Railway tunnels have been constructed mainly in cold regions in South Korea recently, and damage related to freezing problems have occurred thereafter. When freezing air temperatures persist inside a tunnel, it causes damage, such as ice formation from leaks and obstruction of drainage flow. The air temperature distribution inside a tunnel is related to the area inside a tunnel, such as tunnel length, cross-section, and so forth. It can be interpreted with a convection mechanism. Tunnel length is designed depending on site conditions, and it is complicated to predict freezing air temperature distribution in a tunnel. In this study, the air temperature variation inside a long tunnel was measured in winter, and a heat transfer analysis model was implemented. A double-track railway tunnel model with a half-length ranging from 500 to 5000 m was simulated, and the conditions of freezing temperature distribution inside tunnels were investigated. The research results propose freezing conditions in railway tunnels according to tunnel lengths and minimum outside air temperatures.

IntroductionNumerous studies have suggested high concordance between tissue and circulating tumor DNA (ctDNA) comprehensive genomic profiling (CGP) tests but only few of them focused on fusions. In addition, atypical breakpoints occasionally detected from DNA-based fusion detection make interpretation difficult, and their clinical significance remains unclear. This study evaluated the clinical utility of ctDNA CGP for fusion detection.MethodsThe results of ctDNA CGP tests performed on patients with stage IV non-small cell lung cancer during routine clinical care were retrospectively reviewed. The concordance between ctDNA CGP and combined tissue test results was analyzed using CGP, immunohistochemistry, fluorescence in situ hybridization, and reverse transcription polymerase chain reaction. The clinical significance of fusions detected by ctDNA CGP, including those with atypical breakpoints at the DNA level, was assessed.ResultsIn total, 264 patients were tested with ctDNA CGP. Fusions were detected in 27 patients (10.2%), and the fusion drivers were RET (n=12, 4.6%), ALK (n=9, 3.4%), ROS1 (n=4, 1.5%), and FGFR2 (n=2, 0.8%). The overall prevalence of fusion in tissue CGP was comparable to that in ctDNA CGP. A total of 371 ctDNA-tissue test pairs were available, and the overall positive and negative percent agreement rates were 92.9% (13/14) and 100.0% (357/357), respectively. One ALK IHC-positive and ctDNA CGP-negative case did not respond to ALK-targeted therapy. Response to targeted therapy was assessed in 16 patients, and a partial response was achieved in all patients, including four with atypical breakpoints.ConclusionFusion detection using ctDNA CGP showed high concordance with tissue tests and accuracy in predicting therapeutic responses in patients with non-small cell lung cancer. ctDNA CGP may provide an important diagnostic tool for fusion detection.

본 논문에서는 운행선 터널 내 궤도 하부의 여굴 채움 방식을 평가하기 위해 음향파를 활용한 충격반향기법 시험을 수행하였다. 시험 개소는 궤도 하부에 콘크리트층으로 이루어진 A개소, 일정 두께의 콘크리트층 이후 암반층까지 자갈층으로 이루어진 B, C, D 개소를 선정하였다. 시험 결과 A개소와 다르게 궤도 하부에 자갈층이 존재하는 B, C, D 개소에서는 특정주파수에서 충격파가 공진하여 스펙트럼 밀도가 증폭되어 나타났다. 또한 최대 스펙트럼 밀도가 나타나는 주파수를 통해 이론값에 의한 궤도 하부 자갈층까지의 깊이를 산출하여 실제값과의 비교를 통해 시험의 신뢰성을 검증하였다. 본 평가 기법을 통해 운행선 터널 내 궤도 하부에 대한 명확하고 빠른 상태 평가가 가능할 것으로 판단된다.

AbstractWhole-genome sequencing is the most comprehensive form of next-generation sequencing method. We aimed to assess the additional diagnostic yield of whole-genome sequencing in patients with clinically diagnosed Charcot–Marie–Tooth disease when compared with whole-exome sequencing, which has not been reported in the literature. Whole-genome sequencing was performed on 72 families whose genetic cause of clinically diagnosed Charcot–Marie–Tooth disease was not revealed after the whole-exome sequencing and 17p12 duplication screening. Among the included families, 14 (19.4%) acquired genetic diagnoses that were compatible with their phenotypes. The most common factor that led to the additional diagnosis in the whole-genome sequencing was genotype-driven analysis (four families, 4/14), in which a wider range of genes, not limited to peripheral neuropathy-related genes, were analysed. Another four families acquired diagnosis due to the inherent advantage of whole-genome sequencing such as better coverage than the whole-exome sequencing (two families, 2/14), structural variants (one family, 1/14) and non-coding variants (one family, 1/14). In conclusion, an evident gain in diagnostic yield was obtained from whole-genome sequencing of the whole-exome sequencing-negative cases. A wide range of genes, not limited to inherited peripheral neuropathy-related genes, should be targeted during whole-genome sequencing.

Railway mountain tunnels were constructed in cold regions of Korea recently, and freezing has been generated. Most mountainous railway tunnels are designed with waterproofing membranes since groundwater exists on the backside of the tunnels. The lower air temperature inside the tunnel is transferred to the back of the tunnel lining as the outside air temperature drops below zero in winter, causing the groundwater behind the waterproofing membrane to freeze. There have been cases of freezing-related damage, such as the obstruction of drainage flow and freezing groundwater leakage. Therefore, the freezing conditions inside the tunnel should be analyzed by each tunnel length after the air temperature variation in the tunnel is measured. In this study, the air temperature inside a railway tunnel located in a cold region was measured using thermometers. The inside air temperature over time was changed by the DTR (diurnal temperature range) every 24 h. The DTR inside the tunnel was also reduced far from the entrance. Heat transfer analysis was implemented considering the air temperature variation inside the tunnel. Assuming that the minimum air temperature freezing inside the tunnel lasts seven days, the higher the minimum air temperature the longer the tunnel length. The research results show that the freezing inside a tunnel can be estimated from the tunnel length and the minimum air temperature inside the tunnel.

Background: von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by variants of the VHL tumor suppressor gene (VHL). Early detection and treatment are essential to prevent morbidity and mortality. We evaluated the effectiveness of surveillance strategies and the utility of a VHL clinic with a multidisciplinary team for the first time in Korea. Methods: The VHL clinic was organized at the Samsung Medical Center in 2011 and consisted of a multidisciplinary team, including an endocrinologist, urologist, general surgeon, neurosurgeon, ophthalmologist, otolaryngologist, and radiologist. Biochemical and imaging surveillance and personalized genetic counseling were conducted at the VHL clinic and patients were referred to the necessary departments upon detection of disease manifestation. We divided the patients in three groups (I-III) based on their compliance to VHL clinic attendance. Results: Between 2011 and 2018, 50 VHL patients were identified by VHL molecular analysis and referred to the VHL clinic. Most patients regularly participated in imaging of the central nervous system (43/50, 86.0%) and of the abdomen (46/50, 92.0%). However, there were differences in compliance to determination of the catecholamine level, audiometry, and ophthalmic examination among the three groups. Conclusions: We present the results of using a multidisciplinary team approach and showed that the VHL clinic strategy is useful for the comprehensive surveillance and management of VHL disease. We hope that VHL clinics will be widely set up in hospitals to improve prognosis in patients with VHL.

This paper presents a cooperative manipulation method for a dual-arm underwater vehicle-manipulator system (UVMS). The objective task is handle valve turning, which is a common underwater task. We propose a manipulation method that includes the concept of grasping a fixed structure such as a pipeline. While grasping a fixed structure and a handle valve, the entire system can be considered a parallel manipulator. Because of the kinematic properties of the system, the load for turning the handle valve can be distributed between the vehicle and the dual-arm manipulator, which means the vehicle can help with the operation of the manipulator. In addition, external disturbances such as oceanic currents can be efficiently compensated by using the proposed cooperative method due to the properties of the system. The kinematics and dynamics of the system were analyzed. The cooperative manipulation method was developed by modifying and adjusting redundancy resolution method with theory of a parallel manipulator. To prove the superiority of the method, a dual-arm UVMS was designed and fabricated. The advantages of the proposed cooperative method were validated through simulations and experiments.

Six-degree-of-freedom (6-DOF) hovering control is important for underwater robots to perform various tasks. Our previous underwater robot study, which used tilting thrusters, could not control 6-DOF motion simultaneously owing to several mechanical and control problems. In this study, we developed a new robot with tilting thrusters and improved 6-DOF hovering performance. The maneuverability of the robot was evaluated by analyzing the force and moment of the thrust vector. Based on this, a redundant tilting mechanism without constraints was designed to solve structural problems. A proportional–integral–derivative (PID)-based control design using the decomposition and compensation method (PID-DC) that is appropriate for this mechanism, was derived. The decomposition method was used to overcome the nonlinearity of the thrust vector caused by the tilting mechanism, and the null-space projection technique was applied to minimize the thrust force and avoid the boundary of the tilting angle. A compensator based on the empirical model of the tilting thruster transferred the control input to the system with regulation. Simulation and experimental results verified the validity of the controller for the 6-DOF hovering motion of the robot, and the hovering performance was significantly improved. Furthermore, the stability of the hovering performance under tidal currents was demonstrated through disturbance experiments.

Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disease caused by aberrations of COL3A1 which encodes type III collagen. In vEDS patients, skin hyperextensibility and joint hypermobility common in other subtypes of EDS are rarely observed, and direct sequencing has a limitation for the diagnosis of vEDS since exon deletion/duplication and splicing alterations are not uncommon in COL3A1. Such characteristic features often lead to delayed diagnosis and life-threatening complications. Here, we report two novel variants of COL3A1 diagnosed by next-generation sequencing and RNA study of cultured skin fibroblasts: an exon 27 deletion (c.1870-109_1923+10del) and a splicing variant resulting in skipping of exon 16 (c.1149+6T>C) in COL3A1. We evaluated the performance of the proposed SpliceAI for the known COL3A1 splicing variants, yielding 99.7% sensitivity. Due to the limitation of splicing prediction tools, RNA study of cultured fibroblasts either by targeted approach or whole transcriptome is necessary when vEDS is strongly suspected. If skin biopsy is not available, whole-genome sequencing could be an alternative option to RNA study.

Gitelman syndrome is a salt-losing tubular disorder that is transmitted as an autosomal recessive trait. Variants in the SLC12A3 gene are found in the majority of Gitelman syndrome patients. A 26-year-old woman visited the genetic counseling clinic. Her fiancé was a known Gitelman syndrome patient who was previously diagnosed with 2 pathogenic variants in SLC12A3. In advance of marriage and future family planning, she wanted to perform genetic testing of SLC12A3. A silent exonic variant c.1050G>A was found, and multiple splice site in silico algorithms predicted this variant to have potential alteration of splicing. This variant was classified as “variant of uncertain significance,” and RNA splicing analysis was additionally performed. RNA splicing analysis showed aberrant splicing of exon 7–8 skipping. The result points out the potential pathogenicity of this variant, which should be considered a candidate of variant reclassification in the future. We highly recommend the performance of additional RNA splicing analysis, especially for silent variants predicted to have potential alteration of splicing.

This study aimed to optimize the rope winch of a façade-cleaning robot, a system that travels vertically using the friction between ropes and pulleys. However, position errors can be caused by various factors during locomotion. This adversely affects the robot’s position accuracy. To solve this problem, an experiment was conducted to secure the repeatability of the robot position by optimizing it using the Taguchi method. Subsequently, an error compensation was designed by predicting slip errors of the rope, and accordingly the positional accuracy was determined through feedforward and feedforward + PI control. The experimental optimization confirmed that optimal repeatability can be obtained using a pressure module with the force of 45 N and an axial groove pitch angle of 6° of a pulley. The position accuracy was improved using an error prediction model based on weights, travel distances, and controllers. For a travel distance of 3.0 m, the position error could be reduced to 55%–81% and 72%–89% through feedforward control and feedforward + PI control, respectively, compared with that of the open-loop. The observations of this study could facilitate the control of the position of façade-cleaning robots and aid in the improvement of position accuracy.

Previous studies have suggested that statins can be repurposed for cancer treatment. However, the therapeutic efficacy of statins in chronic myeloid leukemia (CML) has not yet been demonstrated. In this study, we retrospectively evaluated the outcomes of 408 CML patients who underwent imatinib therapy. The deep molecular response rates in patients treated with the statin/TKI combination were significantly higher than those in patients treated with TKI alone (p = 0.0016). The statin/TKI combination exerted potent cytotoxic effects against wild-type and ABL1 mutant CML, BaF3, and K562/T315I mutant cells. Furthermore, the statin/TKI combination additively inhibited the colony-forming capacity of murine CML-KLS+ cells in vitro. In addition, we examined the additive growth-inhibitory effects of the statin/tyrosine kinase inhibitor (TKI) combination against CML patient-derived CD34+ cells. The growth-inhibitory effects of the statin/imatinib combination against CD34+/CML primary cells were higher than those against CD34+/Norm cells (p = 0.005), suggesting that the combination of rosuvastatin and imatinib exerted growth-inhibitory effects against CML CD34+ cells, but not against normal CD34+ cells. Furthermore, results from RNA sequencing of control and statin-treated cells suggested that statins inhibited c-Myc-mediated and hematopoietic cell differentiation pathways. Thus, statins can be potentially repurposed to improve treatment outcomes in CML patients when combined with TKI therapy.

Finger Clamping Unit (FCU) is a small-sized single-point clamp developed to clamp thin object of various thicknesses. It has a six-bar linkage with one compliant link, uses an electric motor as an actuator and induces toggle-lock motion by singular configuration. The main purpose of the FCU is to clamp car bodies in car assembly lines, while adapting to various thicknesses of car body. Unlike other clamping devices in the industry, it has a large clamping range (defined as the thickness range that the FCU can clamp). In this paper, the overall process of FCU development is presented. The six-bar linkage was chosen in type synthesis, and compliance was added for toggle-lock motion. Static analysis of the compliant FCU was completed, and results were plotted in a three-dimensional (3D) plot which expresses the behavior of the FCU. The lengths of each link were optimized in dimension synthesis. An FCU was constructed to reinforce the simulated results. The unique design of both the six-bar linkage FCU and the compliant link were presented. Simulated and experimental 3D plots were compared and analyzed. An appropriate friction model that best fits the experiment data was found. The advantage of the FCU-its clamping range-was proved by experiment.

The potential co-circulation of SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) could pose an unprecedented challenge to healthcare systems worldwide. Here, we compared the performance of the PowerChek SARS-CoV-2, Influenza A&B, RSV Multiplex Real-time PCR Kit (PowerChek) for simultaneous detection of SARS-CoV-2, influenza A and B, and respiratory syncytial virus with that of BioFire Respiratory Panel 2.1 (RP2.1) using 175 nasopharyngeal swab (NPS) specimens. Positive percent agreement and negative percent agreement of the PowerChek assay compared to RP2.1 were as follows: 100 % (40/40) and 100 % (135/135) for SARS-CoV-2; 100 % (39/39) and 100 % (136/136) for influenza A; 100 % (35/35) and 100 % (140/140) for influenza B; and 93.1 % (27/29) and 100 % (146/146) for RSV, respectively. The limit of detection (LOD) was accessed using RNA standards for each virus, and the LOD values of the PowerChek assay for SARS-CoV-2, influenza A and B, and RSV were 0.36, 1.24, 0.09, and 0.63 copies/μL, respectively. Our results demonstrate that the PowerChek assay is sensitive and accurate for detection of SARS-CoV-2, influenza A and B, and RSV, suggesting that this assay can be a valuable diagnostic tool when SARS-CoV-2, influenza, and RSV are co-circulating.

This study proposes a novel mechanical design of a cable-driven parallel robot (CDPR), called a dual ascender robot (DAR), which consists of two ascenders and two structures for rope-measuring sensors. Unlike other CDPRs that require external structures for winches, the DAR requires only two ropes because the traction pulleys of the ascenders allow the robot to climb on the ropes. Thus, this robot can be operated in any building. Because the ascender moves on the ropes using the friction between the rope and the traction pulley, length errors owing to rope slip are inevitable. Therefore, it is difficult to estimate the position of the robot by using the length data of the ascender. To minimize this error, a sensor-fusion method that combines the rope-length and angle-sensor data with weight factors was used. However, an optimal method of selecting the sensor resolution has not been developed yet. Therefore, this study proposes a method of selecting the sensor-reflection ratio according to sensor resolution and angle- and length-sensitivity data. The sensor-fusion method was verified to achieve excellence and resistance to rope slip through simulations and experiments. Moreover, it demonstrated improved stability of approximately 4-mm error in a 20 $\text{m}\times 20$ m space under the slip condition, compared to the position-estimation method that only used the rope-length data.

This letter proposes the use of a polygon-based random tree path planning algorithm for a variable geometry topology system (VGT). By combining a path planning algorithm and our previous non-impact locomotion algorithm, the proposed VGT system reaches an objective point. The proposed path planning algorithm provides the desired set of support polygons with a modified rapid random tree algorithm. The algorithm can significantly reduce distortion of the VGT system while moving by limiting the deformation of the desired support polygon. With this algorithm feature, constraint violations of the system were significantly reduced with respect to using a normal rapid random tree algorithm for path planning. The performance of the algorithm was validated using the simulation results.

This paper proposes a novel multi-wound differential pulley winch (MWDPW) component for assisting the ascending/descending operations of a wall climbing robot. The robotic platform enabling rope access in dangerous environments (ROPE RIDE) climbs vertical walls using a rope and embedded winch. The original winch installed on the ROPE RIDE was a single wound winch, which had problems such as rope slip, velocity ripple during descending motion, resulting the bad cleaning performance and unstable motion on the wall. These problems are mainly due to the concentration of traction force on the rope because a small portion of the winch pulley holds the entire weight of the robot. Therefore, we have developed a new winch, MWDPW, by using multi-wound differential traction pulley and pressure rollers to solve the traction force concentration problem by distributing the traction force along the entire wrapping angle. Compared to other multi-wound winches, the MWDPW has the special feature of a differential gear and pressure roller to distribute the traction force and minimize the rope slip. The tension of the MWDPW is analyzed using the basic capstan equation, and empirical results to minimize the rope slip are presented by varying design parameters such as the winding method and presence of the pressure rollers. We expect the proposed mechanism to improve the safety of a wall-climbing robot for wall-cleaning operations.

A concrete track, such as Rheda 2000 is commonly used in high-speed railways in Korea, Germany, China, etc., to enhance the operational safety of trains and to reduce the maintenance costs. However, when settlement of embankment or a crack in the concrete slab track occurs, the durability of the concrete track deteriorates significantly. Transition zones are considered to be vulnerable and are often deformed in railway embankments. The characteristics of track support stiffness and stresses on the rail in a deformed section are different from those in an undeformed section. In this study, a field measurement and numerical analysis were carried out to identify the dynamic response on transition zones where the track is deformed. A numerical analysis model was built to simulate the deformed concrete slab track, and it was compared with measured data from field tests for verification. The field tests to measure the stresses on the rail were performed in a train speed range from 280 to 300 km/h. According to the numerical analysis, the dynamic characteristics of the track varied with train speeds, which were then compared with the allowable stresses of the concrete slab track.