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Acetaminophen (APAP)-induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. Autophagy is a degradative process by which various cargoes are collected by the autophagic receptors such as p62/SQSTSM-1/Sequestosome-1 for lysosomal degradation. Here, we investigated the protective role of p62-dependent autophagy in APAP-induced liver injury.APAP-induced hepatotoxicity was induced by a single i.p. injection of APAP (500 mg/kg) in C57/BL6 male mice. YTK-2205 (20 mg/kg), a p62 agonist targeting ZZ domain, was co- or post-administered with APAP. Western blotting and immunocytochemistry were performed to explore the mechanism.N-terminal arginylation of the molecular chaperone calreticulin retro-translocated from the endoplasmic reticulum (ER) was induced in the livers undergoing APAP-induced hepatotoxicity, and YTK-2205 exhibited notable therapeutic efficacy in acute hepatotoxicity as assessed by the levels of serum alanine aminotransferase and hepatic necrosis. This efficacy was significantly attributed to accelerated degradation of ubiquitin (Ub) conjugates as well as damaged mitochondria (mitophagy) and ER (ER-phagy). In primary murine hepatocytes treated with APAP, YTK-2205 induced the co-localization of p62Our results elucidated that p62-dependent autophagy plays a key role in the removal of cytotoxic materials such as damaged mitochondria in APAP-induced hepatotoxicity. Small molecule ligands to p62 may be developed into drugs to treat this pathological condition.

The N-degron pathway is a proteolytic system in which the N-terminal degrons (N-degrons) of proteins, such as arginine (Nt-Arg), induce the degradation of proteins and subcellular organelles via the ubiquitin-proteasome system (UPS) or macroautophagy/autophagy-lysosome system (hereafter autophagy). Here, we developed the chemical mimics of the N-degron Nt-Arg as a pharmaceutical means to induce targeted degradation of intracellular bacteria via autophagy, such as Salmonella enterica serovar Typhimurium (S. Typhimurium), Escherichia coli, and Streptococcus pyogenes as well as Mycobacterium tuberculosis (Mtb). Upon binding the ZZ domain of the autophagic cargo receptor SQSTM1/p62 (sequestosome 1), these chemicals induced the biogenesis and recruitment of autophagic membranes to intracellular bacteria via SQSTM1, leading to lysosomal degradation. The antimicrobial efficacy was independent of rapamycin-modulated core autophagic pathways and synergistic with the reduced production of inflammatory cytokines. In mice, these drugs exhibited antimicrobial efficacy for S. Typhimurium, Bacillus Calmette–Guérin (BCG), and Mtb as well as multidrug-resistant Mtb and inhibited the production of inflammatory cytokines. This dual mode of action in xenophagy and inflammation significantly protected mice from inflammatory lesions in the lungs and other tissues caused by all the tested bacterial strains. Our results suggest that the N-degron pathway provides a therapeutic target in host-directed therapeutics for a broad range of drug-resistant intracellular pathogens. Abbreviations: ATG: autophagy-related gene; BCG: Bacillus Calmette–Guérin; BMDMs: bone marrow-derived macrophages; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CFUs: colony-forming units; CXCL: C-X-C motif chemokine ligand; EGFP: enhanced green fluorescent protein; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; LIR: MAP1LC3/LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; Mtb: Mycobacterium tuberculosis; MTOR: mechanistic target of rapamycin kinase; NBR1: NBR1 autophagy cargo receptor; OPTN: optineurin; PB1: Phox and Bem1; SQSTM1/p62: sequestosome 1; S. Typhimurium: Salmonella enterica serovar Typhimurium; TAX1BP1: Tax1 binding protein 1; TNF: tumor necrosis factor; UBA: ubiquitin-associated.

In the N-degron pathway, N-recognins recognize cognate substrates for degradation via the ubiquitin (Ub)-proteasome system (UPS) or the autophagy-lysosome system (hereafter autophagy). We have recently shown that the autophagy receptor SQSTM1/p62 (sequestosome 1) is an N-recognin that binds the N-terminal arginine (Nt-Arg) as an N-degron to modulate autophagic proteolysis. Here, we show that the N-degron pathway mediates pexophagy, in which damaged peroxisomal fragments are degraded by autophagy under normal and oxidative stress conditions. This degradative process initiates when the Nt-Cys of ACAD10 (acyl-CoA dehydrogenase family, member 10), a receptor in pexophagy, is oxidized into Cys sulfinic (CysO2) or sulfonic acid (CysO3) by ADO (2-aminoethanethiol (cysteamine) dioxygenase). Under oxidative stress, the Nt-Cys of ACAD10 is chemically oxidized by reactive oxygen species (ROS). The oxidized Nt-Cys2 is arginylated by ATE1-encoded R-transferases, generating the RCOX N-degron. RCOX-ACAD10 marks the site of pexophagy via the interaction with PEX5 and binds the ZZ domain of SQSTM1/p62, recruiting LC3+-autophagic membranes. In mice, knockout of either Ate1 responsible for Nt-arginylation or Sqstm1/p62 leads to increased levels of peroxisomes. In the cells from patients with peroxisome biogenesis disorders (PBDs), characterized by peroxisomal loss due to uncontrolled pexophagy, inhibition of either ATE1 or SQSTM1/p62 was sufficient to recover the level of peroxisomes. Our results demonstrate that the Cys-N-degron pathway generates an N-degron that regulates the removal of damaged peroxisomal membranes along with their contents. We suggest that tannic acid, a commercially available drug on the market, has a potential to treat PBDs through its activity to inhibit ATE1 R-transferases. Abbreviations: ACAA1, acetyl-Coenzyme A acyltransferase 1; ACAD, acyl-Coenzyme A dehydrogenase; ADO, 2-aminoethanethiol (cysteamine) dioxygenase; ATE1, arginyltransferase 1; CDO1, cysteine dioxygenase type 1; ER, endoplasmic reticulum; LIR, LC3-interacting region; MOXD1, monooxygenase, DBH-like 1; NAC, N-acetyl-cysteine; Nt-Arg, N-terminal arginine; Nt-Cys, N-terminal cysteine; PB1, Phox and Bem1p; PBD, peroxisome biogenesis disorder; PCO, plant cysteine oxidase; PDI, protein disulfide isomerase; PTS, peroxisomal targeting signal; R-COX, Nt-Arg-CysOX; RNS, reactive nitrogen species; ROS, reactive oxygen species; SNP, sodium nitroprusside; UBA, ubiquitin-associated; UPS, ubiquitinproteasome system.

Defects in the nuclear lamina occur during physiological aging and as a result of premature aging disorders. Aging is also accompanied by an increase in transcription of genes encoding cytokines and chemokines, a phenomenon known as the senescence-associated secretory phenotype (SASP). Progerin and prelamin A trigger premature senescence and loss of function of human mesenchymal stem cells (hMSCs), but little is known about how defects in nuclear lamin A regulate SASP. Here, we show that both progerin overexpression and ZMPSTE24 depletion induce paracrine senescence, especially through the expression of monocyte chemoattractant protein-1 (MCP-1), in hMSCs. Importantly, we identified that GATA4 is a mediator regulating MCP-1 expression in response to prelamin A or progerin in hMSCs. Co-immunoprecipitation revealed that GATA4 expression is maintained due to impaired p62-mediated degradation in progerin-expressing hMSCs. Furthermore, depletion of GATA4 abrogated SASP-dependent senescence through suppression of NF-ĸB and MCP-1 in hMSCs with progerin or prelamin A. Thus, our findings indicate that abnormal lamin A proteins trigger paracrine senescence through a GATA4-dependent pathway in hMSCs. This molecular link between defective lamin A and GATA4 can provide insights into physiological aging and pathological aging disorders., Aging: Clues in nuclear proteins Abnormal versions of proteins that support the structure and function of the membrane of the cell nucleus are implicated in premature aging disorders, and also in normal aging. Researchers in South Korea led by Kyung-Sun Kang at Seoul National University investigated the protein network known as the nuclear lamina. They studied a specific type of human stem cell that gives rise to bone, cartilage, muscle and fat. They found that altering the levels of proteins produced by specific key genes promotes cell aging, and the alterations led to abnormalities in the proteins of the nuclear lamina. The researchers suggest that their work provides new insights into the molecular and cellular causes of premature and normal aging. Understanding the molecular triggers of aging could lead to treatments to delay both its normal and disease-linked forms.

Modeling of motion simulation of welding robot manipulator with external force interaction is studied in this paper. The modeling application of welding robot manipulator is for the welding of box girder on the offshore plant. Mechanical structure of robot arm consists of six rotational joints, thus the total degrees of freedom is six. Then, Denavit-Hartenberg method is used to solve kinematics of the mechanical structure of robot. Once kinematics is analyzed then dynamics is analyzed through the Lagrange's formulation with external force interaction model. We use optimization technique to create the motion of robot manipulator. In the optimization process, we set design variables, objective function, and constraints. The design variables are the joint angle profiles of robot manipulator for welding motion. The object function is multi objective function which is implemented in the summation of joint torque squares of each joint. Joint angle limits, torque limits, continuity condition, collision avoidance are imposed as time dependent and time independent constraints in optimization. All the joint space information include joint angle profiles, velocity profiles, acceleration profiles are obtained as optimal solution which can minimized joint torque to create the motion while the external force is interacted.

In this paper, a welding mobile manipulator for building offshore platforms is introduced. First of all, forward kinematics to analyze the relation between the joint angle inputs and the position and orientation of the end-effector is performed. Then, a motion planning algorithm using Jacobian is proposed. To solve a localization problem, a localization algorithm based on particle filters is applied. To verify the proposed methods, several simulations including a motion planning and localization simulations are performed. For a better welding motion, the optimal position of the mobile platform is proposed. Finally, the feasibility of the proposed welding robot system through an experiment is verified.

In this paper, kinematic modeling and singularity analysis are performed for an omnidirectional mobile robot. At the beginning, generalized formulas of the mobility and the first-order kinematics for a planar multiarticulated omnidirectional mobile robot are proposed. To verify the proposed formulas, a mobile robot that consists of three wheel mechanisms each of which has one redundant joint as compared to the operational degrees is introduced. Initially, the kinematic modeling and dynamic analysis, and odometry calculation for this robot are conducted. Next, singularity analysis of the proposed robot is performed. Then, using such a kinematic redundancy of each chain, motion planning algorithms that exploit the kinematic redundancy of the wheel chain are suggested. For navigation, a localization algorithm of the mobile robot based on odometry is presented, and specifically, two-leveled obstacle avoidance scheme, which simultaneously considers both large and small obstacles, is proposed. The usefulness of the proposed algorithms is verified through experimentation.

This paper presents a human detection algorithm and an obstacle avoidance algorithm for a marathoner service robot (MSR) that provides a service to a marathoner while training. To be used as a MSR, the mobile robot should have the abilities to follow a running human and avoid dynamically moving obstacles in an unstructured outdoor environment. To detect a human by a laser range finder (LRF), we defined features of the human body in LRF data and employed a support vector data description method. In order to avoid moving obstacles while tracking a running person, we defined a weighted radius for each obstacle using the relative velocity between the robot and an obstacle. For smoothly bypassing obstacles without collision, a dynamic obstacle avoidance algorithm for the MSR is implemented, which directly employed a real-time position vector between the robot and the shortest path around the obstacle. We verified the feasibility of these proposed algorithms through experimentation in different outdoor environments.

An automatic lighting system using 3-DOF robotic lamps and a laser scanner is proposed in this paper. The 3-DOF robotic lamp, which is designed with a spherical parallel mechanism with a unique forward kinematic solution, has a tilting motion to track a person and zoom-in and zoom-out motions to control the light intensity. In order to minimize the dynamic load, three actuators are installed at the base frame, and a counterbalancing design is considered. The positions of people are detected by a laser scanner, and the Kalman filter and a data association algorithm are applied in order to track the positions of people accurately. Therefore, multiple robotic lamps can track and illuminate each person continuously. We demonstrate experimentally that three robotic lamps mounted on the ceiling illuminate three people independently and control the intensity of the light according to the distance between a person and the robotic lamp.

This paper presents a localization algorithm for an unmanned forklift in a refrigerated warehouse. At the begging, an unmanned forklift and its environment are described and its kinematic analysis is conducted. For navigation in such a cold environment, a localization algorithm of a forklift based on particle filters with odometry and two magnetic sensors is presented. Finally, a path planning algorithm based on A-star search is applied to tasks in a refrigerated warehouse. The usefulness of the proposed algorithms is verified through simulations.

Robots are increasingly being used in situations such as search and rescue that require robust navigation capabilities, potentially in areas with little or no GPS or other high-quality localization information. As more robots are used in these scenarios, it becomes viable to collaborate between heterogeneous types of robots to leverage their individual strengths while minimizing their weaknesses. More specifically, in a scenario involving unmanned ground and aerial vehicles (UGV, UAV), the ground robot can contribute its high payload capacity to provide computational resources and high accuracy sensors while the aerial robot can bring its high mobility and capability to traverse obstacles to the team. However, in order for the team to benefit from these capabilities, it must be capable of generating a plan for both robots that allows them to collaboratively localize when necessary. Our approach to this problem is to combine a recently developed state lattice planner using controller-based motion primitives (SLC) with planning using adaptive dimensionality (PAD). The SLC planner allows for robust navigation using a wide variety of sensors including in areas with no or limited high-quality localization information while the PAD planner allows us to expand beyond a single robot and generate plans for a team of robots operating in a high dimensional space. We present our results to this combined approach for a UGV/UAV team operating indoors in areas with limited visual features.

The purpose of this study was to examine the impact of education for welldying on the death anxiety and death reception of care workers who were most closely linked to death among workers who were engaged in senior welfare. It`s basically meant to let care workers have a good understanding of death, death process and death-related factors to help elderly people close their life in a comfortable manner. The subjects in this study were the care workers who worked in J nursing home in the region of Gwangju. They received education in nine sessions, once a week, and the collected data were analyzed by the statistical package 15.0. The statistical analysis methods used in this study were reliability analysis, descriptive statistics analysis, t-test and ANOVA. The findings of the study were as follows: First, the welldying program participants showed a decrease in death anxiety. Second, the welldying program participants became more receptive to death.

In order determine potential correlations of multicultural family`s male spouses` bicultural stress and communication with their marital satisfaction, this study surveyed male spouses of foreign female participants in a variety of multicultural family assistance programs available at national marital immigrants assistance centers and healthy family assistance centers of Korea, The results of this survey can be summed up as follows: First, with regard to subordinate categories of bicultural stress, it was found that cultural shock (M

This paper presents a new control scheme of JAIST Active Robotic Walker (JARoW) developed to provide elderly people with sufficient ambulatory capability. Toward its practical use, our focus is placed on how to allow easier and reliable maneuverability by creating a natural user interface. Specifically, our challenge lies in providing a well-functioning controller by detecting what the user wants to do or their intentions. A Kalman filter based tracking scheme is realized to estimate and predict the locations of the user's legs and body in real time. The feedback control can then adjust the motions of JARoW corresponding to the actual user's walking behaviors. Our experiments confirm that JARoW can autonomously adjust its motion direction and velocity without requiring any additional control inputs.

This paper deals with a navigation algorithm for swarm robot systems in which multiple mobile robots work together. The motion of each mobile robot is modeled in such a way to have more inputs than the number of outputs. The null-space projection method of this model is employed to resolve the motion of the swarm robot system while avoiding obstacles. The feasibility of the proposed navigation algorithm is verified through a simulation study using several swarm robot models.

This work deals with navigation of an omni-directional mobile robot with active caster wheels. Initially, the posture of the omni-directional mobile robot is calculated by using the odometry information. Next, the position accuracy of the mobile robot is measured through comparison of the odometry information and the external sensor measurement. Finally, for successful navigation of the mobile robot, a motion planning algorithm that employs kinematic redundancy resolution method is proposed. Through experiments for multiple obstacles and multiple moving obstacles, the feasibility of the proposed navigation algorithm was verified.

The purpose of this study is to ascertain the effect of Art program for runaway Youths Self-esteem and Depression. Sstaying at the youth shelter located in Gwang ju. The subjects were assinged to two groups, an experimental group and a control group evenly. Coopersmith Self- Esteem Inventory was used measure the level of self-esteem, Beck Depression Inventory for depression. The collected data were analyzed by T-test according to the purpose of the study. The results of the study were as follows; The art program showed a positive effect on increasing the level of self-esteem and decreasing the level of depression of experimental group In comparison with those of control group.

In this paper, intelligent human tracking algorithms for a human moving at a high speed are proposed and applied to a marathoner service robot. Then an application using omni-directional mobile platform for the elderly or the disabled is introduced. To use various motions of omni-directional mobile robots, kinematic modeling and singularity analysis are performed.

This paper presents a novel application of a perception sensor Kinect to a mobile shopping cart (MSC). We attempt to exercise daily-used instructions as commands by using skeleton tracking of the Kinect sensor. A pair of differential-driven wheels together with dynamical system is mounted on the chassis of the shopping cart, which reshapes the shopping cart as a mobile robot. The commercialized Kinect sensor is employed to detect the gestures of the human body. The mobile shopping cart equipped with Kinect could execute different gesture command, for example, go ahead, draw back, set stop and so on. The response time is within 0.5 second. To do the right reflexes, we define a set of trajectory determined by the gesture of the target customer. The experiment result shows the validity of proposed method.