Patients with systemic lupus erythematosus have abnormally elevated Epstein–Barr virus load in blood

Various genetic and environmental factors appear to be involved in systemic lupus erythematosus (SLE). Epstein–Barr virus (EBV) is among the environmental factors that are suspected of predisposing to SLE, based on the characteristics of EBV itself and on sequence homologies between autoantigens and EBV antigens. In addition, higher titers of anti-EBV antibodies and increased EBV seroconversion rates have been observed in SLE patients as compared with healthy control individuals. Serologic responses do not directly reflect EBV status within the body. Clarification of the precise status of EBV infection in SLE patients would help to improve our understanding of the role played by EBV in this disease. In the present study we determined EBV types in SLE patients (n = 66) and normal control individual (n = 63) by direct PCR analysis of mouthwash samples. We also compared EBV load in blood between SLE patients (n = 24) and healthy control individuals (n = 29) using semiquantitative PCR assay. The number of infections and EBV type distribution were similar between adult SLE patients and healthy control individuals (98.5% versus 94%). Interestingly, the EBV burden in peripheral blood mononuclear cells (PBMCs) was over 15-fold greater in SLE patients than in healthy control individuals (mean ± standard deviation: 463 ± 570 EBV genome copies/3 μg PBMC DNA versus 30 ± 29 EBV genome copies/3 μg PBMC DNA; P = 0.001), suggesting that EBV infection is abnormally regulated in SLE. The abnormally increased proportion of EBV-infected B cells in the SLE patients may contribute to enhanced autoantibody production in this disease

Design of User motion intention algorithm for improving accuracy for Active upper limb exercise Robot

In this paper, an algorithm for recognizing the user’s intention by utilizing single channel electromyogram sensor and force sensor is proposed as a method for generating a synchronization signal of an active-type upper limb motion robot. In active-type upper limb motion robot system, a physical human-robot interface device physically connects users with the robot, and the motion of the user is recognized and delivered to the robot by the interface device in order to provide the necessary physical force to the user. By using the force sensor that is built inside the interface device, the intention of the user’s motion is recognized. Although the sensor is capable of measuring the magnitude of force, it is unable to distinguish between the force applied by the exterior and the external force generated by the user. Moreover, in case of the electromyogram signal, it is only expressed when the user actually generates the force, whereas its exact magnitude cannot be measured. Therefore, the suggested algorithm includes a step for each of the following: filtering the signal extracted from the electromyogram sensor, determining the recognition of the user’s motion after the filtering, classifying the signal expressed by the force sensor on the orthogonal coordinate space in accordance with the user’s motion, and outputting the user’s motion intention signal by converting the classified signal into a signal, related with the force and torque. In other words, the algorithm lets the user’s motion intention signal measured by the force sensor to be output only when the user’s motion is recognized as the electromyogram signal. According to the suggested method— which relies on eliminating the signals that are output, except for the motions generated by the user—the reliability of the user motion intention signal delivered to the robot can be enhanced

Optimal cutoff of pretreatment neutrophil-to-lymphocyte ratio in head and neck cancer patients: a meta-analysis and validation study

Abstract Background The prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups. Methods We performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540). Results Pretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66–2.31) and DFS (HR = 1.90, 95%CI = 1.41–2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses. Conclusions Meta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics

Development of Optical System for ARGO-M

ARGO-M is a satellite laser ranging (SLR) system developed by the Korea Astronomy and Space Science Institute with the consideration of mobility and daytime and nighttime satellite observation. The ARGO-M optical system consists of 40 cm receiving telescope, 10 cm transmitting telescope, and detecting optics. For the development of ARGO-M optical system, the structural analysis was performed with regard to the optics and optomechanics design and the optical components. To ensure the optical performance, the quality was tested at the level of parts using the laser interferometer and ultra-high-precision measuring instruments. The assembly and alignment of ARGO-M optical system were conducted at an auto-collimation facility. As the transmission and reception are separated in the ARGO-M optical system, the pointing alignment between the transmitting telescope and receiving telescope is critical for precise target pointing. Thus, the alignment using the ground target and the radiant point observation of transmitting laser beam was carried out, and the lines of sight for the two telescopes were aligned within the required pointing precision. This paper describes the design, structural analysis, manufacture and assembly of parts, and entire process related with the alignment for the ARGO-M optical system

Diethylstilbestrol, a Novel ANO1 Inhibitor, Exerts an Anticancer Effect on Non-Small Cell Lung Cancer via Inhibition of ANO1

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related mortality; thus, therapeutic targets continue to be developed. Anoctamin1 (ANO1), a novel drug target considered for the treatment of NSCLC, is a Ca2+-activated chloride channel (CaCC) overexpressed in various carcinomas. It plays an important role in the development of cancer; however, the role of ANO1 in NSCLC is unclear. In this study, diethylstilbestrol (DES) was identified as a selective ANO1 inhibitor using high-throughput screening. We found that DES inhibited yellow fluorescent protein (YFP) fluorescence reduction caused by ANO1 activation but did not inhibit cystic fibrosis transmembrane conductance regulator channel activity or P2Y activation-related cytosolic Ca2+ levels. Additionally, electrophysiological analyses showed that DES significantly reduced ANO1 channel activity, but it more potently reduced ANO1 protein levels. DES also inhibited the viability and migration of PC9 cells via the reduction in ANO1, phospho-ERK1/2, and phospho-EGFR levels. Moreover, DES induced apoptosis by increasing caspase-3 activity and PARP-1 cleavage in PC9 cells, but it did not affect the viability of hepatocytes. These results suggest that ANO1 is a crucial target in the treatment of NSCLC, and DES may be developed as a potential anti-NSCLC therapeutic agent

Impaired Reelin-Dab1 Signaling Contributes to Neuronal Migration Deficits of Tuberous Sclerosis Complex

SummaryTuberous sclerosis complex (TSC) is associated with neurodevelopmental abnormalities, including defects in neuronal migration. However, the alterations in cell signaling mechanisms critical for migration and final positioning of neurons in TSC remain unclear. Our detailed cellular analyses reveal that reduced Tsc2 in newborn neurons causes abnormalities in leading processes of migrating neurons, accompanied by significantly delayed migration. Importantly, we demonstrate that Reelin-Dab1 signaling is aberrantly regulated in TSC mouse models and in cortical tubers from TSC patients owing to enhanced expression of the E3 ubiquitin ligase Cul5, a known mediator of pDab1 ubiquitination. Likewise, mTORC1 activation by Rheb overexpression generates similar neuronal and Reelin-Dab1 signaling defects, and directly upregulates Cul5 expression. Inhibition of mTORC1 by rapamycin treatment or by reducing Cul5 largely restores normal leading processes and positioning of migrating neurons. Thus, disrupted Reelin-Dab1 signaling is critically involved in the neuronal migration defects of TSC