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As automated driving has not yet been established, on narrow roads where there is no separation between pedestrians and vehicles, it is essential to switch to manual driving. However, when the driver turns the steering wheel from one hand to another on narrow roads, it causes steering burdens and operational errors if the steering feel or burden is not proper. Thus, this study aims to construct an active steering wheel system that provides an appropriate steering feel or burden by controlling the steering reaction torque, driving position and steering gear ratio for each driver. In this paper, we focused on and examined the driving position among these. A two-dimensional steering model that considers the size of the arms for each driver was established to evaluate steering burden. In addition, a basic study was conducted on the appropriate driving position. Then, based on the joint movements and angles calculation, the appropriate driving position that considers the size of the arms was studied by evaluating the joint power. As a result, it was found that if the steering wheel position is too close to the driver, the amount of joint movement increases, and if it is too far away, the joint movement decreases. Therefore, it was found that the appropriate steering wheel position for each driver’s arm length can be considered by using the joint power.

Mechanical vibrations adversely affect mechanical components, and in the worst case, lead to serious accidents by breaking themselves. To suppress vibrations, various studies have been conducted on vibration isolation, suppression, and resistance. In addition, technologies to actively suppress vibration have been rapidly developed in recent years, and it has been reported that vibrations can be suppressed with higher performance. However, these studies have been conducted mostly for low-order systems, and few studies have employed control models that consider the complex vibration characteristics of multi-degree-of-freedom (DOF) systems. This study is a basic study that establishes a control model for complex control systems, and the vibration characteristics of a 2-DOF system are calculated using the vibration analysis of a multi-DOF system. Furthermore, the vibration suppression performance of the 2-DOF system is investigated by performing vibration experiments.

The yaw acceleration required for circuit driving is determined by the time variation of the yaw rate due to two factors: corner radius and velocity at the center of gravity. Torque vectoring systems have the advantage where the yaw moment can be changed only by the longitudinal force without changing the lateral force of the tires, which greatly affects lateral acceleration. This is expected to improve the both the spinning performance and the orbital performance, which are usually in a trade-off relationship. In this study, we proposed a yaw moment control technology that actively utilized a power unit with a brake system, which was easy to implement in a system, and compared the performance of vehicles equipped with and without the proposed system using the Milliken Research Associates moment method for quasi-steady-state analysis. The performances of lateral acceleration and yaw moment were verified using the same method, and a variable corner radius simulation for circuit driving was used to compare time and performance. The results showed the effectiveness of the proposed system.

Flexible steel plates are generally transported by rollers; however, the contact between the rollers and the steel plate degrades the surface quality of the plate. To solve this problem, noncontact transportation of steel plates using electromagnetic force has been proposed. However, ultrathin flexible steel plates can easily fall owing to deflection. A magnetic levitation system using electromagnets installed in the horizontal direction has also been proposed to improve the levitation performance of a conventional system. However, it is difficult to control vibrations with such a system because flexible steel plates are elastically deformed into complex shapes by gravity. Therefore, an electromagnetic levitation system was proposed, wherein electromagnets were installed near the edge of the steel plate such that it could be controlled with noncontact grip, such as by allowing one side of the steel plate to hang. This system is expected to improve levitation stability because the moment of inertia increases with vertical levitation and simplifies the control system. In addition, this system actively uses gravity acting on a steel plate to decrease its deflection. The use of gravity to suppress deflection is novel. In this study, the feasibility of magnetic levitation using the proposed system was investigated using magnetic field analysis. Its usefulness was investigated experimentally using a constructed magnetic levitation system. In addition, it was found that a magnetic levitation system that maintains the standing position generates a peculiar vibration.

The deterioration of ride comfort in ultra-compact vehicles has recently become an increasing concern. Active seat suspension was proposed to improve the ride comfort of ultra-compact vehicles. An active seat suspension is a vibration control device that is easily installed. The general vibration control system of the active seat suspension is fed back to the displacement and velocity by integrating the measured seat acceleration. This control has problems, such as control delay and deviation by integration. In this study, we focused on vibration control using acceleration directly. First, we established a control model that feeds back the acceleration to terminate the error occurring in the integral process and investigated the change in vibration characteristics in the case where the feedback gain of acceleration was changed. Second, the control system was analyzed to investigate the performance of the control based on the frequency characteristics. As a result, it was confirmed that the frequency response changes when the feedback gain is changed. In acceleration feedback control, ride comfort was improved by selecting a proper feedback gain because the characteristics of frequency were changed by the gain.

Recently, research on non-contact conveyance systems using electromagnetic levitation technology has accelerated. We have constructed an electromagnetic levitation control system that keeps the relative distance between the electromagnet and steel plate constant. To investigate the levitation stability of thin steel plates, we performed magnetic levitation experiments on a thin steel plate with curvature. A physical disturbance was applied to the electromagnet units by vibrators. The electromagnet units were vibrated up and down by a vibrator. We investigated whether the bending magnetic levitation improved the levitation performance even if the magnetic levitation system was in a vibrating environment. We determined that it was possible to realize stable levitation for a steel plate under external disturbances during levitation at the optimal bending angle.

SLE is a systemic multi-organ autoimmune condition associated with reduced life expectancy and quality of life. Glucocorticoids (GC) are heavily relied on for SLE treatment but are associated with detrimental metabolic effects. Type 1 interferons (IFN) are central to SLE pathogenesis and may confer GC insensitivity. Glucocorticoid-induced leucine zipper (GILZ) mediates many effects of GC relevant to SLE pathogenesis, but the effect of IFN on GC regulation of GILZ is unknown. We performed in vitro experiments using human PBMC to examine the effect of IFN on GILZ expression. JAK inhibitors tofacitinib and tosylate salt were used in vivo and in vitro respectively to investigate JAK-STAT pathway dependence of our observations. ChiP was performed to examine glucocorticoid receptor (GR) binding at the GILZ locus. Several public data sets were mined for correlating clinical data. High IFN was associated with suppressed GILZ and reduced GILZ relevant to GC exposure in a large SLE population. IFN directly reduced GILZ expression and suppressed the induction of GILZ by GC in vitro in human leukocytes. IFN actions on GILZ expression were dependent on the JAK1/Tyk2 pathway, as evidenced by loss of the inhibitory effect of IFN on GILZ in the presence of JAK inhibitors. Activation of this pathway led to reduced GR binding in key regulatory regions of the GILZ locus. IFN directly suppresses GILZ expression and GILZ upregulation by GC, indicating a potential mechanism for IFN-induced GC resistance. This work has important implications for the ongoing development of targeted GC-sparing therapeutics in SLE.

Mutations in ryanodine receptor 1 (RyR1), a Ca2+ release channel in skeletal muscle, cause malignant hyperthermia (MH) and are involved in heat stroke. Here, the authors show that an oxolinic acid-derivative RyR1 inhibitor effectively prevents and treats MH and heat stroke in various MH mouse models.

Abstract Climatic change will affect elevational vegetation distribution because vegetation distribution is related to thermal conditions. However, how elevational species distributions are determined by biotic and abiotic factors is not clear. The long‐term plot census along an elevational gradient is indispensable to clarify mechanisms of elevational distribution of tree species. Two congeneric conifers, the less shade‐tolerant Abies veitchii and shade‐tolerant A. mariesii, dominate at low and high elevations, respectively, in the subalpine zone in Japan. This study investigated the population dynamics of the two species at three elevations (low, middle, high) for 13 years to examine why the two species dominated the different elevations from the viewpoints of competition and disturbance. This study showed that growth and survival rates were not highest at the most dominant elevations for each species. At the high elevation where A. mariesii dominated and small disturbances frequently occurred, the recruitment rate of A. mariesii was highest among the three elevations and that of A. veitchii was largely decreased by tree competition. However, A. veitchii was dominant earlier than A. mariesii at the low elevation after large disturbances by the high growth rate of individual trees. Therefore, A. mariesii was superior to A. veitchii at the high elevation because of its high recruitment rate and large reduction of recruitment of A. veitchii due to competition, while A. veitchii was superior to A. mariesii at the low elevation after large disturbances because of higher growth rate than A. mariesii. It is suggested that the elevational distributions of the two species were determined by elevational changes in population dynamics in relation to competition and disturbance. Long‐term observational studies of forest dynamics among various elevations are indispensable to predict the effects of climatic change on vegetation distribution.

Providing a comfortable sound for users is an important factor for high-value products. Therefore, many studies have investigated pleasant sound levels for developing and manufacturing new products. Notably, sounds containing 1/f fluctuations provide a relaxing effect in humans. There are many studies on the influence of sound signals, including 1/f fluctuations; however, the verification of fluctuations, including sound signals, has not been performed. In this study on fluctuation, the discrete Fourier transform was used to directly calculate the time of the sound signal. We evaluated the duration of music and the 1/f fluctuation via the discrete Fourier transform using the time history of the music data. Furthermore, we investigated the relaxation effect of music containing a 1/f fluctuation. We determined a person’s comfort according to the difference in the calculated fluctuation coefficient by subjectively evaluating the comfort felt by people when listening to music with two different fluctuation coefficients, and we examined the improvement in the fluctuation coefficient and human comfort.

We investigated whether there is a correlation between the comfort felt by occupants and the comfort estimated from biological information obtained by experiments to improve the ride quality of an ultra-compact vehicle. A single frequency in the vertical direction can help to estimate occupant comfort. However, we hypothesized that the study of a single frequency was insufficient. We oscillated the occupants with vibrations containing multiple vibration frequencies and obtained biometric information. The vibration frequency was set based on the difference in ride quality felt by humans. Biometric information was obtained using a cerebral hemodynamic meter and electrocardiogram. Acquiring multiple types of biometric information helps to more accurately estimate the psychological state. After the experiment, we obtained a subjective evaluation of comfort against vibrations using the visual analog scale (VAS). The biometric information obtained by the experiment was cluster-analyzed, and experimental participants with similar characteristics of the biometric information were grouped. Multiple regression analysis was performed based on the values of the typical biometric information of the cluster. Comfort was estimated from biometric information using multiple regression analysis. A correlation was confirmed between measured and estimated VAS scores.

A hybrid vehicle is a vehicle with two or more power sources. We propose a hybrid system in which the engine torque converted by the transmission is combined with an electric motor torque. The proposed system reduces transmission because engine torque only acts during transmission. Furthermore, the proposed hybrid system’s simple structure uses lightweight chains and sprockets that can be laid out in various ways. The realization of the proposed hybrid system requires independent control algorithms for the two power systems, engine and electric motor, that take into consideration the state of the vehicle and the driver’s input; this system can be assumed to be a servo model system with multiple inputs and outputs and analyzed to obtain the optimal operation algorithm. To apply these controls to race cars, which are required to be fast, it is necessary to obtain the reference input, which is the optimal velocity and yaw angle while traveling the course of the servo system, and simulations of the competition track must be carried out. Therefore, the dynamic performance of the hybrid system was investigated by calculating the lap times on a given circuit using a quasi-steady-state method with low computational load and high prediction accuracy. In this study, the effects of changing the electric motor and final gear ratios on the driving performance of a rear-wheel-drive parallel hybrid system for optimization were investigated. The simulation results show that not only can the optimum settings be obtained by changing the final and electric motor reduction ratios on the evaluation circuit, but also that the optimum values vary across different speed ranges on different circuits.

Abstract Background MicroRNAs (miRNAs) are involved in the regulation of key biological processes and have been implicated in various diseases, including autoimmune disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is considered to be mediated by autoimmune reactions. To determine miRNA role in the development and progression of PM and DM, we performed plasma miRNA profiling in PM/DM patients before and after treatment. Methods Total RNA was isolated from plasma of 10 patients before and after treatment with prednisolone, or, in case of prednisolone resistance or complications, with the combination of calcineurin inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide. The expression of miRNAs was determined using miRNA microarray and validated by qRT-PCR. Results More differentially expressed miRNAs were found in plasma of DM patients compared to PM patients before and after treatment, and their profiles were different. Among the differentially expressed plasma miRNA identified by microarray, the levels of hsa-miR-4442 were confirmed by qRT-PCR to be significantly decreased by treatment. In addition, plasma hsa-miR-4442 content in active PM/DM significantly exceeded that in other active autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as in healthy individuals. The level of plasma hsa-miR-4442 was positively correlated with Skeletal Disease Activity in MITAX (Myositis Intention to Treat Activity Index). Conclusion This is the first report describing plasma miRNA expression profiles in PM/DM patients. The present data suggest that plasma levels of miRNAs may be associated with polymyositis/dermatomyositis and hsa-miR-4442 could be used as a biomarker for PM/DM diagnosis and/or disease activity.

We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro. Cell proliferation was evaluated by cell count and immunoblotting. The expression of IGF-1 and IGF-1 R was evaluated by RT-PCR. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase staining, a bone resorption assay, and osteoclast-specific enzyme production. Angiogenesis was evaluated by a tube formation assay using human umbilical vein endothelial cells (HUVECs). The proliferation of MH7A cells was found to be inhibited in the presence of NVP-AEW541, and the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt was downregulated in MH7A cells. IGF-1 and IGF-1 R mRNA expression levels were upregulated during formation of M-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL)-mediated osteoclast formation. Moreover, osteoclastogenesis was suppressed in the presence of NVP-AEW541. The formation of the tubular network was enhanced by IGF-1, and this effect was neutralized by NVP-ARE541. Our findings suggest that NVP-AEW541 may be utilized as a potential therapeutic agent in the treatment of RA.

Levitation improvement of the bending levitation performance of thin steel plate was performed. First, the point of the steel plate where the vibration is predominantly generated was estimated using an ultrathin steel plate with a thickness of 0.18 mm. Furthermore, to decrease the vibration, levitation experiments by means of changing the bending shape and using permanent magnets were performed and the standard deviation of the displacement and levitation probability were evaluated. In addition, to determine the effect of the permanent magnets, the shape of the steel plate was analyzed using the finite difference method. As a result, the main vibration generating area was confirmed to be the longitudinal central edge area of the steel plate. In order to suppress the vibration in this area, the vibration of the steel plate was decreased by making an asymmetrical bending shape. Also, the vibration of the steel plate was suppressed by placing the permanent magnets in the positions that matched with the results of the analysis.

A 57-year-old Japanese man was admitted to the hospital with back pain and fever, multiple lung nodules, and abdominal aortic aneurysm (AAA). Laboratory tests performed at admission showed an increased proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) level. Video-associated thoracoscopic lung biopsy was performed; pathologic examination showed granulation tissue with necrosis and multinucleated giant cells. The diagnosis of granulomatosis with polyangiitis (GPA) was confirmed on the basis of the clinical presentation, laboratory findings, and lung biopsy. All symptoms were ameliorated, and the serum level of PR3-ANCA declined following treatment with prednisolone and cyclophosphamide. Although the association of GPA with AAA is rare, GPA may be included among the large vessel vasculitides that can give rise to aortic aneurysm.

MicroRNA (miRNA) is small RNA of 20 to 22 nucleotides in length and is stably present in plasma. Regulating the expression of miRNA taken into cells has been suggested as a general therapeutic approach. We identified the novel anti-inflammatory miRNA hsa-miR-766-3p and investigated its biological function in human rheumatoid arthritis (RA) fibroblast-like synoviocyte MH7A cells. To verify the function of the miRNA present in the plasma of RA patients, we performed a comprehensive analysis of the miRNA expression during abatacept treatment and identified eight miRNAs with significantly altered expression levels. Among these eight miRNAs, miR-766-3p was found to have a clear function. The expression of inflammatory genes in response to inflammatory stimuli was suppressed in MH7A transduced with miR-766-3p. We showed that miR-766-3p indirectly reduced the activation of NF-κB and clarified that this mechanism was partially involved in the reduction of the mineralocorticoid receptor expression. In addition, the inflammatory responses were suppressed in other types of cells. These results indicate the novel function of miR-766-3p, findings that may aid in the development of therapies to suppress inflammation, not only in RA but also in other diseases.

Active seat suspension has been proposed to improve ride comfort for ultra-compact mobility. Regarding the ride comfort of passengers due to vertical vibration, the authors have confirmed from biometry measurements that reduction of the vibration acceleration does not always produce the best ride comfort for passengers. Therefore, heart rate variability that can quantitatively reflect stress is measured in real time, and a control method was proposed that feeds back to active suspension and confirms its effectiveness by fundamental verification. In this paper, we will confirm the influence of the vibration stress on the psychological state of the occupant by the masking method.

With recent advances in technologies such as those of semiconductors and actuators, easy-to-control compact actuators have been actively applied in various fields such as factory automation and precision machining. In the automobile industry, major manufacturers and venture companies are also concentrating on electric vehicle development. Ultra-compact mobility vehicles, which exhibit an excellent environmental performance and are highly convenient for short-distance movement, are becoming popular. However, owing to cabin space limitations, it is difficult to mount systems such as power steering for assisting steering operations, and such systems are currently not installed in most ultra-compact mobility vehicles. Our research group focused on a steer-by-wire system that does not require a physical connection between the steering wheel and the wheels. Using this system, the steering wheel can be installed without any constraints, and the cabin layout can be easily changed. The reaction torque applied to the steering wheel can be expected to provide an optimum steering feel to each driver by controlling the reaction-force-generating actuator output. Drivers with different heights and arm lengths were then grouped, and arm model calculation and electromyogram measurements obtained during steering operations were used to examine the muscle burden experienced during driving owing to differences in the drivers’ physiques.

In non-clinical toxicity studies of orally dosed small molecule drugs, methyl cellulose (MC) is commonly used as the vehicle. It is well tolerated and easy to prepare. However, it is not suitable as the vehicle for all poorly soluble compounds. The objective of this study was to evaluate the noobserved-effect levels (NOELs) of solvents that are possible alternative vehicles for 2-week oral administration of poorly soluble drugs. Five animals/group were dosed once daily with 25 mg/kg/day MC 400 (0.5% MC, control group), up to 5,000 mg/kg/day of polyethylene glycol 400 (PEG 400), 5,500 mg/kg/day of dimethyl sulfoxide (DMSO), 1,000 mg/kg/day of hydroxypropyl-β-cyclodextrin (HP-ß-CD), 250 mg/kg/day of polysorbate 80 (Tween 80), 600 mg/kg/day of sodium dodecyl sulfate (SDS), 9,000 mg/kg/day of olive oil and sesame oil, and 600 mg/kg/day of lactic acid. Parameters evaluated included clinical signs, clinical pathology, organ weight, gross pathology, and histopathology. The NOELs were considered to be 1,250 mg/kg/day for PEG 400, 1,000 mg/kg/day for HP-β-CD, 250 mg/kg/day for Tween 80, 4,500 mg/kg/day for olive oil, 4,500 mg/kg/day for sesame oil, and 600 mg/kg/day for lactic acid. The NOELs of DMSO and SDS could not be determined, because rats dosed with DMSO or SDS showed DMSO-specific offensive odor or SDS-related significant irritant effects even at the lowest dose levels (DMSO, 1,100 mg/kg/day; SDS, 150 mg/kg/day). This study provides the NOELs of several solvents that could be used as vehicles in 2-week oral toxicity studies in rats. [ABSTRACT FROM AUTHOR]

SLE is a systemic multi-organ autoimmune condition associated with reduced life expectancy and quality of life. Glucocorticoids (GC) are heavily relied on for SLE treatment but are associated with detrimental metabolic effects. Type 1 interferons (IFN) are central to SLE pathogenesis and may confer GC insensitivity. Glucocorticoid-induced leucine zipper (GILZ) mediates many effects of GC relevant to SLE pathogenesis, but the effect of IFN on GC regulation of GILZ is unknown. We performed in vitro experiments using human PBMC to examine the effect of IFN on GILZ expression. JAK inhibitors tofacitinib and tosylate salt were used in vivo and in vitro respectively to investigate JAK-STAT pathway dependence of our observations. ChiP was performed to examine glucocorticoid receptor (GR) binding at the GILZ locus. Several public data sets were mined for correlating clinical data. High IFN was associated with suppressed GILZ and reduced GILZ relevant to GC exposure in a large SLE population. IFN directly reduced GILZ expression and suppressed the induction of GILZ by GC in vitro in human leukocytes. IFN actions on GILZ expression were dependent on the JAK1/Tyk2 pathway, as evidenced by loss of the inhibitory effect of IFN on GILZ in the presence of JAK inhibitors. Activation of this pathway led to reduced GR binding in key regulatory regions of the GILZ locus. IFN directly suppresses GILZ expression and GILZ upregulation by GC, indicating a potential mechanism for IFNinduced GC resistance. This work has important implications for the ongoing development of targeted GC-sparing therapeutics in SLE. [ABSTRACT FROM AUTHOR]