Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs

iPS細胞を用いた人工血小板の作製の効率化に成功 血小板のテイラーメイド医療に向けた一歩. 京都大学プレスリリース. 2021-12-03.Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential of universal HLA-null platelet products have stimulated research on the ex vivo differentiation of human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, and BCL-XL (MBX). imMKCLs can act as cryopreservable master cells to supply platelet concentrates. However, the proliferation rates of the imMKCLs vary with the starting hPSC clone. In this study, we reveal from the gene expression profiles of several MKCL clones that the proliferation arrest is correlated with the expression levels of specific cyclin-dependent kinase inhibitors. Silencing CDKN1A and p53 with the overexpression of MBX was effective at stably inducing imMKCLs that generate functional platelets irrespective of the hPSC clone. Collectively, this improvement in generating imMKCLs should contribute to platelet industrialization and platelet biology

W-band millimeter-wave back-scattering system for high wave number turbulence measurements in LHD

A 90 GHz W-band millimeter-wave back-scattering system is designed and installed for measuring electron scale turbulence (kρs ∼ 40). Ametal lens relay antenna is used for in-vessel beam focusing, and a beam diameter of less than 40mm is achieved in the plasma core region.This antenna can be steered at an angle of 159○ ± 6○, which almost covers the plasma radius. The estimated size of the scattering volume is ∼105mm at the edge and 135mm at the core, respectively. A 60m corrugated waveguide is used to achieve a low transmission loss of ∼8 dB. A heterodyne detection system for millimeter-wave circuits with probing power modulation can distinguish the scattered signal frombackground noise

Development and application of a ray-tracing code integrating with 3D equilibrium mapping in LHD ECH experiments

The central electron temperature has successfully reached up to 7.5 keV in large helical device(LHD) plasmas with a central high-ion temperature of 5 keV and a central electron density of1.3×1019 m−3. This result was obtained by heating with a newly-installed 154 GHz gyrotronand also the optimisation of injection geometry in electron cyclotron heating (ECH). Theoptimisation was carried out by using the ray-tracing code ‘LHDGauss’, which was upgradedto include the rapid post-processing three-dimensional (3D) equilibrium mapping obtainedfrom experiments. For ray-tracing calculations, LHDGauss can automatically read the relevantdata registered in the LHD database after a discharge, such as ECH injection settings (e.g.Gaussian beam parameters, target positions, polarisation and ECH power) and Thomsonscattering diagnostic data along with the 3D equilibrium mapping data. The equilibrium mapof the electron density and temperature profiles are then extrapolated into the region outsidethe last closed flux surface. Mode purity, or the ratio between the ordinary mode and theextraordinary mode, is obtained by calculating the 1D full-wave equation along the directionof the rays from the antenna to the absorption target point. Using the virtual magnetic fluxsurfaces, the effects of the modelled density profiles and the magnetic shear at the peripheralregion with a given polarisation are taken into account. Power deposition profiles calculatedfor each Thomson scattering measurement timing are registered in the LHD database. Theadjustment of the injection settings for the desired deposition profile from the feedbackprovided on a shot-by-shot basis resulted in an effective experimental procedure

Progress of long pulse discharges by ECH in LHD

Using ion cyclotron heating and electron cyclotron heating (ECH), or solo ECH, trials of steady state plasma sustainment have been conducted in the superconducting helical/stellarator, large helical device (LHD) (Ida K et al 2015 Nucl. Fusion 55 104018). In recent years, the ECH system has been upgraded by applying newly developed 77 and 154 GHz gyrotrons. A new gas fueling system applied to the steady state operations in the LHD realized precise feedback control of the line average electron density even when the wall condition varied during long pulse discharges. Owing to these improvements in the ECH and the gas fueling systems, a stable 39 min discharge with a line average electron density ne_ave of 1.1  ×  1019 m−3, a central electron temperature Te0 of over 2.5 keV, and a central ion temperature Ti0 of 1.0 keV was successfully performed with ~350 kW EC-waves. The parameters are much improved from the previous 65 min discharge with ne_ave of 0.15  ×  1019 m−3 and Te0 of 1.7 keV, and the 30 min discharge with ne_ave of 0.7  ×  1019 m−3 and Te0 of 1.7 keV

Controversy and consensus on the management of elevated sperm DNA fragmentation in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. Results A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians

Representative Exposure–Annoyance Relationships Due to Transportation Noises in Japan

This paper focuses on clarifying the relationship between noise exposure and the prevalence of highly annoyed people due to transportation noise in Japan. The authors accumulated 34 datasets, which were provided by Socio-Acoustic Survey Data Archive and derived from the other surveys conducted in Japan. All the datasets include the following micro-data: demographic factors, exposure, and annoyance data associated with specific noise sources. We performed secondary analyses using micro-data and established the relationships between noise exposure (Lden) and the percentage of highly annoyed people (%HA) for the following noise source: road traffic, conventional railway, Shinkansen railway, civil aircraft, and military aircraft noises. Among the five transportation noises, %HA for the military aircraft noise is the highest, followed by civil aircraft noise and Shinkansen railway noise. The %HA for conventional railway noise was higher than that for road traffic noise. To validate the representativeness of the exposure–response curves, we have discussed factors affecting the difference in annoyance. In addition, comparing the Japanese relationship with that shown in the “Environmental Noise Guidelines for the European Region,” we revealed that Japanese annoyance is higher than the WHO-reported annoyance

A Fundamental Study on Influence of Concurrently Presented Visual Stimulus Upon Loudness Perception

As a basic study on the influence of the dynamic properties of the audio-visual stimuli upon interaction between audition and vision, the effect of the simple movement involved in the visual stimulus on the loudness perception of the audio stimulus was investigated via psychophysical experiment. In this experiment, the visual stimulus given to subjects along with the audio stimulus is a bar appeared on a display, one side of which is flexibly expanding and contracting. The loudness of the audio stimulus with such a visual effect concurrently presented was rated as an absolute numerical value by using the Magnitude Estimation method. The reference of the bar length is determined so as to correspond to the Zwicker's loudness calculated for the given audio stimulus. As a result, the visual stimulus did not affect the loudness perception, when the bar was presented with its length same as the reference. On the other hand, the rating of the loudness for the same audio stimulus was significantly increased when the bar length was longer than the reference. This indicates that the change in the correspondence between the audio and the visual stimuli affect the loudness perception