• Asian-Australasian Journal of Animal Sciences
• /
• v.33 no.2
• /
• pp.360-372
• /
• 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.

• Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
• /
• v.20 no.10
• /
• pp.151-157
• /
• 2006

As people's living standard is being improved, human works are being replaced by robots. However, because most robots are used in process industry, fixed on the ground, we need to develop human robots that have wide applications. Currently many researches are being conducted on human robots with the object of replacing human works, but because of lack of relevant hardware, such robots are being applied limitedly to very simple tasks. To overcome the limitation, the present study developed a kinematical mechanism and a controller. Based on human kinematics, the shoulders and the arms were composed of master arms with 3 degree of freedom, and we reproduced motions similar to human ones through the characteristics of joint variables and experiment on the trajectory of the end effector.

• IMMUNE NETWORK
• /
• v.10 no.5
• /
• pp.153-163
• /
• 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.

• Journal of the Korean Society for Precision Engineering
• /
• v.19 no.4
• /
• pp.187-194
• /
• 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
• /
• v.39 no.9
• /
• pp.687-691
• /
• 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.

• Journal of Institute of Control, Robotics and Systems
• /
• v.22 no.6
• /
• pp.389-396
• /
• 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
• /
• v.66 no.4
• /
• pp.356-381
• /
• 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
• /
• v.23 no.1
• /
• pp.7.1-7.27
• /
• 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.

• Journal of the Institute of Convergence Signal Processing
• /
• v.15 no.3
• /
• pp.104-111
• /
• 2014

In this paper, we deal with robotic automation for assembling car brake modules. A car brake module is comprises of a torque member, two brake pads, and two pad liners. In the assembly process, brake pads and pad liners are needed to be inserted in a torque member. If we use a typical robotic hand for the assembly, task time takes too long. So, we propose two methods. The first method is to use an end effector that has five grippers capable of gripping five assembly parts. In the first method we attached the implemented end effector to a conventional 6 degrees of freedom industrial manipulator and performed the bake module assembly task. Experimental results show that the task time is remarkably reduced. The brake module assembly task needs the robot to change its orientation frequently, so, in the second method, we added one degree of freedom to the end effector that is used in the first method. By attaching it to a conventional 6 degrees of freedom industrial manipulator, we composed a 7 degrees of freedom redundant manipulator. A redundant manipulator has the advantage of flexible manipulation so the robot can change its orientation easily and can perform assembly task very fast. Experimental results show that the second method dramatically reduce whole task time for brake module assembly.

• IMMUNE NETWORK
• /
• v.21 no.5
• /
• pp.33.1-33.19
• /
• 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.