Synegistic Anti-proliferation Effects of All -trans Retinoic Acid with Paclitaxel on Autosomal Polycystic Kidney Disease Cell Line

NGUYEN THANH THANH QUE Graduate School Gachon University 2020 국내석사

ABSTRACT Synergistic anti-proliferation effects of all-trans retinoic acid with paclitaxel on autosomal polycystic kidney disease cell line. Que Thanh Thanh Nguyen Supervisor: Prof. Jae Young Kim Department of Life Science Graduate School of Gachon University Autosomal dominant polycystic kidney disease (ADPKD) has been well-known as a monogenic inherited disorder and characterized by cyst development in the kidney. In recent years, the mechanism in autosomal dominant polycystic kidney disease (ADPKD) associated to genetic factors and non-genetic factors have been widely studied to get deep knowledge about ADPKD. In renal tubules, renal epithelial cells over-growth due to lower intracellular calcium level and the mitogenic effect of cAMP (cyclic adenosine monophosphate), is one of the hallmark features that originated cystogenesis. In this study, for the first time, we investigated the synergistic effects of combinatory treatment between all-trans retinoic acid (ATRA), an active form of vitamin A, and paclitaxel, a high effective anticancer drug, on the autosomal dominant polycystic kidney cell line. Cells were treated with a combination of ATRA with paclitaxel for 48 h and then analyzed by cell viability assay. In combinatory treatment groups, our data indicated that the percentage of cell viability was significantly decreased in the comparison with DMSO (control) and ATRA/paclitaxel (alone) treatment. Cell cycle arrest showed that the combinatory treatment of ATRA with paclitaxel induce ADPKD cell line arrest at the G2/M phase. Furthermore, apoptotic cells were detected in our study by Annexin V/PI staining. The up-regulation of p53 protein expression and caspase activation could be involved in apoptosis signal and cell cycle arrest. We revealed that the intra-calcium level was sharply increased by combined treatment of ATRA and paclitaxel after 72 h of treatment and this enhance was blocked by RARα/RXRα antagonist or calcium channel blockers. Besides, ADPKD cell proliferation was controlled through the ERK signaling pathway by in phosphorylated ERK. Our result suggested the function of combinatorial treatment of ATRA with paclitaxel which expresses synergistic anti-proliferation effect on ADPKD cell proliferation by inducing cell cycle arresting, apoptosis and suppressing the ERK signaling pathway. Keywords: Autosomal polycystic kidney disease (ADPKD), ATRA, paclitaxel, cell cycle arrest, apoptosis, intracellular calcium, phosphorylated ERK1/2.

Comparison Analysis of Accessibility Infrastructure for Elderly and Disabled Between South Korea Subway and Jakarta Commuter Railway Station

Aryanti, Riris Aryanti Gachon University Graduate School 2016 국내석사

Accessibility is about giving equal access to everyone and without being able to access facilities and services, a person with disabilities will never be fully included (United Nation, 2007). The friendly environment is the one of human prospect life, accessibility becomes the real fact to create sustainability environment fulfill people mobility needs. Proper access is important to support their availability access, happily and independently life. Most of the public facilities in South Korea and Western countries have provided proper access for elderly and disabled. Unlike Indonesia, accessibility standard has not been applied appropriately. The Aim of this research is highlighting the assesment result of railway station infrastructure by using Rank Weighted Method and SWOT analysis to know the affect factor for create the strategic action plan regarding accessibility railway infrastructure for elderly and disabled. Create the friendly and inclusive environment by give the best infrastructure design standard of Jakarta Commuter Railway public services accessible to their beneficiaries disregarding their physical, mental or language limitations and urging the needs of improving safety awareness and empowering the disabled society eith more access to using rail commuter railway in Jakarta.

Assessment of the PGRN and MAPT mutations in young(<65 years)Korean dementia patients

Lingyan Shen Gachon University Graduate School 2014 국내석사

Frontotemporal dementia (FTD) is the second most common form of early-onset (<65 years of age) neurodegenerative disease after Alzheimer’s disease (AD). At least seven genes have been reported as responsible risk factors for FTD, of which PGRN and MAPT were identified as the main disease-causing genes with 50% of the frequency for FTD, especially for familial FTD. To date, only a few studies of the two genes were performed in Asia, especially in Korea. The aim of this study is to investigate PGRN and MAPT mutations in young Korean dementia patients, and to explore the genetic and clinical features of various neurodegenerative disorders in Korea. PGRN and MAPT were analyzed by direct sequencing for 110 young Korean patients with early onset dementia (89EOAD and 21FTD), followed by single strand conformation polymorphism (SSCP) analyses, web-based splice sites prediction and/or protein function prediction, and in silico prediction and protein modeling. One novel deletion mutation (c.IVS8+23_+26delTGGG), one novel missense mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe), one novel intronic polymorphism (c.IVS12+56G>C), one common mutation which might be novel in Asia/Korea (rs113219200) and four common mutations (rs9897526, rs850713, rs5848 and rs25646; Asp108) were detected in the PGRN gene. But only two known silent mutations (rs115381139; Asn727 and rs11568305; Pro587) were identified in the MAPT gene. In addition, seven new types of co-existed SNPs in the PGRN gene were found in nine patients. Unfortunately, SSCP failed because of the huge size of PCR products. Web-based splice sites predictors showed the novel deletion mutation (c.IVS8+23_+26delTGGG) might cause disturbances in the splicing of PGRN transcript, since it is located near one splice site. Protein function prediction for the functional effect in GRNs (3 isoforms) caused by the novel missense mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe) showed possibly damaging (0.878) or benign (0.176), probably damaging (0.998) or probably damaging (0.933), and probably damaging (0.958) or possibly damaging (0.536) results based on the structures of GRN1, GRN2 and GRN3, respectively. In silico models showed the novel missense mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe) was located in the random coil structure at the C-terminal of GRNs (3 isoforms). Since phenylalanine and leucine are nonpolar and hydrophobic animo acids, random coil structure at the C-ternimal of GRNs (3 isoforms) might be changed by this novel point mutation (c.1767G>T, Leu589Phe; Leu434Phe and/or Leu409Phe). This work provided new insight into study for FTD in Asia.

Optical birefringence induced by surface plasmon resonance in optical fiber with bi-metallic thin film deposition

Nguyen Tan Tai Gachon University Graduate School 2012 국내석사

Surface Plasmon Resonance (SPR) technique with optical fiber technology has enormous advancements in sensing of various physical, chemistry and biochemistry parameter. In this work, we present the optical birefringence properties of the optical fiber cladding that exist as an evanescent field where the refractive index of the analyte solution is applied for optical sensor aspiration. To enhance the performance of the sensor, we have investigated different thickness of TiO2 coating, and bimetallic thin film alloy combinations. In addition, we describe a balanced homodyne detection method for the intensity difference change between the s and p polarization lights in the surface plasmon resonance sensing systems is strongly determined by the refractive index of the test sample. The proposed method can measure very small change of refractive index of glycerol solution, which 4.37x10-8 refractive index units (RIU). This method is a simple optical setup, easily to operate in the real time and low cost. Therefore, due to the experiment set up, our method can also eliminate the surrounding noise. Keywords: Surface Plasmon Resonance, Evanescent wave, Homodyne interferometry, Balanced detector.

Machine Learning Approaches for Cyber Security against Phishing and Poisoning Attacks in Artificial Intelligence Environment

SAMEEN MARIA Gachon University Graduate School 2021 국내석사

Whenever security is concern, cybersecurity is the one that is highlighted and discussed the most. With the ease of access of Internet, cyber threats and attacks are increasing day by day. On one hand, we are getting closer and connected to each other; on the other hand, we are becoming more and more vulnerable to cyber-attacks. To overcome this cyber vulnerability several approaches have applied among which AI is one of them. However, with the passage of time as AI improved cybersecurity, adversaries also began to employ AI for adversarial attacks. Moreover, AI itself is vulnerable against various severe attacks at different phases of its pipeline. Therefore, when AI is deployed or augmented in cyber systems, AI opens various opportunities for adversaries to perform subtle and simple yet severe attacks on cyber systems. These AI-based attacks raised a great security threat to cybersecurity and hence, posed a need for approaches which can address those AI-based cyber-attacks. To study the security impact of AI environment on cybersecurity, we first design an ensemble machine learning-based detection system called PhishHaven to identify AI-generated as well as human-crafted phishing URLs. To the best of our knowledge, this is the first study to consider detecting phishing attacks by both AI and human attackers. PhishHaven employs lexical analysis for feature extraction. To further enhance lexical analysis, we introduce URL HTML Encoding to classify URL on-the-fly and proactively compare with some of the existing methods. We also introduce a URL Hit approach to deal with tiny URLs, which is an open problem yet to be solved. Moreover, the final classification of URLs is made on an unbiased voting mechanism in PhishHaven, which aims to avoid misclassification when the number of votes is equal. To speed up the ensemble-based machine learning models, PhishHaven employs a multi-threading approach to execute the classification in parallel, leading to real-time detection. Theoretical analysis of our solution shows that (1) it can always detect tiny URLs, and (2) it can detect future AI-generated Phishing URLs based on our selected exical features with 100% accuracy. Through experiments, we analyse our solution with a benchmark dataset of 100,000 phishing and normal URLs. The results show that PhishHaven can achieve 98.00% accuracy, outperforming the existing lexical-based human-crafted phishing URLs detection systems. Furthermore, we consider data poisoning attack, a type of attack in which an adversary manipulates the training dataset to degrade the machine learning system’s performance. Data poisoning attacks are challenging to detect, and even more difficult to respond to, particularly in the Internet of Things (IoT) environment. To address this problem, we propose the first proactive data poisoning attack detection framework using distance measures. We found that Jaccard Distance (JD) can be used in the proposed framework (among other distance measures) and we finally improved the JD to attain an Optimized JD (OJD) with lower time and space complexity. Our security analysis shows that the proposed framework is secure against data poisoning attacks by considering key features of adversarial attacks. We conclude that the proposed OJD-based framework is effective and efficient against data poisoning attacks where in-time detection is critical for IoT applications with large volumes of streaming data.

Servant Leadership and Employee Creativity : Moderated Mediation Analysis of Competence, Perceived Organizational Support, and Dyadic Duration

NGUYEN PHAN HANH THAO Gachon University, Graduate School 2018 국내석사

Identifying the precedents of creativity is an important research topic that could help organizations survive under fierce competition. To further contribute to the existing literature of creativity, the author examined the roles of competence, perceived organizational support (POS), and dyadic duration in the relationship between servant leadership and employee creative behavior. The author proposed and tested the moderated mediation model with data from leader-employee dyads collected in a Vietnamese engineering firm. The results showed that employee competence is a significant mediator of the relationship between servant leadership and employee creativity. Furthermore, POS has a moderated mediating role, such that the mediated relationship (i.e., servant leadership, competence, and creativity) is more salient under high POS than under low POS, while the moderated mediating role of dyadic duration was not proven as significant. Theoretical and practical implications are discussed.

Surface chemical modification forplastic microfluidic device fabrication for Lab on a Chip application

Wu Jing Gachon University Graduate School 2014 국내석사

Organic fatty acids production from marine macroalgae and chicken manure by anaerobic fermentation

Guo Lei Gachon University Graduate School 2014 국내석사

The volatile fatty acids (VFAs) are organic acids which are the main product of many bioprocesses. These VFAs have carboxylic groups in their structure which contributes to their acidic nature. In this investigation VFAs from macroalgae (Laminaria japonica, Pachymeniopsis elliptica and Enteromorpha crinita) and a mixture of seaweed with chicken manure (CM) by co-fermentation technique was studied. he main objective of this work was to investigate the production of VFAs from different algae’s and at varying CM ratios. Further, optimization of the co-fermentation process for the pretreated macroalgae and CM based on volatile solids, production was carried out. The maximum VFAs yield of 8.75g/L was achieved for the mixture of Laminaria japonica with chicken manure(ratio of the two substrates was 7:3 on the basis of volatile solid) after a period of 4 days. Similarly for Pachymeniopsis elliptica, and Enteromorpha crinite, the VFAs yield of 5.21g/L and 4.39g/L at seaweed: CM ratios of 7:3 and 4:1 was observed. The study demonstrated that pretreatment of the substrate with alkali solutions was vital for achieving enhanced VFAs production. A VFAs yield of 9.6g/L was resulted pretreatment of seaweed with CM at a ratio of 7:3 (based on volatile solid). Thus the present investigation highlights that co-digestion of macroalgae and CM under different anaerobic digestion conditions improves the efficiency of the fermentation thus increasing theVFAs production.

All-trans retinoic acid-induced Carboxypeptidase D secretion of Human monocytic THP-1

Nguyen Thi Thu Hang Gachon University, Graduate School 2018 국내석사

Carboxypeptidase D (CPD) is a metallocarboxypeptidase, which cleaves C terminal arginine or lysine residue from peptides using a zinc ion in its active site. In this study, we examined the effect of all-trans retinoic acid (ATRA) on CPD expression and secretion of the human monocytic THP-1 cell line. CPD mRNA expression was examined by quantitative real-time PCR. CPD expression was significantly enhanced by various concentrations of ATRA. This enhanced expression was found to depend on RAR/RXR pathway. Since CPD is known to mainly express on cell membrane, cell surface CPD expression was measured by flow cytometry. Despite a significant increase in mRNA expression, cell surface CPD expression was not changed by ATRA treatment. To find reason for mRNA and2 protein expression discrepancy, we measured secreted CPD protein in the culture supernatant by western blot analysis. CPD secretion was significantly enhanced by ATRA treatment in time and concentrationdependent manners. This enhanced CPD secretion was not dependent on RAR/RXR pathway. ATRA-induced CPD secretion was reversed by pre-treatment of dexamethasone, anti-inflammatory drug. To find a candidate substrate of secreted CPD, purified bradykinin, an inflammatory mediator, was subjected to concentrated culture supernatants from ATRA-treated cells, and possible cleavage of bradykinin was measured by HPLC. Bradykinin specific peak was diminished by treatment with concentrated culture supernatants from ATRA-treated cells. This diminished bradykinin peak was partly reversed by dexamethasone treatment. Since desarg9-bradykinin is known to bind bradykinin B1 receptor and to induce inflammatory responses, bradykinin B1 receptor mRNA expression of THP-1 cells was examined. Bradykinin B1 receptor mRNA expression of ATRA treated cells was up-regulated in time and concentration-dependent manners. In conclusion, our results demonstrate that ATRA enhances CPD expression and secretion of human monocytic THP-1 cells, and suggest possible involvement of ATRA-induced secreted CPD in bradykinin cleavage to produce truncated version of bradykinin, another potent inflammatory mediator.

Electrochemical Property and Antibacterial Activity of Polyaniline Coated Gold Nanorods

Liang, Xiaohong Gachon University Graduate School 2016 국내석사

Non-agglomerate and monodispersed gold nanorods (GNRs) were synthesized by seed-mediated method. Polyaniline coated gold nanorods (PANI-GNRs) were synthesized by in situ chemical polymerization method. Analytical and morphological characterizations were revealed by various techniques such as UV-vis spectroscopy, TEM, SEM, and FTIR. The combination of 0.91% of aniline with 5ml of GNRs has provided better electrochemical property at 0.52 V and 1.30 V, respectively. Minimum inhibitory concentration (MIC) of laser irradiated PANI-GNRs, PANI-GNRs, laser irradiated GNRs were investigated, compared to the standard drug kanamycin with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by the micro dilution method. Laser irradiated PANI-GNRs exhibited significant bactericidal property against E. coli and S. aureus. Fluorescence and AFM images support the bacterial death by the prepared nanomaterials to the bacteria’s. The synthesized nanomaterials have good potential in waste water treatment, biomedical and pharmaceutical application.