Examination of High-Torque Sandwich-Type Spherical Ultrasonic Motor Using with High-Power Multimode Annular Vibrating Stator

Spherical ultrasonic motors (SUSMs) that can operate with multiple degrees of freedom (MDOF) using only a single stator have high holding torque and high torque at low speed, which makes reduction gearing unnecessary. The simple structure of MDOF-SUSMs makes them useful as compact actuators, but their development is still insufficient for applications such as joints of humanoid robots and other systems that require MDOF and high torque. To increase the torque of a sandwich-type MDOF-SUSM, we have not only made the vibrating stator and spherical rotor larger but also improved the structure using three design concepts: (1) increasing the strength of all three vibration modes using multilayered piezoelectric actuators (MPAs) embedded in the stator, (2) enhancing the rigidity of the friction driving portion of the stator for transmitting more vibration force to the friction-driven rotor surface, and (3) making the support mechanism more stable. An MDOF-SUSM prototype was tested, and the maximum torques of rotation around the X(Y)-axis and Z-axis were measured as 1.48 N?m and 2.05 N?m, respectively. Moreover, the values for torque per unit weight of the stator were obtained as 0.87 N?m/kg for the X(Y)-axis and 1.20 N?m/kg for the Z-axis. These are larger than values reported for any other sandwich-type MDOF-SUSM of which we are aware. Hence, the new design concepts were shown to be effective for increasing torque. In addition, we measured the transient response and calculated the load characteristics of rotation around the rotor’s three orthogonal axes

A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β1 pathways

Renal fibrosis is closely related to chronic inflammation and is under the control of epigenetic regulations. Because the signaling of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) play key roles in progression of renal fibrosis, dual blockade of TGF-β1 and TNF-α is desired as its therapeutic approach. Here we screened small molecules showing anti-TNF-α activity in the compound library of indole derivatives. 11 out of 41 indole derivatives inhibited the TNF-α effect. Among them, Mitochonic Acid 35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent effect. The anti-TNF-α activity was mediated by inhibiting IκB kinase phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in the mice. Additionally, MA-35 concurrently showed an anti-TGF-β1 effect by inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-β1-induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney, which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis with the downregulation of inflammatory cytokines and fibrotic gene expressions. Furthermore, MA-35 inhibited TGF-β1-induced H3K4me1 histone modification of the fibrotic gene promoter, leading to a decrease in the fibrotic gene expression. MA-35 affects multiple signaling pathways involved in the fibrosis and may recover epigenetic modification; therefore, it could possibly be a novel therapeutic drug for fibrosis

Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial

Examination of High-Torque Sandwich-Type Spherical Ultrasonic Motor Using with High-Power Multimode Annular Vibrating Stator

Spherical ultrasonic motors (SUSMs) that can operate with multiple degrees of freedom (MDOF) using only a single stator have high holding torque and high torque at low speed, which makes reduction gearing unnecessary. The simple structure of MDOF-SUSMs makes them useful as compact actuators, but their development is still insufficient for applications such as joints of humanoid robots and other systems that require MDOF and high torque. To increase the torque of a sandwich-type MDOF-SUSM, we have not only made the vibrating stator and spherical rotor larger but also improved the structure using three design concepts: (1) increasing the strength of all three vibration modes using multilayered piezoelectric actuators (MPAs) embedded in the stator, (2) enhancing the rigidity of the friction driving portion of the stator for transmitting more vibration force to the friction-driven rotor surface, and (3) making the support mechanism more stable. An MDOF-SUSM prototype was tested, and the maximum torques of rotation around the X(Y)-axis and Z-axis were measured as 1.48 N∙m and 2.05 N∙m, respectively. Moreover, the values for torque per unit weight of the stator were obtained as 0.87 N∙m/kg for the X(Y)-axis and 1.20 N∙m/kg for the Z-axis. These are larger than values reported for any other sandwich-type MDOF-SUSM of which we are aware. Hence, the new design concepts were shown to be effective for increasing torque. In addition, we measured the transient response and calculated the load characteristics of rotation around the rotor’s three orthogonal axes

Traditional Japanese Medicine Daikenchuto Improves Functional Constipation in Poststroke Patients

Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P<0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P<0.01, P=0.049, and P=0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P=0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393)