KUS121 attenuates the progression of monosodium iodoacetate-induced osteoarthritis in rats

Currently there is no effective treatment available for osteoarthritis (OA). We have recently developed Kyoto University Substances (KUSs), ATPase inhibitors specific for valosin-containing protein (VCP), as a novel class of medicine for cellular protection. KUSs suppressed intracellular ATP depletion, endoplasmic reticulum (ER) stress, and cell death. In this study, we investigated the effects of KUS121 on chondrocyte cell death. In cultured chondrocytes differentiated from ATDC5 cells, KUS121 suppressed the decline in ATP levels and apoptotic cell death under stress conditions induced by TNFα. KUS121 ameliorated TNFα-induced reduction of gene expression in chondrocytes, such as Sox9 and Col2α. KUS121 also suppressed ER stress and cell death in chondrocytes under tunicamycin load. Furthermore, intraperitoneal administration of KUS121 in vivo suppressed chondrocyte loss and proteoglycan reduction in knee joints of a monosodium iodoacetate-induced OA rat model. Moreover, intra-articular administration of KUS121 more prominently reduced the apoptosis of the affected chondrocytes. These results demonstrate that KUS121 protects chondrocytes from stress-induced cell death in vitro and in vivo, and indicate that KUS121 is a promising novel therapeutic agent to prevent the progression of OA

Interhemispheric asymmetry of the high‐latitude ionospheric convection on 11–12 May 1999

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95394/1/jgra16830.pd

Estimates of foil thickness, signal, noise, and nuclear heating of imaging bolometers for ITER

Imaging bolometers have been studied for ITER to serve as a complementary diagnostic to the resistive bolometers for the measurement of radiated power. Two tangentially viewing InfraRed imaging Video Bolometers (IRVB) could be proposed for an ITER equatorial port, one having a view of the entire plasma cross-section (core viewing) and one tilted down 43 degrees from the horizontal to view the divertor (divertor viewing). The IRVBs have 7 cm (horizontal) by 9 cm (vertical) Pt sensor foils, 6 mm × 6 mm apertures, 15 × 20 pixels and focal lengths of 7.8 cm and 21 cm, respectively. Using SANCO and SOLPS models for a 840 m3 plasma radiating 67.3 MW, synthetic images from the IRVBs are calculated to estimate the maximum signal strengths to be 246 W/m2 and 62 W/m2, respectively. We propagate the X-ray energy spectra from the models through the synthetic diagnostics to give the photon energy spectrum for each IRVB pixel, which are used to calculate the fraction of the power absorbed by the foil as a function of foil thickness. Using a criteria of >95% absorbed power fraction, we selected foil thicknesses of 30 μm and 10 μm, respectively. We used these thicknesses and assumed IR systems having 105 fps, 1024×1280 pixels and sensitivities of 15 mK, to calculate the IRVB sensitivities of 3.19 W/m2 and 1.05 W/m2, and signal to noise ratios of 77 and 59, respectively. Using the Monte Carlo Nuclear Particle code we calculated for the core viewing IRVB the foil heating by neutrons to be 1.0 W/m2 and by gammas to be 117 W/m2. This indicates that countermeasures may be needed to remove the nuclear heating signal

Global diagnostics of ionospheric absorption during X-ray solar flares based on 8-20MHz noise measured by over-the-horizon radars

An analysis of noise attenuation during eighty solar flares between 2013 and 2017 was carried out at frequencies 8-20 MHz using thirty-four SuperDARN radars and the EKB ISTP SB RAS radar. The attenuation was determined on the basis of noise measurements performed by the radars during the intervals between transmitting periods. The location of the primary contributing ground sources of noise was found by consideration of the propagation paths of radar backscatter from the ground. The elevation angle for the ground echoes was determined through a new empirical model. It was used to determine the paths of the noise and the location of its source. The method was particularly well suited for daytime situations which had to be limited for the most part to only two crossings through the D region. Knowing the radio path was used to determine an equivalent vertical propagation attenuation factor. The change in the noise during solar flares was correlated with solar radiation lines measured by GOES/XRS, GOES/EUVS, SDO/AIA, SDO/EVE, SOHO/SEM and PROBA2/LYRA instruments. Radiation in the 1 to 8$\mathring{A}$ and and near 100$\mathring{A}$ are shown to be primarily responsible for the increase in the radionoise absorption, and by inference, for an increase in the D and E region density. The data are also shown to be consistent with a radar frequency dependence having a power law with an exponent of -1.6. This study shows that a new dataset can be made available to study D and E region.Comment: 30 pages, 5 figures, 2 tables. Submitted to Space Weathe

Search for solar axions in XMASS, a large liquid-xenon detector

XMASS, a low-background, large liquid-xenon detector, was used to search for solar axions that would be produced by bremsstrahlung and Compton effects in the Sun. With an exposure of 5.6ton days of liquid xenon, the model-independent limit on the coupling for mass $\ll$ 1keV is $|g_{aee}|< 5.4\times 10^{-11}$ (90% C.L.), which is a factor of two stronger than the existing experimental limit. The bounds on the axion masses for the DFSZ and KSVZ axion models are 1.9 and 250eV, respectively. In the mass range of 10-40keV, this study produced the most stringent limit, which is better than that previously derived from astrophysical arguments regarding the Sun to date

A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis

京大開発の薬剤「KUS121」の変形性膝関節症への効果を確認 --外傷性変形性関節症の治療薬として臨床応用へ--. 京都大学プレスリリース. 2020-12-17.Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA