Modeling and parameter estimation of rheological objects for simultaneous reproduction of force and deformation

Abstract-Many deformable objects in our living life demonstrate rheological behaviors, such as human organs and tissues, clays and various food products. Rheological objects include both elastic and plastic properties. Due to the presence of residual (permanent) deformation, it is difficult to model rheological objects, especially to reproduce both force and residual deformation simultaneously. In this paper, a series of physical models was investigated for simulating rheological behaviors. Generalized formulations of the constitutive laws were derived for serial and parallel physical models, respectively. We found that the serial models are appropriate for formulating strain, whereas the parallel models allow a convenient calculation of stress. Analytical expressions of force and residual deformation were then derived for generalized parallel models. Theoretical discussions suggested the difficulty to reproduce both force and deformation simultaneously using linear physical models. A 2D FE (finite element) model was then formulated and an efficient method for estimating physical parameters were proposed by taking the advantages of analytical force expressions. Experimental results with commercial clay and Japanese sweets material were presented to validate our modeling and parameter estimation methods. A dual-moduli viscous element was also introduced to improve our FE model for reproducing rheological force and deformation simultaneously

Loosely Coupled Joint Driven by SMA Coil Actuators”,

Abstract-We introduce a robotic prototype of an arm with a loosely coupled joint, modeled on the human joint. A viscoelastic object functions as cartilage and soft actuators as muscles. First, we show that although viscoelastic object affords smooth movement owing to shift in the center of rotation, the repeat accuracy of the joint is poor under open-loop control. The repeat accuracy was much improved by visual feedback. Under P control, the prototype was shown to be highly robust against mechanical disturbance owing to its good mechanical compliance

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy

Population pharmacokinetic modeling of GS‐441524, the active metabolite of remdesivir, in Japanese COVID‐19 patients with renal dysfunction

腎障害患者におけるレムデシビルの薬物動態モデルを構築 --新型コロナウイルス感染症治療薬の適正使用に向けて--. 京都大学プレスリリース. 2021-11-25.Remdesivir, a prodrug of the nucleoside analog GS-441524, plays a key role in the treatment of coronavirus disease 2019 (COVID-19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID-19 with special characteristics. In this study, we aimed to measure serum GS-441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS-441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd) of GS-441524. A one-compartment model described serum GS-441524 concentration data. The CL and Vd of GS-441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS-441524 using retrospectively obtained serum GS-441524 concentrations in Japanese patients with COVID-19, which would be helpful for optimal individualized therapy of remdesivir