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      • Systematics and molecular phylogeny of Cylindrolebrididae (Ostracoda, Myodocopa) from East Asia

        Pham, Huyen Thi Minh 한양대학교 대학원 2022 국내박사

        RANK : 247391

        While extensive studies have been conducted worldwide on the Cylindroleberididae, they still remain classified as unexplored taxa in East Asia. Compared to the total of 229 species belonging to 33 genera recorded worldwide, only a small fraction of that (26 species) has been recorded from East Asia and none from Korea. For this Ph.D. thesis, 22 sampling sites from South Korean and Japanese waters were surveyed as a part of the national project “Discovery of Korean Indigenous Species”, Japanese Association for Marine Biology (JAMBIO) projects, and the training and research vessel (TRV) Toyoshio-maru (Hiroshima University). As a result, collected cylindroleberids were examined and identified to genus and/or species level. A total of 22 cylindroleberid species belonging to 2 subfamilies, 11 genera were recorded. One new genus, Toyoshioleberis Pham, Jöst, and Karanovic, 2021, four new Parasterope Kornicker, 1975 species, three new Xenoleberis Kornicker, 1994 species are described. In addition, I re-describe Xenoleberis yamadai Hiruta, 1979 previously unrecorded from South Korea. An identification key to all representatives of Xenoleberis and the East and Southeast Asian Parasterope are provided. A total of 859 sequences belonging to 228 Myodocopa species have been used for the calculations of the genetic distances. As a result, an overview of the intrageneric and intrafamily DNA distances of two mitochondrial markers (16S rRNA and mtCOI) and three nuclear markers (18S rRNA, 28S rRNA, and internal transcribed spacer - ITS) is provided. A concatenated alignment of 16S and 18S of all available cylindroleberid sequences is used to reconstruct a phylogenetic tree with the aim to assess the position of the new taxa within the family and resolve the currently polyphyletic nature of some cylindroleberid systematic units. Cylindroleberididae 과에 대한 연구는 전 세계에서 광범위하게 수행되었지만 동아시아와 한국에서는 부족한 상황이다. 현재까지 전 세계적으로 보고된 종은 33 속 229 종이고, 동아시아에서 보고한 종은 25 종이다. 국내에서 보고된 종은 아직 없었다. 본 학위논문을 준비하기 위해 국책과제인 “자생생물 조사∙발굴 연구 무척추동물분야”, 일본해양생물학회(JAMBIO) 사업, 연구선(TRV) Toyoshio-maru (Hiroshima University)에서 2014 년부터 한일수역 총 22 개 장소에서 조사를 하였거나, 시료를 제공받았다. 확보한 cylindroleberids 를 분석한 결과 총 2 아과 11 속 22 종으로 구분하였으며, 신속, 신종 미기록종을 보고하였다: 신속 Toyoshioleberis Pham, Jöst, and Karanovic, 2021; Parasterope Kornicker, 1975 에 속하는 4 신종, Xenoleberis Kornicker, 1994 에 포함되는 3 신종. 그리고 Cylindroleberidinae 아과에 속하는 미기록종인 Xenoleberis yamadai Hiruta, 1979 를 고해상도 삽화와 함께 재기재 하였다. 게다가, 동아시아 남아시아에 서식하는 Xenoleberis 와 Parasterope 의 동정 분류키를 함께 제공하였다. 근병아강에(Myodocopa) 속하는 228 종의 총 859 개의 염기서열을 유전적 거리 계산에 사용하였다. 그 결과 2 개의 미토콘드리아 마커(16S rRNA 및 mtCOI)와 3 개의 핵 영역 마커(18S, 28S rRNA, 내부 전사된 Spacer - ITS)의 속(genus), 과(family) 내의 DNA 거리에 대한 개요를 제공하였다. 그리고, 사용 가능한 모든 cylindroleberids 의 16S, 18S 정렬된 염기서열을 이용 분자계통수를 재구성하여 과내 새로운 분류군의 위치를 평가하고 일부 cylindroleberids 의 다계통 특성을 해결하였다.

      • Enavogliflozin, an SGLT2 inhibitor, Improves Nonalcoholic Steatohepatitis Induced by High-Fat High-Cholesterol Diet

        Pham Thi Minh Phuc 강원대학교 대학원 2024 국내석사

        RANK : 247375

        Background: Non-alcoholic fatty liver disease (NAFLD), which is a progressive disease caused by a build-up of fat in the liver, onsets with simple steatosis and potentially advances to non-alcoholic steatohepatitis (NASH) in the presence of inflammation and fibrosis, severely leading to cirrhosis or hepatocellular carcinoma. There is increasing cumulative evidence indicating that sodium-glucose cotransport 2 (SGLT2) inhibitor agents efficaciously alleviate NASH in a mouse model, but there is lack of research mentioning the effect of enavogliflozin on liver disease. Consequently, in this present study, I investigated the impact of this sodium-glucose cotransport 2 inhibitor on high-fat high-cholesterol (HFHC)-diet induced NASH mice. Methods: Male C57BL/6 mice were fed a normal chow diet (CD), HFHC diet, or HFHC diet with enavogliflozin for 12 weeks. Enavogliflozin was administered at a dose of 1.28 mg/kg/day in these experiments. In vitro, LX-2 cells and HepG2 cells were treated with enavogliflozin and different pathological factors. Results: HFHC induced excessive hepatic lipid accumulation, immune cell infiltration, and severe fibrosis. Enavogliflozin administration not only ameliorated hepatic steatosis and fibrotic condition but also suppressed the production of inflammatory cytokines (IL-6, IL-1β). Similar outcomes were observed in in vitro experiments, where enavogliflozin not only hindered the activation of hepatic stellate cells but also mitigated lipid accumulation in hepatocytes. The potential pathway through which enavogliflozin attenuated liver fibrosis development may be associated with the TGF- β1/Smad signaling pathway. Conclusion: My results suggest that enavogliflozin shows efficacy in a mouse model of NASH by attenuating hepatic steatosis, suppressing inflammation, and improving liver fibrosis. Keywords: Enavogliflozin; HFHC diet; Hepatic Stellate Cells; HepG2 cells; Liver Fibrosis; NAFLD; NASH

      • Regulatory Risk Management System for Vietnamese Life Insurance Companies

        Pham Thi Ngoc Lan 숭실대학교 대학원 2017 국내석사

        RANK : 247375

        Regulatory risk management system is a major concern of not only regulators but also of insurers. A regulatory risk management system that is reasonable and that could quantify the risk of insurance companies adequately is basis for sound development of life insurance industry. It will contribute to the sustainability of insurance industry and it provides information important for decision making of insurance companies as well as regulators. This thesis reviews current regulatory risk management system for life insurance companies in Vietnam to identify problems and limitations of it. For that purpose evaluated results for three life insurance companies based on current Vietnamese system and Korean RBC system are compared. Ways to improve current Vietnamese system and a roadmap for future development of the system are suggested. 리스크관리 규제 시스템은 감독당국뿐만 아니라 보험사들의 주요 관심사이다. 리스크에 대한 적정한 평가 결과를 제공하는 합리적인 리스크관리 시스템은 생명보험 산업의 건전한 발전을 위한 기초이다. 적절한 리스크관리 시스템은 보험산업의 지속가능성 측면에 기여할 뿐만 아니라 감독당국과 보험사의 주요 의사결정을 위한 정보를 제공한다. 본 논문에서는 베트남의 현행 리스크관리 규제 시스템에 대해 검토하였다. 현행 시스템의 한계와 문제점을 파악하기 위한 목적이다. 이러한 목적을 위해 베트남에서 사업을 영위하고 있는 세 개 생명보험사들에 대해 베트남의 현행 리스크관리 규제 시스템과 한국의 RBC 시스템을 적용한 결과를 비교, 평가하였다. 또한, 본 논문에서는 베트남의 현행 리스크관리 규제 시스템을 개선하는 방안과 바람직한 앞으로의 개선 일정을 제시하였다.

      • Balancing and Transferring Controls of the Ridable Ballbot

        PHAM DINH BA Kyung Hee University - Graduate School 2018 국내박사

        RANK : 247375

        This thesis focuses on the design and implementation of a ridable ballbot and application of control methodology to control the ridable ballbot. The control methods, which include linear double-loop control and the nonlinear control techniques, such as partial feedback linearization (PFL) and sliding mode control (SMC), are designed based on two versions of the mathematical models of the ridable ballbot system: one describes the two-dimensional (2D) motions of ridable ballbot and the other is extended for its two and half-dimensional (2.5D) motions. The performance and effectiveness of the proposed control methods and accuracy of the mathematical models are demonstrated by both simulation and experiment. The simulation is realized in the PC using Simulink Matlab. The real ridable ballbot is installed for experiment with Visual Studio C++. Generally, a ridable ballbot has a body that balances on top of a ball and forms an underactuated system. The robot has more degrees of freedom (DOF) than independent control inputs. The ridable ballbot accelerates by leaning, but cannot directly control its tilt angles. The body is kept upright at approximately its unstable equilibrium point by only maneuvering the ball, similar to controlling an inverted pendulum. The controllers are first designed for the planar ridable ballbot then improved for the spatial motion of ridable ballbot system. The proposed control scheme concurrently implements three main tasks: balancing, transferring, and rotating a ridable ballbot on the floor. Based on the application of multi-loop control, linear quadratic regulator (LQR), PFL, and SMC techniques, this study proposes one linear optimal double-loop controller and six types of nonlinear controllers represented as follows. (i) Linear double-loop control system with LQR outer-loop and proportional-integral(PI)-plus-feedforward inner-loop controllers. This study proposes a linear double-loop control system based on planar ridable ballbot models. These planar models are linearized around an equilibrium point where the ridable ballbot is in an upright position and stationary. The double-loop control system includes two controllers: one is a PI-plus-feedforward inner-loop controller and the other is an LQR outer-loop controller. The double-loop control system allows the ridable ballbot to overcome the hindrance caused by its heavy weight and bulk and eliminate most of the uncertainties of system parameters, modeling, friction and external disturbances. (ii) The PFL based controller for planar ridable ballbot motion and its extended version for spatial motion. The PFL controller is designed to control balancing and transferring of the ridable ballbot. The planar dynamics of the ridable ballbot is formulated with highly nonlinear second order differential equations. This planar dynamics involves the ball state and body state driven by only one torque input. First, its system dynamics should be divided into ball subsystem model and body subsystem model. Next, two PFL laws are proposed; one is determined by the ball subsystem and the remaining law is got from the feedback linearization of the body subsystem. Considering the body state as the primary system output, the PFL control input is proposed to balance and track the position of the ball to the desired reference trajectory. Because this nonlinear control law does not guarantee the convergence of the overall state variables, the structure of the controller should be modified to satisfy the stability condition of the full state variables. The modification is a linear combination of two components: one is received from feedback linearization of the ball dynamics and body dynamics. Then the proposed controller asymptotically pulls all system responses to the desired values. Improving the aforementioned proposed controller for the spatial ridable ballbot motion, another nonlinear controller is considered for the robot in the case of the most complicated tasks in which the ball, three omnidirectional wheels, and body motions are simultaneously operated. The control structure is designed based on the nonlinear feedback of the ball and body states. First, system dynamics of ridable ballbot composed of four highly nonlinear second-order differential equations are created. Because the ridable ballbot is a second-order underactuated system with non-holonomic velocity constraints and input coupling case, its system dynamics should be separated into ball and body subsystems. Next, the two sub-systems are linearized by using the nonlinear feedback technique. Afterward, considering states as system outputs, a nonlinear controller of the ball subsystem is proposed to track output positions of the ball on the floor to the desired path while another nonlinear controller of the body subsystem is proposed to keep the body at the vertical position. The stability analysis of the two subsystems and the overall system is given to prove the convergence of the system states. Finally, the performance of the proposed nonlinear control method is simulated and experimentally tested for self-balancing and station-keeping, transferring, and robustness against external disturbances. (iii) The hierarchical SMC based controller for the planar motion of the ridable ballbot and its extended version for the spatial motion. SMC is a robust technique applied widely in nonlinear systems to implement and insensitive with external disturbances and uncertainties of system parameters, friction, and modeling. It is especially suitable for underactuated systems, such as ballbot system. The goal of SMC approach is to determine an asymptotically stable surface so that all state trajectories are attracted to this surface and slide along until reaching their desired values. As mentioned, the ridable ballbot is an underactuated system containing uncertain components, such as system parameters, friction factors, and model. Therefore, SMC technique is a proper selection in this study. Two hierarchical SMC schemes are discussed. One is for the planar motion of the ridable ballbot system and the other is improved for the spatial ridable ballbot system. Based on this physical structure, the hierarchical structure of the sliding mode surfaces (SMS) is designed as follows. At first, the SMS of every subsystem is defined. Then the SMS of one subsystem is defined as the first layer SMS. The first layer SMS is used to construct the second layer SMS with the SMSs of another subsystem. This process continues till the SMSs of the entire subsystems are included. According to the hierarchical structure, the total control law is deduced by the Lyapunov theorem. In theory, the asymptotic stability of the entire system of SMSs is proven and the parameter boundaries of the subsystem SMSs are given. (iv) PFL and SMC combination based control scheme for the planar and spatial motion of the ridable ballbot. An improved nonlinear control scheme for the planar motion of the ridable ballbot is proposed applying a combination of two nonlinear control techniques. The first step in combined control design is to decompose the ridable ballbot system into ball and body subsystems. Next, using the PFL technique, the body subsystem control is constructed to control balancing of the robot. The ball transferring control is designed based on the SMC technique and ball subsystem. In the final step, the balancing and transferring control laws are merged to stabilize overall state variables of the ridable ballbot system. Improving the aforementioned controller for the spatial motion of the ridable ballbot, the control scheme is divided into two parts in which each of them implements a particular duty. PFL controls the balance of the body while SMC controls the position of the ball on the floor. A combined nonlinear controller is proposed by integrating PFL based scheme into SMC based structure.

      • 이온성 액체의 생분해성과 생태 독성효과

        Pham Thi Phuong Thuy 전북대학교 대학원 2007 국내석사

        RANK : 247375

        이온성 액체는 휘발성 유기용매를 대체할 수 있는 청정용매로, 여러 공정에 이용할 수 있는 액체상태의 소금이다. 이온성 액체는 구조를 변화시키거나 양이온과 음이온의 구성을 바꿈으로써 산업공정의 사용에 적합하도록 화학적, 물리학적 특성을 변화 시킬 수 있다. 이렇게 합성된 이온성 액체가 지속 가능한 화학물질이 되기 위해서는 이온성 액체의 생물학적 행동에 대한 평가가 반드시 수행되어야 한다. 그러므로 본 연구자는 전세계적으로 데이터가 미흡한 이온성 액체의 생태독성과 생 분해성에 대한 조사를 실시 하였다. 음이온으로 bromide 결합하고 각각 알킬 체인의 길이가 3, 4, 6, 8개인 양이온 1-alkyl-3-methylimidazolium, 1-alkyl-3-methylpyridinium, 1-alkyl-1-methylpyrrolidinium의 독성을 측정하기 위하여 미세 녹조류 (Pseudokirchneriella subcapitata)를 선정하였다. 독성 측정방법으로는 OECD [Organization for Economic Cooperation and Development] 와 EPA [Environmental Protection Agency]에서 참조된 성장반응 실험이 실시 되었으며, 조류의 광합성 특성을 기초로 고안된 독성 측정장치를 통해 이루어졌다. 실험결과 두 가지 실험 방법에서 양이온의 종류에 관계없이 알킬 체인의 길이가 증가할수록 독성이 증가되는 것을 확인할 수 있었다. 양이온의 종류에 따른 독성 평가 경우, imidazolium과 pyridinium이 pyrrolidinium보다 독성이 더 강하게 측정되어서 실험된 이온성 액체 중 pyrrolidinium이 가장 친환경적 화학구조를 가진 것으로 판단할 수 있었다. 폐수나 하수 처리공정에서 이온성 액체의 처리 가능성과 분해과정을 확인하기 위하여 생 분해성 실험을 실시하였다. 활성오니는 전주시 하수처리장에서 채취하였으며 2 달간의 시간 동안 이온성 액체의 생 분해성 과정을 HPLC와 LC-MS로 측정하였다. 실험결과 dialkylimidazolium과 dialkylpyridinium 염은 각기 다른 알킬 체인 부분의 산화 과정을 통해 생 분해 된 것을 확인 할 수 있었다. Imidazolium염의 경우 1-(1-hydroxybutyl)-3-methylimidazolium, 1-(3-hydroxybutyl)-3-methylimidazolium, 1-butyl-3-hydroxymethyl imidazolium, 1-methyl-3-(3-oxobutyl)imidazolium, methylimidazole, butylimidazole의 중간체를 관찰할 수 있었으며, pyridinium의 경우 1-hydroxybutyl-3-methylpyridinium, 1-(2-hydroxybutal)-3-methylpyridinium, 1-(2-hydroxyethyl)-3-methylpyridinium and methylpyridine의 중간체를 확인할 수 있었다.

      • 종양의 면역세포 치료를 위해 CD40-B세포를 이용한 종양항원 특이 자가 세포독성 T림프구의 생성

        NGUYEN PHAM THANH NHAN 전남대학교 대학원 2007 국내석사

        RANK : 247374

        Cell-based immunotherapy using professional antigen presenting cells (APC) which are used to elicit T cell immunity is a promising alternative treatment modalities for cancer. Dendritic cells (DC) have several critical limitations, although highly efficient in their capacity to induce T-cell responses. So, alternative sources of APCs should be considered. We established a culture system to generate CD40-activated B cells (CD40-B cells) and investigated the ability of CD40-B cells as an APC to induce antigen specific cytotoxic T lymphocytes for cancer immunotherapy. To generate CD40-B cells, peripheral blood mononuclear cells were co-cultured with CD40L-transfected J558 cell line in the presence of IL-4. After 14 days of culture these cells were highly activated and consistently expressed a high density of cell surface molecules involved in APC function. The endocytosis assay clearly showed that these cells were capable of taking up antigen through their mannose receptors. CD40-B cells showed potent allostimulatory capacity in a manner dependent on the effector cells to T-cell ratio. CD40-B cells pulsed with tumor cell lysates induced antigen-specific cytotoxic T lymphocytes (CTLs) ex vivo, and these CTLs secreted interferon-γ and killed target tumor cells. Therefore, CD40-B cells are excellent source of professional antigen presenting cells for antigen specific immunotherapy.

      • Pharmacokinetic Study and Metabolism of Disopyramide in Rat

        Khoa, Pham Quynh Kangwon National University 2018 국내석사

        RANK : 247374

        Disopyramide (DSP) has long been indicated for treatment of ventricular tachycardia. In the circulatory system, the concentration-dependent binding extent of DSP and its metabolites to α-1 acid glycoprotein (AAG) has been reported. In human, DSP is mainly metabolised under N-dealkylation reaction in liver to form mono-isopropyl-disopyramide (M-iso-D) via CYP3A4, leading to its interaction with CYP3A4-metabolized drugs such as erythromycin, clarithromycin, or garenoxacin. In contrast, in animals, DSP’s metabolism is dominated both by N-dealkylation and hydroxylation reactions. The multiple reaction monitoring (MRM) approach was applied to identification of DSP’s metabolites in rat urine. Besides, liquid chromatography (LC) tandem mass spectrometry (MS/MS) technique was used to quantitate DSP and its major metabolite in rat plasma after it was fully validated according to guidelines of FDA and EMA. Their pharmacokinetic parameters were derived from the data after oral and intravenous administration of DSP at 25 and 5 mg/kg respectively. Also, the excretion profiles of DSP and its major metabolite were examined during 72 h in rat urine. In this study, seventeen predicted metabolites of DSP were detected as results of various metabolic reactions involved in metabolism of DSP, of these metabolites, M-iso-D was also found with the highest proportion (6.19%) in rat urine. In addition, a successfully developed and fully validated LC-MS/MS assay for the simultaneous determination of DSP and its major metabolite in rat plasma in accordance with the guidelines of FDA and EMA and was successfully applied to pharmacokinetic studies of DSP, and M-iso-D which showed that half-life values of DSP and M-iso-D were 3 and 1.9 h after oral administration together with 1.5 and 0.8 h following intravenous administration respectively, and the clearance and absolute bioavailability of DSP were 8510 ml/h/kg and 70.96%. Additionally, excretion profiling study of DSP and M-iso-D using this method indicated that the renal excretion of DSP and M-iso-D was almost complete in 24 h and 31.64% of the oral dose absorbed was excreted as unchanged DSP and as to M-iso-D, the percentage was 4.12%. The attained results suggested that M-iso-D found in rat was the major metabolite of DSP as well. To our knowledge, the LC-MS/MS assay developed in this study was better than methods mentioned in previous reports in sensitivity, selectivity, simplification, linearity and throughput. Although there was difference between the present and previous studies in pharmacokinetic parameters, the results were understandable because of the concentration-dependent protein-bound DSP’s characteristic, its high oral and intravenous doses, resulting in protein-unbound DSP in higher concentration for distribution, metabolism and excretion.

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