• Asian-Australasian Journal of Animal Sciences
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• 제33권2호
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• pp.360-372
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• 2020

Objective: Specific genomic sites can be recognized and permanently modified by genome editing. The discovery of endonucleases has advanced genome editing in pigs, attenuating xenograft rejection and cross-species disease transmission. However, off-target mutagenesis caused by these nucleases is a major barrier to putative clinical applications. Furthermore, off-target mutagenesis by genome editing has not yet been addressed in pigs. Methods: Here, we generated genetically inheritable α-1,3-galactosyltransferase (GGTA1) knockout Yucatan miniature pigs by combining transcription activator-like effector nuclease (TALEN) and nuclear transfer. For precise estimation of genomic mutations induced by TALEN in GGTA1 knockout pigs, we obtained the whole-genome sequence of the donor cells for use as an internal control genome. Results: In-depth whole-genome sequencing analysis demonstrated that TALEN-mediated GGTA1 knockout pigs had a comparable mutation rate to homologous recombination-treated pigs and wild-type strain controls. RNA sequencing analysis associated with genomic mutations revealed that TALEN-induced off-target mutations had no discernable effect on RNA transcript abundance. Conclusion: Therefore, TALEN appears to be a precise and safe tool for generating genomeedited pigs, and the TALEN-mediated GGTA1 knockout Yucatan miniature pigs produced in this study can serve as a safe and effective organ and tissue resource for clinical applications.

• 조명전기설비학회논문지
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• 제20권10호
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• pp.151-157
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• 2006

생활수준이 향상 될수록 로봇이 인간의 노동을 대신하는 요소는 더욱 많아지고 있다. 하지만 대부분의 로봇이 지면에 고정된 장치산업에 국한되어 있기 때문에, 폭넓은 응용가치가 기대되는 휴먼 로봇에 대한 필요성이 강조되고 있다. 휴먼로봇은 사람을 대신하기 위한 목적으로 많은 연구가 진행되고 있지만, 관련 하드웨어의 부족으로 매우 단순하고 제한적으로 적용되고 있다. 이러한 한계를 극복하기 위해 본 연구에서는 기구학적인 메커니즘과 제어장치를 개발하여, 어깨와 팔을 3자유도 형태로 마스트 암을 구성하고, 관절변수의 특성과 엔드-이펙터 궤적실험을 통하여 사람과 유사한 동작을 재현하였다.

• IMMUNE NETWORK
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• 제10권5호
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• pp.153-163
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• 2010

Background: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified $CD43^{lo}$ and $CD43^{hi}$ cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to $CD43^{hi}$ effector cells, $CD43^{lo}$ effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. $CD43^{lo}$ effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of $CD43^{lo}$ CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

• 한국정밀공학회지
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• 제19권4호
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• pp.187-194
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• 2002

In this paper, a motion control algorithm is developed using a fuzzy control and the optimization of performance function, which makes a robot arm avoid an unexpected obstacle when the end-effector of the robot arm is moving to the goal position. During talc motion, if there exists no obstacle, the end-effector of the robot arm moves along the predefined path. But if these exists an obstacle and close to talc robot arm, the fuzzy motion controller is activated to adjust the path of the end-effector of the robot arm. Then, the robot arm takes the optimal posture far collision avoidance with the obstacle. To show the feasibility of the developed algorithm, numerical simulations are carried out with changing both the positions and sites of obstacles. It was concluded that the proposed algorithm gives a good performance for obstacle avoidance.

• Molecules and Cells
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• 제39권9호
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• pp.687-691
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• 2016

Transcription activator-like effector nucleases (TALENs) are powerful tools for targeted genome editing in diverse cell types and organisms. However, the highly identical TALE repeat sequences make it challenging to assemble TALEs using conventional cloning approaches, and multiple repeats in one plasmid are easily catalyzed for homologous recombination in bacteria. Although the methods for TALE assembly are constantly improving, these methods are not convenient because of laborious assembly steps or large module libraries, limiting their broad utility. To overcome the barrier of multiple assembly steps, we report a one-step system for the convenient and flexible assembly of a 180 TALE module library. This study is the first demonstration to ligate 9 mono-/dimer modules and one circular TALEN backbone vector in a one step process, generating 9.5 to 18.5 repeat sequences with an overall assembly rate higher than 50%. This system makes TALEN assembly much simpler than the conventional cloning of two DNA fragments because this strategy combines digestion and ligation into one step using circular vectors and different modules to avoid gel extraction. Therefore, this system provides a convenient tool for the application of TALEN-mediated genome editing in scientific studies and clinical trials.

• 제어로봇시스템학회논문지
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• 제22권6호
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• pp.389-396
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• 2016

The sealing robot must be able to calculate the slope of a contact surface for complete adherence of the sealing on different concrete shapes. After the slope is obtained, the robot will track on the surface of the concrete, but this process contains an error in the actual purpose of the force command. The reason this a phenomenon occurs, the non-linearity of the contact surface and the end-effector, is due to parasitic coupling. Errors like make it difficult to measure accurately the respective factors. Therefore, it is regarded as a disturbance that occurs when it follows the work surface it. In this paper, we selected the friction coefficient of the surface as a control factor and designed a compensator to reduce effects of disturbance. Finally, in view of the non-linearity of the end-effector of a robot to contact surfaces directly, we propose a robust force tracking controller in the finite range for managing disturbances that occur during the sealing.

• Journal of Korean Neurosurgical Society
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• 제66권4호
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• pp.356-381
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• 2023

Although immunotherapy has been broadly successful in the treatment of hematologic malignancies and a subset of solid tumors, its clinical outcomes for glioblastoma are still inadequate. The results could be due to neuroanatomical structures such as the blood-brain-barrier, antigenic heterogeneity, and the highly immunosuppressive microenvironment of glioblastomas. The antitumor efficacy of endogenously activated effector cells induced by peptide or dendritic cell vaccines in particular has been insufficient to control tumors. Effector cells, such as T cells and natural killer (NK) cells can be expanded rapidly ex vivo and transferred to patients. The identification of neoantigens derived from tumor-specific mutations is expanding the list of tumor-specific antigens for glioblastoma. Moreover, recent advances in gene-editing technologies enable the effector cells to not only have multiple biological functionalities, such as cytokine production, multiple antigen recognition, and increased cell trafficking, but also relieve the immunosuppressive nature of the glioblastoma microenvironment by blocking immune inhibitory molecules, which together improve their cytotoxicity, persistence, and safety. Allogeneic chimeric antigen receptor (CAR) T cells edited to reduce graft-versus-host disease and allorejection, or induced pluripotent stem cell-derived NK cells expressing CARs that use NK-specific signaling domain can be a good candidate for off-the-shelf products of glioblastoma immunotherapy. We here discuss current progress and future directions for T cell and NK cell therapy in glioblastoma.

• IMMUNE NETWORK
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• 제23권1호
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• pp.7.1-7.27
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• 2023

The mammalian intestines harbor trillions of commensal microorganisms composed of thousands of species that are collectively called gut microbiota. Among the microbiota, bacteria are the predominant microorganism, with viruses, protozoa, and fungi (mycobiota) making up a relatively smaller population. The microbial communities play fundamental roles in the maturation and orchestration of the immune landscape in health and disease. Primarily, the gut microbiota modulates the immune system to maintain homeostasis and plays a crucial role in regulating the pathogenesis and pathophysiology of inflammatory, neuronal, and metabolic disorders. The microbiota modulates the host immune system through direct interactions with immune cells or indirect mechanisms such as producing short-chain acids and diverse metabolites. Numerous researchers have put extensive efforts into investigating the role of microbes in immune regulation, discovering novel immunomodulatory microbial species, identifying key effector molecules, and demonstrating how microbes and their key effector molecules mechanistically impact the host immune system. Consequently, recent studies suggest that several microbial species and their immunomodulatory molecules have therapeutic applicability in preclinical settings of multiple disorders. Nonetheless, it is still unclear why and how a handful of microorganisms and their key molecules affect the host immunity in diverse diseases. This review mainly discusses the role of microbes and their metabolites in T helper cell differentiation, immunomodulatory function, and their modes of action.

• 융합신호처리학회논문지
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• 제15권3호
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• pp.104-111
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• 2014

이 논문에서는 자동차의 제동장치에 사용되는 브레이크 모듈 조립 작업을 로봇을 사용하여 자동화한 사례를 소개한다. 브레이크 모듈은 하나의 토크 멤버에 두 개의 브레이크 패드와 두 개의 패드 라이너를 장착하여 조립을 완성한다. 이 조립 작업은 로봇의 방향을 자주 바꾸어 주어야하기 때문에 일반적인 산업용 로봇 핸드를 사용하면 조립 시간이 오래 걸린다. 이 논문에서는 두 가지 방법을 제안한다. 첫 번째 방법은 다섯 개의 그리퍼를 갖는 로봇 엔드 이펙터를 설계, 제작하여 기존의 산업용 6축 머니퓰레이터에 장착하여 조립 작업을 수행하는 방법이다. 이 방법에서는 두 개의 브레이크 패드와 두 개의 패드 라이너를 한꺼번에 파지하여 조립 작업을 수행하며 따라서 하나의 그리퍼 만을 가지고 있는 기존의 엔드 이펙터에 비해 조립 시간을 줄일 수 있었다. 두 번째 방법에서는 첫 번째 방법을 더욱 개선하여 엔드 이펙터가 하나의 부가적인 자유도를 가지도록 설계, 제작하여 기존의 산업용 6축 머니퓰레이터에 장착하였다. 이 방법에서는 전체 로봇 머니퓰레이터가 7 자유도를 갖는 여유자유도 머니퓰레이터가 되어 로봇의 동작을 최소화하면서 조립에 필요한 다양한 로봇 방향을 구현할 수 있었다.

• IMMUNE NETWORK
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• 제21권5호
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.