• Title/Summary/Keyword: iNPC

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Induced neural stem cells from human patient-derived fibroblasts attenuate neurodegeneration in Niemann-Pick type C mice

  • Hong, Saetbyul;Lee, Seung-Eun;Kang, Insung;Yang, Jehoon;Kim, Hunnyun;Kim, Jeyun;Kang, Kyung-Sun
    • Journal of Veterinary Science
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    • v.22 no.1
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    • pp.7.1-7.13
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    • 2021
  • Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

Effect of Pulse Width Modulation Methods on Power Losses and Thermal Loadings of Single-Phase 5-Level NPC Inverters for PV Systems (전압 변조 방법에 따른 단상 5-레벨 NPC 태양광 인버터의 전력 손실 및 열 부하 분석)

  • Ryu, Taerim;Choi, Ui-Min
    • The Transactions of the Korean Institute of Power Electronics
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    • v.27 no.1
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    • pp.56-62
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    • 2022
  • In this paper, the effect of pulse width modulation methods on thermal loadings and power losses of single-phase five-level NPC inverters for photovoltaic systems are analyzed. The pulse width modulation methods affect the power losses of the NPC inverters and thus lead to different thermal loadings of NPC inverters. To identify the reliability-critical power device with respect to thermal stress, the thermal loadings of I- and T-type NPC inverters are analyzed by applying the unipolar pulse modulation method. Then, the effect of the discontinuous pulse width modulation method on power losses and thermal loadings of power devices of I- and T-type NPC inverters are analyzed. Finally, the operation of NPC inverters applying the discontinuous pulse modulation method is confirmed by experiments. The results show that the discontinuous pulse modulation method is able to improve the reliability of NPC inverters by reducing thermal loadings of reliability-critical power devices and it is more effective for T-type NPC inverters than I-type NPC inverters.

Flexible Development Architecture for Game NPC Intelligence to Support Load Sharing and Group Behavior (게임NPC지능 개발을 위한 부하분산과 그룹 행동을 지원하는 유연한 플랫폼 구조)

  • Im Cha-Seop;Kim Tae-Yong
    • Journal of the Institute of Electronics Engineers of Korea CI
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    • v.43 no.2 s.308
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    • pp.40-51
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    • 2006
  • As computer games become more complex and consumers demand more sophisticated computer controlled NPCs, developers are required to place a greater emphasis on the artificial intelligence aspects for their games. The platform for game NPC Intelligence Development should support real-time, independence, flexibility, group behavior, and various A.I to NPC that are reactive, realistic and easy to develop. This paper presents an architecture to satisfy these criteria for the platform of game NPC intelligence development. The proposed platform shows the higher performance than existing platform through the load sharing, and it also has some advantages which are supporting the various AI techniques, efficient group behavior, and independence to develop NPC intelligence.

Overmodulation Operation of SVM for NPC Type 3-Level Inverter (NPC형 3레벨 인버터의 공간벡터 과변조운전)

  • Lee, Jae-Moon;Choi, Jae-Ho
    • The Transactions of the Korean Institute of Power Electronics
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    • v.13 no.1
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    • pp.22-32
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    • 2008
  • This paper proposes a linearization technique for the 3-level NPC type inverter, which increases the linear control range of Inverter up to the one-pulse inverter. The overmodulation range is divided into two modes depending on the Modulation Index, MI. In overmodulation region I, the reference angles are derived from the fourier series expansion of the reference voltage corresponding to the MI. In overmodulation region II, the holding angles are also derived in the same way. Therefore, it is possible to obtain the linear control and the maximized utilization of PWM inverter output voltage.

Prototype of Procedural Quest Generation in Persistent RPG via Non-Player Character (영속적 RPG 게임에서 NPC중심의 창발적 서사 생성 연구)

  • Jeong, Bo-Gyun;Ryu, Eun-Seok;Kang, Sin-Jin
    • Proceedings of the Korean Society of Computer Information Conference
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    • 2014.01a
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    • pp.49-50
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    • 2014
  • 본 논문은 영속적 RPG게임에서 사용자에게 제공되는 퀘스트 유형의 절차적 생성 기법에 대한 연구이다. 영속적 월드(persistent world) 환경은, 게임 사용자를 포함한 다양한 게임 구성 자원간의 상호작용을 통해 서사를 생성하는 가상 월드의 특징을 가지고 있다. 본 실험은 서사의 핵심 자원인 NPC(Non-Player Character) 및 다양한 월드 자원들을 가진 가상의 영속적 월드 하에, NPC들이 창발적인 퀘스트를 지속적으로 생성하도록 하였다. 이를 통해 영속적 가상 월드의 NPC 자원들이 곳곳에서 창발적 퀘스트 유형을 지속적으로 생성하는 것을 확인 할 수 있었다.

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A Study on High-level Pathfinding Algorithm in Side View 2D Games (사이드 뷰 2D 게임에서의 고수준 길찾기 알고리즘에 대한 연구)

  • Hwan-Jin You;Bum-Ro Lee
    • Proceedings of the Korean Society of Computer Information Conference
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    • 2023.07a
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    • pp.167-170
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    • 2023
  • 게임 플랫폼의 고도화와 게임 구현 기술의 발전을 통해 이루어지고 있는 개발 환경의 효율성 제고를 통해 이전에 게임의 구현 자체에 소요하는 시간을 게임 콘텐츠의 질적 향상을 위해 투입할 수 있는 여건이 형성되고 있다. 본 논문은 게임에서 등장하는 NPC가 보다 사실적인 추론을 통해 플레이어를 추적하도록 지정하는 알고리즘을 고수준의 카테고리로 구분하여 구현하여, 개발 과정에서의 NPC 구현에 효율성을 제고하는 기법을 제안한다. NPC가 플레이를 추적하는 스토리를 기반으로 하는 게임에서 NPC가 플레이어의 위치에 도달하기 위한 길찾기 알고리즘은 필수적이다. 일반적으로 사용되는 최단 거리 길찾기 알고리즘인 다익스트라(Dijkstra)의 경우, 효율적이지만 플레이어가 NPC의 경로를 예측 가능할 수 있기에 게임의 재미 향상에 걸림돌이 되는 단점이 있다. 본 논문에서는 최단 거리 길찾기를 구현하면서 다양한 게임 스토리 상의 설정으로 지정할 수 있는 다양한 방법론을 연구하였으며, 이를 구현하기 위한 고수준 길찾기에 대한 방법을 제시한다.

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Dihydroaustrasulfone alcohol induces apoptosis in nasopharyngeal cancer cells by inducing reactive oxygen species-dependent inactivation of the PI3K/AKT pathway

  • Kok-Tong Tan;Yu-Hung Shih;Jiny Yin Gong;Xiang Zhang;Chiung-Yao Huang;Jui-Hsin Su;Jyh-Horng Sheu;Chi-Chen Lin
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.383-398
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    • 2023
  • Dihydroaustrasulfone alcohol (DA), the synthetic precursor of a natural compound (austrasulfone) isolated from the coral species Cladiella australis, has shown cytotoxic effects against cancer cells. However, it is unknown whether DA has antitumor effects on nasopharyngeal carcinoma (NPC). In this study, we determined the antitumor effects of DA and investigated its mechanism of action on human NPC cells. The MTT assay was used to determine the cytotoxic effect of DA. Subsequently, apoptosis and reactive oxygen species (ROS) analyses were performed by using flow cytometry. Apoptotic and PI3K/AKT pathway-related protein expression was determined using Western blotting. We found that DA significantly reduced the viability of NPC-39 cells and determined that apoptosis was involved in DA-induced cell death. The activity of caspase-9, caspase-8, caspase-3, and PARP induced by DA suggested caspase-mediated apoptosis in DA-treated NPC-39 cells. Apoptosis-associated proteins (DR4, DR5, FAS) in extrinsic pathways were also elevated by DA. The enhanced expression of proapoptotic Bax and decreased expression of antiapoptotic BCL-2 suggested that DA mediated mitochondrial apoptosis. DA reduced the expression of pPI3K and p-AKT in NPC-39 cells. DA also reduced apoptosis after introducing an active AKT cDNA, indicating that DA could block the PI3K/AKT pathway from being activated. DA increased intracellular ROS, but N-acetylcysteine (NAC), a ROS scavenger, reduced DA-induced cytotoxicity. NAC also reversed the chances in pPI3K/AKT expression and reduced DA-induced apoptosis. These findings suggest that ROS-mediates DA-induced apoptosis and PI3K/AKT signaling inactivation in human NPC cells.

Evaluation of Risk Factors for Nasopharyngeal Carcinoma in a High-risk Area of India, the Northeastern Region

  • Lourembam, Deepak Singh;Singh, Asem Robinson;Sharma, T. Dhaneshor;Singh, Th Sudheeranjan;Singh, Thiyam Ramsing;Singh, Lisam Shanjukumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4927-4935
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    • 2015
  • Northeastern India is a major nasopharyngeal carcinoma (NPC) high risk-area although the rest of the country has very low incidence. A case-control study of 105 NPC cases and 115 controls was conducted to identify the potential risk factors for NPC development in this region. Information was collected by interviewer about socio-demographic characteristics, cigarette smoking, alcohol consumption, dietary history, occupational history, and a family history of cancer. Epstein-Barr viral load was assayed from the blood DNA by real time PCR. Associations between GSTs genotypes, cytochrome P450 family including CYP1A1, CYP2E1 and CYP2A6 polymorphisms and susceptibility to relationship between the diseases were studied using PCR-RFLP assay. Results indicate that Epstein-Barr virus load was significantly higher in patients compared to controls (p<0.0001). Furthermore, concentration of blood EBV-DNA was significantly higher in advanced stage disease (Stage III and IV) than in early stage disease (Stage I and II) (p<0.05). Presence of CYP2A6 variants that reduced the enzyme activity was significantly less frequent in cases than controls. Smoked meat consumption, exposure to smoke, living in poorly ventilated house and alcohol consumption were associated with NPC development among the population of Northeastern India. Thus, overall our study revealed that EBV viral load and genetic polymorphism of CYP2A6 along with living practices which include smoked meat consumption, exposure to smoke, living in poorly ventilated houses and alcohol consumption are the potential risk factors of NPC in north eastern region of India. Understanding of the risk factors and their role in the etiology of NPC are helpful forpreventive measures and screening.

Transferrin Receptors in the Liver Cell Membrane of Carcinogen (3-methyl-4-dimethyl-arninoazobenzene) Treated Rat (Carcinogen (3-methyl-4-dimethyl-aminoazo benzene) 처리후 간세포막에서의 Transferrin Receptor 변동에 관한 연구)

  • Lee, Jae-Heun;Ro, Eu-Sun;Hur, Gang-Min;Lee, Choong-Sik;Seok, Jeong-Ho
    • The Korean Journal of Pharmacology
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    • v.29 no.1
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    • pp.85-96
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    • 1993
  • To investigate the alteration of transferrin receptor (TfR) in the proliferating or transformed liver cells, $^{125}I-transferrin$ binding experiment was carried out in the isolated parenchymal cells (PC) or nonparenchymal cells (NPC) from normal regenerated rat liver after partial hepatectomy and from the liver of 3-methyl-4-dimethyl-aminoazobenzene (3-Me-DAB) treated rat. With the administration of 3-Me-DAB for 8 weeks, the liver tissue showed marked morphologic changes of oval cell proliferation, regenerations of hepatocytes, and atypical proliferations of bile ducts, but these changes were little affected by partial hepatectomy. Transferrin binding values in PC or NPC homogenate from the regenerated liver of normal rat, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With the treatement of 3-Me-DAB for 8 weeks, transferrin binding sites in homogenates were higher than those of normal rat liver and increased by 7th day after partial hepatectomy. Transferrin binding sites (Bmax) in the cell membrane of NPC were higher than those of PC of normal rat liver, but there was no significant difference in Kd values between both groups (5.05, 6.3 nM). In the normal resenerated rat liver, transferrin binding sites in the PC or NPC plasma membrane, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With 3-Me-DAB tratment, transferrin binding sites in both liver NPC and PC plasma membrane were increased about 3 folds, compared to those in each plasma membrane of normal rat liver. And after partial hepatectomy of 3-Me-DAB trated rat, transferrin binding sites were increased by the 3rd day in the NPC plasma membrane but increased by the 7th day in the PC plasma membrane. In the transferrin binding sites of the PC or NPC plasma membrane of 3-Me-DAB treated liver, two kinds of Kd values $(3.1{\sim}4.7\;nM,\;25.4{\sim}54.1\;nM)$ were detected. The present results suggest that 1) TfRs are distributed in the liver PC as well as NPC; 2) Increased TfRs in PC or NPC plasma membrane of normal regenerated liver after partial hepatectomy and 3-Me-DAB treated rat liver, may be due to increased intracellular synthesis; 3) Increased TfRs in normal regenerated liver after partial hepatectomy might be related to the expression of a single type of high affinity site $(Kd,\;3.1{\sim}7.5\;nM)$, but in 3-Me-DAB treated rat liver might be related to the expression of high and low affinity types of receptors $(Kd,\;25.4{\sim}54.1\;nm)$.

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A Design of Effective NPC AI Patterns Using the Theory of 'Flow' and FSM in the Adventure Game (어드벤처 게임에서 몰입이론과 FSM을 이용한 효과적인 NPC AI 패턴 설계)

  • Oh, Se-Woong;Kang, Hee-Min;Cho, Young-Jin;Lim, Man-Sik;Kim, Sang-Muk;Lee, Jong-Beom;Sin, Ko-Eun;Lee, Ji-Hoon;Kang, Myung-Ju;Park, Chan-Il;Lee, Jong-Won;Oh, Hyoun-Ju;Kim, Sang-Jung
    • Proceedings of the Korean Society of Computer Information Conference
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    • 2014.07a
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    • pp.297-301
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    • 2014
  • 게임에는 많은 종류의 장르가 있다. 어떤 장르의 게임이 되었건 플레이어와 많은 상호작용을 하는 A.I는 게임에 있어 중요한 요소 이며 어드벤처 게임(Adventure Game) 장르도 예외는 아니다. A.I(Artificial Intelligence)I의 행동이나 상황에 따른 플레이어와의 상호작용은 게임에 있어 플레이어에게 몰입감을 주며 게임을 좀 더 현실감 있게 해주는 게임의 수많은 요소 중 하나다. 본 논문에서는 FSM(Finite-State Machine) 기법을 사용하여 어드벤처 게임에서플레이어에게 '몰입'을 유발 시키는 방법으로 FSM 기법의 NPC(None-Player Character) A.I 패턴을 디자인을 통해 플레이어의 '몰입'을 유발 하였다.

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