Evaluation of the phage display protocol for target identification of small molecules

Currently, the phage display is the potential method for target identification of small molecules. Thus, the first objective of this thesis was to establish a cDNA phage display protocol for affinity isolation of target proteins binding to small molecules of interest as an alternative to the affinity-based approach. For that reason we generated a cDNA phage display library using HeLa cells, which are usually used for phenotypic studies and for target identification using affinity chromatography in our group. This approach was applied different molecules including melophlin A, CD 267, tubulexin A. and glutathione (GSH) as control. Preincubation the library with streptavidin-biotin or streptavidin-PEG-biotin or inactive compound before biopanning step was employed to reduce on-specific binding. In parallel, specific elution approaches was employed to elute proteins and identified one known hit of GSH. The binders identified by phage display were not identical with the binders identified using affinity purification in the case of melophlin A, CD 267 and tubulexin A. Even though we could succeed in establishing a protocol with the optimal conditions determined. However, there is unlikely to get the same hits of affinity purification for melophlin A, CD 267 and tubulexin A. A separate study focused on the biological evaluation of hit compounds from phenotypic high content screening that monitors changes in cytoskeleton and DNA. Molecules interfering with microtubule dynamics are among the most successful therapeutics for the treatment of cancer. Despite the availability of many tubulin targeting agents, cells can become resistant towards the drugs. Hence, there is high demand for the identification of new anti-tubulin agents that are able to overcome anti-tubulin drug resistance. Within this work, the aim was to further validate the effects of tubulexin A and podoverin A and characterize their mode of action. Tubulexin A and the natural product podoverin A are potent inducers of a G2/M cell cycle arrest and apoptosis. Tubulexin A is the most active compound identified from tetrahydropyran library. Base on target validation showed that tubulexin A inhibits tubulin polymerization by targeting the vinca alkaloid binding site of tubulin and also bind to the protein CAS. Further validation of the effects of those compounds on tubulin polymerization, the cell cycle, and their binding to CAS was done by biophysical measurements, binding assays, tubulin polymerization assays, immunofluorescence and life time imaging, binding assays, and affinity chromatographic methods. Results showed that CAS binds to tubulexin A independent from tubulin. Additionally, tubulin polymerization is inhibited in a synergistic manner in the presence of both, tubulexin A and CAS in vitro. Based on results of overcome vinblastine-resistance, tubulexin A can become a promising antimitotic drug for cancer treatment with the dual mode of action of the tubulexin A and CAS. For the natural product podoverin A is the most active mitosis modulator in natural product library. This compound is a potential target for further study on natural product as mitosis modulator to use for anticancer drugs, also used as natural product scaffold for synthesis library. The third aim of this thesis is discovery new CAS inhibitors as mitosis modulators. Despite the high relevance of CAS as a target in cancer, there is no small molecule targeting CAS published yet. Therefore, additional focus of this work was to discover further compounds that bind to CAS which might interfere with CAS function and thus might inhibit growth of cancer cells. A reverse chemical genomics-approach was chosen in collaboration with the group of Prof. Osada (RIKEN-Wako-Japan). This strategy is based on a chemical array screening. After chemical array screening of approximately 25,000 compounds, 263 potential hit compounds have been obtained. Further validation the hit compounds was based on phenotypic changes and specific function of the target using immunofluorescence and life time imaging, biophysical methods for the determination of the binding affinity, as well as studies on the interaction of the hit compounds with DNA and tubulin polymerization in vitro. The most interesting compound R89 was further validated on HeLa cells and we found that this compound inhibited cell proliferation. Result showed that R89 has effect on mitosis by formation of multipolar mitotic spindles and caused chromosome congression defects and also induces nuclear accumulation of RANBP1. Thus R89 is an interesting mitosis modulator to study for anticancer drugs

L’effet de l’annonce médiatique d’irrégularités financières sur les risques financiers des entreprises

Les irrégularités financières en entreprise ne sont pas un nouveau phénomène. Cependant, depuis les années 90 avec l’omniprésence des médias, la diffusion médiatique des annonces de fraudes boursières semble avoir un impact significatif sur le comportement des investisseurs et, plus particulièrement, sur les cours boursiers. Toutefois, au-delà de son effet sur la performance financière, une autre question fondamentale se pose : est-ce que l’annonce médiatique d’irrégularités ou de fraudes financières influence le risque des entreprises ? Si oui, quels sont les types de risque affectés et quel est l’effet du traitement médiatique ? Afin de répondre à cette question, ce papier se base sur un modèle d’évaluation d’actif conditionnel et sur un modèle de variance conditionnelle GJR-GARCH. Ces modèles capturent, respectivement, la variation du risque systématique et la variation du risque total. Nous étudions ces variations de risque selon le traitement médiatique, le type de fraude, la victime de fraude ainsi que la décision juridique. Notre échantillon contient 491 événements-entreprise, concernant des fraudes et des irrégularités financières d’une entreprise (première diffusion et suivi) qui commence, au plus tôt, le 1er janvier 2000, et qui se termine, au plus tard, le 31 décembre 2011. En général, nos résultats ne permettent pas de conclure à une augmentation significative du risque d’une entreprise suite à une annonce d’irrégularité. Ces résultats sont cohérents avec la littérature existante sur l’analyse de risque à la suite d’une annonce de fraude. Plusieurs avenues sont proposées pour expliquer cette conclusion qui peut sembler, de prime abord, contre-intuitive. Ainsi, cette conclusion pourrait être expliquée par l’anticipation de l’annonce d’une irrégularité par les investisseurs, par une meilleure gestion anticipée de l’entreprise suite à la révélation d’une irrégularité, ou encore par la neutralité de l’irrégularité sur le risque de l’entreprise. Nos résultats indiquent cependant des augmentations significatives de risque pour des entreprises touchées par des fraudes « corporatives », par du piratage ou par une fraude contre le gouvernement. Ces résultats sont robustes pour différents horizons d’estimation et pour différents sous-échantillons

ENGLISH-MAJORED STUDENTS’ LISTENING DIFFICULTIES AND USE OF STRATEGIES AT MIEN DONG UNIVERSITY OF TECHNOLOGY, VIETNAM

Through the years, difficulties in English listening and listening strategies have been conducted by many researchers. Most of studies have pointed out the common difficulties and strategies which students often have. Focusing on the same subject with a new perspective, this research aimed at understanding English majors’ difficulties in listening and use of listening strategies. A total of ninety eight freshmen English-majored students at Mien Dong University took part in answering the questionnaire and five students answered the semi-structure interview questions. The data gained from the questionnaire were analyzed by SPSS version 20.0 in terms of descriptive statistic. The findings revealed that English-majored students had many difficulties in listening such as the difficulties related to the listener, the content of the dialogue, the speaker, the physical setting and the linguistic factors. In terms of listening strategies, the finding showed that the cognitive listening strategies were used more frequently than metacognitive and socio-affective strategies. Based on the findings, some implications were made to contribute to the administrations, teachers and students at Mien Dong University of Technology.  Article visualizations

Strengthen roles of commercial banks in vietnam economy– a case of eximbank

Is it the time for us to evaluate roles of Vietnam commercial banks and importance of risk management activities? This paper uses both quantitative analysis with statistical data and charts, combined with qualitative analysis including synthesis, inductive and explanatory methods in order to estimate and compare market risk via beta CAPM of Eximbank (EIB) and Asia Commercial Bank (ACB), 2 big listed joint stock banks in Vietnam. Research findings show us that market risk of Eximbank is higher and increase during post-low (L) inflation stage, compared to pre-L inflation time. Results may be used for policy implications and research models can be references for other countries including emerging markets

Determination of the content of major chemical components and bioactive compounds and antioxidant ability of Hong Quan (Flacourtia jangomas (Lour.) Raeusch) fruit cultivated in An Giang, Vietnam

Hong Quan (Flacourtia jangomas (Lour.) Raeusch) is a new fruit that has appeared recently and it is cultivated with other orchards or under forest canopy of Tri Ton and Tinh Bien district at An Giang province. Since this fruit has not been popularized in Vietnam, there is a shortage in research about chemical compositions of Hong Quan. Therefore, quantitative analysis of main chemical components, bioactive compounds and antioxidant activity of this kind of fruit need to be carried out to enhance its applications in food. Results showed that Hong Quan fruits contain 76.50% ± 2.56 of moisture, carbohydrate is 24.86% ± 1.54, protein is 9.19% ± 0.49, lipid is 0.68% ± 0.21, total sugar is 10,91% ± 0.88, ash is 1.05% ± 0.08, fiber is 8.39% ± 0.95 and vitamin C is 81.62 ± 3.99 mg/100g. The content of bioactive compounds such as carotenoids, phenolics, tannins, alkaloids, saponins and flavonoids were 9.87 ± 0.40 mg/100g, 456.32 ± 23.81 mgGAE/100g, 944.08 ± 26.31 mgTAE/100g, 586.68 ± 44.56 mgCE/100g, 20.87 ± 2.00 mgSE/100g and 65.95 ± 2.92 mgQE/100g fresh weight respectively. Moreover, antioxidant capacity of extract ethanol from fruit was high level as the free radical scavenging ability (DPPH) at 88.65% ± 1.23, the ability to reduce iron (FRAP) at 15.24 ± 0.26 mM FeSO4/100g and the antioxidant ability index (AAI) at 8.13 ± 0.82. Hong Quan fruit promisingly could be a good source of commercial processing products or cosmetic due to high level of nutrients and functional compounds

INVESTIGATION OF THE ANTIBIOTIC RESISTANCE: THE CASE OF BUU DIEN GENERAL HOSPITAL IN HO CHI MINH CITY

Objective: In Vietnam, antibiotic resistance has been gained the attention of medical professionals in antibiotic use management. This study aimed to investigate the antibiotic resistance among hospital-acquired infections at Buu Dien General Hospital in Ho Chi Minh City in the period of 01-12/2017. Methods: This cross-sectional descriptive study was conducted on the retrospective data of all antibiograms of bacteria isolated from hospital-acquired infections at Buu Dien General Hospital in Ho Chi Minh City in the period of 01-12/2017 to investigate the antibiotic resistance. Characteristics of antibiotic resistance were described by frequency and percentage of types of bacteria isolated and antibiotics being resistant. Results: A total of 179 isolates were collected during the period 01-12/2017, of which E. coli was the most commonly isolated pathogen (41.3%). The highest prevalent infections were in the skin and mucosa; respiratory tract; and urinary tract (34.6%; 32.4%; and 27.9%). The antibiotic susceptibility testing used 21 types of antibiotics. Among them, S. aureus was 82% resistant to clindamycin and 75% resistant to cefuroxime; the Proteus resistance percentages to amoxicillin/clavulanic, second-generation cephalosporins, ciprofloxacin and fosfomycin varied from 50 to 93%; Pseudomonas was 92% resistant to fosfomycin and 62% resistant to ceftazidime; A. baumannii was resistant to most classes of agents used (50-75%). Both E. coli and Klebsiella were highly resistant to gentamicin, amoxicillin, ciprofloxacin, 2nd and 3rd generation cephalosporin’s. Polymyxin B-resistant Proteus cultures were detected at 67%. Conclusion: The study described the antibiotic resistance situation of hospital-acquired bacteria at the Buu Dien General Hospital from 01-12/2017. This information will aid physicians to select proper antibiotics for their patients in the next period

IDENTIFICATION AND CHARACTERIZATION OF A PURPLE NONSULFUR BACTERIUM ISOLATED FROM COASTAL AREA OF HAI PHONG FOR USING IN PRODUCTION OF UNSATURATED FATTY ACID (OMEGA 6, 7, 9)

Purple nonsulfur bacteria are a group that has so much biotechnological applications, particularly in producing of functional food rich with unsaturated fatty acids. A purple nonsulfur bacterium (named HPB.6) was chosen based on its strong growth, high lipid and synthesis of unsaturated fatty acid (omega 6,7,9). Studying on basic biological characteristics showed that the cells of HPB.6 were observed as ovoid-rod shape, none motility, Gram negative staining. The diameter of single bacterium was about 0.8-1.0 µm. The cells divide by binary fission and had bacteriochlorophyll a (Bchl a). This bacterium grew well on medium with carbon and nitrogen sources such as acetate, succinate, pyruvate, butyrate, glutamate, arginine, leucine, tyrosine, alanine, methionine, threonine, glutamine, yeast extract and NH4Cl. This selected strain grew well on medium with salt concentrations from 1.5 - 6.0% (optimum 3%), pH from 5.0 to 8.0 (optimum at pH 6.5) and could withstand Na2S at 4.0 - 5.2 mM. Based on morphological, physiological properties and 16S rRNA analysis received demonstrated that HPB.6 strain belongs to the species Rhodovulum sulfidophilum

COMPARATIVE STUDY ON VOLATILE COMPOUNDS OF AGARWOOD FROM KHANH HOA PROVINCE EXTRACTED BY DIFFERENT METHODS

Agarwood from Aquilaria crassna cultivated in Khanh Hoa province was extracted by 5 methods, including simple, enzyme-assited, and microwave-assisted hydrodistillation, extraction with solvent and supercritical carbon dioxide. The volatile compounds of the products were analyzed by GC-MS. Almost all samples contain some common characteristic components, such as Valerianol, Agarospirol, Eudesmol b-, Eudesmol 10-epi-g-, 2-Allyl-4-methylphenol, Guaiol and Neopetasone. However, there were obvious differences in yields, composition, and number of identified components. The application of the more advanced methods for the extraction of agarwood resulted in saving of time and energy, and some improvement of product yield. However, these methods also lead to unconventional products with many unknown components, what requires further investigations

The impact of government support on firm performance in Vietnam. New evidence from a dynamic approach

Using a sample of private manufacturing small- and medium-sized enterprises (SMEs) in the period 2007\u20132015, this paper examines the effect of government support on firms\u2019 financial performance in Vietnam. Contrary to many previous studies, the study finds that government assistance affects firms\u2019 financial performance after controlling for heterogeneity, unobservable factors, and dynamic endogeneity. The finding supports the viewpoint of institutional theory. The study also reveals that assistance measures, such as tax exemptions, soft loans, and investment incentives to promote financial performance, are vital for the development of Vietnamese private SMEs