Tactile display for presenting stiffness distribution using magnetorheological fluid

This paper describes a tactile display for reproducing stiffness distributions based on magnetorheological (MR) fluid. This display can represent stiffness distribution by controlling the applied magnetic field locally. Computed tomography (CT) and endoscopy are currently used to diagnosis intravital conditions. However, CT cannot detect tumors smaller than 5 mm, and endoscopy can only diagnosis the tissue surface. Since tumors are stiffer than normal tissue, endoscopic palpation may be effective for detecting tumors smaller than 5 mm located beneath the tissue surface. To perform such palpation, a tactile display that can reproduce the spatial stiffness distribution of tissue is strongly required. For intravital tissue, the display must be capable of creating stiffness values ranging from about 200 to about 600 kPa with a spatial resolution of less than 5 mm. In the present study, a tactile display is proposed that exploits the ability of a MR fluid to change its stiffness in a magnetic field. In the proposed device, the MR fluid is encapsulated in an acrylic chamber covered by a thin flexible membrane. We first characterized the mechanical properties of the device and then, conducted sensory experiments with five subjects to verify that the device could display stiffness distribution. The magnetic field was produced by a cylindrical permanent magnet with a diameter of 5 mm, and the applied field strength was controlled by varying the separation between the magnet and the display. The experimental results indicated that the proposed display could successfully recreate the stiffness distribution including stiffness of tumor tissue under a local magnetic field of 200 mT. The device was then evaluated using five subjects, who were asked to touch the device with their index fingers and estimate the size of the stiff spot. Although the results varied among subjects, all were capable of perceiving spots smaller than 5mm

Differential scanning fluorimetric analysis of the amino-acid binding to taste receptor using a model receptor protein, the ligand-binding domain of fish T1r2a/T1r3

Taste receptor type 1 (T1r) is responsible for the perception of essential nutrients, such as sugars and amino acids, and evoking sweet and umami (savory) taste sensations. T1r receptors recognize many of the taste substances at their extracellular ligand-binding domains (LBDs). In order to detect a wide array of taste substances in the environment, T1r receptors often possess broad ligand specificities. However, the entire ranges of chemical spaces and their binding characteristics to any T1rLBDs have not been extensively analyzed. In this study, we exploited the differential scanning fluorimetry (DSF) to medaka T1r2a/T1r3LBD, a current sole T1rLBD heterodimer amenable for recombinant preparation, and analyzed their thermal stabilization by adding various amino acids. The assay showed that the agonist amino acids induced thermal stabilization and shifted the melting temperatures (T-m) of the protein. An agreement between the DSF results and the previous biophysical assay was observed, suggesting that DSF can detect ligand binding at the orthostericbinding site in T1r2a/T1r3LBD. The assay further demonstrated that most of the tested Lamino acids, but no D-amino acid, induced T-m shifts of T1r2a/T1r3LBD, indicating the broad L-amino acid specificities of the proteins probably with several different manners of recognition. The T-m shifts by each amino acid also showed a fair correlation with the responses exhibited by the full-length receptor, verifying the broad amino-acid binding profiles at the orthosteric site in LBD observed by DSF

Dynamic Characteristics of a Hydraulic Amplification Mechanism for Large Displacement Actuators Systems

We have developed a hydraulic displacement amplification mechanism (HDAM) and studied its dynamic response when combined with a piezoelectric actuator. The HDAM consists of an incompressible fluid sealed in a microcavity by two largely deformable polydimethylsiloxane (PDMS) membranes. The geometry with input and output surfaces having different cross-sectional areas creates amplification. By combining the HDAM with micro-actuators, we can amplify the input displacement generated by the actuators, which is useful for applications requiring large deformation, such as tactile displays. We achieved a mechanism offering up to 18-fold displacement amplification for static actuation and 12-fold for 55 Hz dynamic actuation

Clinical Significance of Septal Malalignment for Transcatheter Closure of Atrial Septal Defect

Background. Septal malalignment is related to erosion and device embolization in transcatheter closure of atrial septal defect (ASD), but limited information is available. Objectives. This study aimed to assess clinical significance of septal malalignment and to determine appropriate evaluation of ASD diameter, including the selection of device size. Methods. Four hundred and seventeen patients with ASD who underwent transcatheter closure were enrolled. Septal malalignment was defined as separation between the septum primum and the septum secundum on transesophageal echocardiography. Results. One hundred and eighty-four patients had septal malalignment. The frequency of septal malalignment increased with age reaching around 50% in adult patients. Septal malalignment was related to aortic rim deficiency. The distance of separation between the septum primum and the septum secundum was 5 +/- 2 mm (range, 1-11 mm). In patients with septal malalignment, the ASD diameter measured at the septum primum was 19 +/- 6 mm, while the ASD diameter measured at the septum secundum was 16 +/- 6 mm. There was a difference of 4 +/- 2 mm (range, 0-8 mm) between the ASD diameter measured at the septum primum and that measured at the septum secundum. For transcatheter closure, the Amplatzer Septal Occluder device size 2-3 mm larger and the Occlutech Figulla Flex II device size 4-7 mm larger than the ASD diameter measured at the septum primum were frequently used. During the study period, erosion or device embolization did not occur in all of the patients. Conclusions. Septal malalignment is highly prevalent in adult patients with aortic rim deficiency. The measurement of ASD diameter at the septum primum can be valuable for the selection of device size in patients with septal malalignment

N -Ethyl- N -Nitrosourea Induces Retinal Photoreceptor Damage in Adult Rats

Seven-week-old male Lewis rats received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was evaluated 7 days after the treatment. Sequential morphological features of the retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone H2A.X (γ-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR) expression in response to DNA damage of the retina. All rats that received ≥ 400 mg/kg of ENU developed retinal degeneration characterized by the loss of photoreceptor cells in both the central and peripheral retina within 7 days. In the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the photoreceptor cells and peaked 24 hr after ENU treatment. The γ-H2AX signals in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment, and the PAR signals selectively located in the photoreceptor cell nuclei appeared at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was restricted to photoreceptor cells, and no degenerative changes in inner retinal cells were seen at any time points. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after ENU treatment. In conclusion, ENU induced retinal degeneration in adult rats that was characterized by photoreceptor cell apoptosis through PARP activity

Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche

Masahiko Yamaguchi, Yoko Watanabe, Takuji Ohtani, Akiyoshi Uezumi, Norihisa Mikami, Miki Nakamura, Takahiko Sato, Masahito Ikawa, Mikio Hoshino, Kunihiro Tsuchida, Yuko Miyagoe-Suzuki, Kazutake Tsujikawa, Shin’ichi Takeda, Hiroshi Yamamoto, So-ichiro Fukada, Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche, Cell Reports, Volume 13, Issue 2, 2015, Pages 302-314, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2015.08.083

ERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes

ヒトのiPS細胞から新生児レベルまで成熟した心筋細胞を作製する. 京都大学プレスリリース. 2021-06-21.Lowering the cost of heart cell therapies. 京都大学プレスリリース. 2021-06-21.One of the earliest maturation steps in cardiomyocytes (CMs) is the sarcomere protein isoform switch between TNNI1 and TNNI3 (fetal and neonatal/adult troponin I). Here, we generate human induced pluripotent stem cells (hiPSCs) carrying a TNNI1[EmGFP] and TNNI3[mCherry] double reporter to monitor and isolate mature sub-populations during cardiac differentiation. Extensive drug screening identifies two compounds, an estrogen-related receptor gamma (ERRγ) agonist and an S-phase kinase-associated protein 2 inhibitor, that enhances cardiac maturation and a significant change to TNNI3 expression. Expression, morphological, functional, and molecular analyses indicate that hiPSC-CMs treated with the ERRγ agonist show a larger cell size, longer sarcomere length, the presence of transverse tubules, and enhanced metabolic function and contractile and electrical properties. Here, we show that ERRγ-treated hiPSC-CMs have a mature cellular property consistent with neonatal CMs and are useful for disease modeling and regenerative medicine

Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.</p