犯罪原則」在諸多批評及利益衝突之國際趨勢下，迄今依舊存在，並不會完全消失之理由。第三章探討「雙重犯罪原則之適用趨勢與規範模式」，從相關之「40項建議」、國際公約及刑事司法互助協定對於「雙重犯罪原則」之規範內容進行

比較分析，固然可確立該等國際規範對「雙重犯罪原則」係採取緩解或摒棄適用之國際趨勢。惟具體落實在各國之內國法時，各國基本上仍在「雙重犯罪原則」之前提下，僅進行緩解適用「雙重犯罪原則」。此種與國際趨勢歧異之基本立場，導致國際公約、條約、司法互助協定及各國內國法就「雙重犯罪原則」之規範模式極為分歧，而我國亦不例外，此章乃就相關之「雙重犯罪原則」所採取之具體規範模式及法規適用情形進行比較分析。第四章探討「洗錢防制關於刑事司法互助之雙重犯罪原則」，論述與洗錢防制相關之刑事司法互助及「雙重犯罪原則」之法律規範體系及內容。其中我國新制定之國際刑事司法互助法及因應第三輪APG相互評鑑而大幅修正之洗錢防制法有關

「雙重犯罪原則」之規範內容，代表我國對「雙重犯罪原則」之基本立場，本章乃進而探討我國有關「雙重犯罪原則」所持之基本立場、法規範衝突及具體適用情形。第五章探究「洗錢罪關於域外效力之雙重犯罪原則」，隨著本國刑罰域外效力不斷擴張的結果，國際間及我國對於刑罰域外效力之「雙重犯罪原則」如何回應此種發展趨勢。關於洗錢罪之刑罰域外效力，國際間及我國對於洗錢罪及其前置犯罪之刑罰域外效力，是否均應該採取摒棄或緩解適用「雙重犯罪原則」之立場；我國該如何面對防制洗錢之強勢國際組織FATF及APG等組織，以及該等組織以強勢手段推行之統一標準「 40項建議」等規範及其評鑑結果；因應該等國際強勢組織與規範，探究我國未來有

關「雙重犯罪原則」之修法方向及「雙重犯罪原則」之存廢問題。