49 research outputs found
東澳嶺崩塌地之地形演育分析
梅姬颱風 (2010) 與東北季風之共伴效應於台灣宜蘭縣蘇澳地區帶來了豐沛降雨,高累積雨量造成了台9 線蘇花公路群集性土砂災害,尤其在115.9K 上邊坡更誘發了約210 萬m3 之大規模崩塌土砂災害。本文從現地地質調查、致災機制、水文分析及遙測影像判釋等面向進行討論。由降雨-延時-頻率分析得知近年來誘發重大崩塌事件的雨量皆高於200 年回歸週期,並獲致良好判別致災雨場之I-R 圖降雨臨界線關係(Re+53.5Iave=1,146)。多時期遙測影像判釋指出東澳嶺坡頂之弧型張力裂隙仍有持續溯源發展之趨勢。裸露崩塌地不連續面方位密度分布圖之裂隙位態大致與區域地質構造位態 (N70°W) 相近,顯示本區域崩塌主要仍受地質條件主控。此外,蝕溝溯源侵蝕、剪裂帶分布及凹漥坡型亦為影響研究區崩塌地地貌變遷之重要因子,而前期地震或長延時高強度降雨則為外在促崩因子。Typhoon Megi coupled with the northeastern monsoon induced an extreme rainfall of 939 mm on the Suao area, Yilan County, in eastern Taiwan on October 21st, 2010, causing the Dong-Ao Peak landslide of 2.1 million m3 along the coastal Su-Hua Section of Highway Route 9. This study adopts a geological survey, rainfall data, satellite images, orthophotos, and high-resolution DEM based on airborne laser scanner surveys to quantify the morphological changes before and after landslide events following major rainfall events since 2010. Rainfall frequency analysis indicates the cumulative precipitation triggering landslide events is greater than the 200-year return period. In addition, both the entrainment effect of debris flow and toe erosion on the down-slope is shown to induce regressive sliding failure at the adjacent roadbed. The results suggest that geological factors such as head-cutting erosion and the concave landform shape the landform evolution of the catchment. The occurrence of landslides also depends on antecedent earthquake events and extreme intense rainfalls
Hepatocellular Nuclear Factor 4 alpha (HNF-4 alpha) activation by saRNA rescues dyslipidemia and promotes favorable metabolic profile in a high fat diet (HFD) fed rat model.
The Bi-Functional RNA Aptamers Inhibit Pancreatic Ductal Adenocarcinoma (PDAC) Growth In Vivo
Systemic administration of a novel development candidate, MTL-CEBPA, up-regulates the liver-enriched transcription factor C/EBP-alpha and reverses CCl4-induced liver failure in vivo.
A Novel RNA Oligonucleotide Improves Liver Function and Inhibits Liver Carcinogenesis In Vivo
Hepatocellular carcinoma (HCC) occurs predominantly in patients with liver cirrhosis. Here we show an innovative RNA-based targeted approach to enhance endogenous albumin production while reducing liver tumor burden. We designed short-activating RNAs (saRNA) to enhance expression of C/EBP (CCAAT/enhancer-binding protein-), a transcriptional regulator and activator of albumin gene expression. Increased levels of both C/EBP and albumin mRNA in addition to a 3-fold increase in albumin secretion and 50% decrease in cell proliferation was observed in C/EBP-saRNA transfected HepG2 cells. Intravenous injection of C/EBP-saRNA in a cirrhotic rat model with multifocal liver tumors increased circulating serum albumin by over 30%, showing evidence of improved liver function. Tumor burden decreased by 80% (P = 0.003) with a 40% reduction in a marker of preneoplastic transformation. Since C/EBP has known antiproliferative activities by way of retinoblastoma, p21, and cyclins, we used messenger RNA (mRNA) expression liver cancer-specific microarray in C/EBP-saRNA-transfected HepG2 cells to confirm down-regulation of genes strongly enriched for negative regulation of apoptosis, angiogenesis, and metastasis. Up-regulated genes were enriched for tumor suppressors and positive regulators of cell differentiation. A quantitative polymerase chain reaction (PCR) and western blot analysis of C/EBP-saRNA-transfected cells suggested that in addition to the known antiproliferative targets of C/EBP, we also observed suppression of interleukin (IL)6R, c-Myc, and reduced STAT3 phosphorylation. Conclusion: A novel injectable saRNA-oligonucleotide that enhances C/EBP expression successfully reduces tumor burden and simultaneously improves liver function in a clinically relevant liver cirrhosis/HCC model. (Hepatology 2014;58:216-227
Targeted Delivery of C/EBP alpha -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo
The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence of PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method of delivering antitumorigenic therapy in PDAC by upregulating the transcriptional factor CCAAT/enhancer-binding protein-a (C/EBP alpha), recognized for its antiproliferative effects. Small activating RNA (saRNA) duplexes designed to increase C/EBP alpha expression were linked onto PDAC-specific 2'-Fluropyrimidine RNA aptamers (2'F-RNA) - P19 and P1 for construction of a cell type-specific delivery vehicle. Both P19- and P1-C/EBP alpha-saRNA conjugates increased expression of C/EBP alpha and significantly suppressed cell proliferation. Tail vein injection of the saRNA/aptamer conjugates in PANC-1 and in gemcitabine-resistant AsPC-1 mouse-xenografts led to reduced tumor size with no observed toxicity. To exploit the specificity of the P19/P1 aptamers for PDAC cells, we also assessed if conjugation with Cy3 would allow it to be used as a diagnostic tool on archival human pancreatic duodenectomy tissue sections. Scoring pattern from 72 patients suggested a positive correlation between high fluorescent signal in the high mortality patient groups. We propose a novel aptamer-based strategy for delivery of targeted molecular therapy in advanced PDAC where current modalities fail
Targeted Delivery of C/EBP alpha-Small Activation RNA (saRNA) by RNA Aptamer Inhibits the Growth of Pancreatic Ductal Adenocarcinoma (PDAC) In Vivo
Development of antibody functionalized magnetic nanoparticles for the immunoassay of carcinoembryonic antigen: a feasibility study for clinical use
Background: Magnetic nanoparticles functionalized antibodies are used for in-vitro assays on bio-markers. This work demonstrates the synthesis of high-quality magnetic nanoparticles coated with antibodies against carcinoembryonic antigen (CEA). Various characterizations, such as particle size, particle suspension, bio-activity and the stability of bio-magnetic nanoparticles suspended in liquid, are studied. The properties for the assay of CEA molecules in serum are also studied. The assay method used is so-called immunomagnetic reduction. ;Results: The results show that the effects of common materials in serum that interfere with detected signals are not significant. The low-detection limit is 0.21 ng/ml, which is well below the clinical threshold of 2.5 ng/ml. ;Conclusions: The dynamic range for the assay of CEA molecules in serum is 500 ng/ml. By assaying serum CEA molecules from 24 normal controls and 30 colorectal-cancer patients, the threshold for the serum-CEA concentration to diagnose colorectal cancer is 4.05 ng/ml, which results in a clinical sensitivity of 0.90 and specificity of 0.87