Abstract
Sun-as-a-star analyses in which observational data is spatially integrated are useful for interpreting stellar data. For future applications to stellar observations, we performed ...Sun-as-a-star analyses of H
α
spectra for various active events on the Sun, not only for flares and filament eruptions/surges on the solar disk, but also for eruptions of off-limb prominences using H
α
spectral images taken by the Solar Magnetic Activity Research Telescope/Solar Dynamics Doppler Imager at Hida Observatory, Kyoto University. All the analyzed events show emission relative to the pre-event state and the changes in their H
α
equivalent widths are all on the orders of 10
−4
Å. Sun-as-a-star H
α
spectra exhibit different features depending on the causes of the emission: (i) flares show emission at the H
α
line center, together with red asymmetry and line broadening, as reported in a previous study, (ii) filament eruptions with and without flares show emission near the H
α
line center, accompanied by blueshifted/redshifted absorption; notably, the disappearance of dark filaments leads to the apparent enhancement of the H
α
line center emission, and (iii) eruptions of off-limb prominences show blueshifted/redshifted emission. These spectral features enable us to identify the active phenomena on Sun-like stars. We have also found that even the filament eruptions showing redshifted absorptions in Sun-as-a-star H
α
spectra lead to coronal mass ejections (CMEs). This result suggests that even if the falling components of stellar filament eruptions are detected as redshifted absorptions in H
α
spectra, such stellar filament eruptions may also develop into CMEs.
Current therapeutic strategies against glioblastoma multiforme (GBM) are futile mainly because of the poor access of drugs into malignant tissues, which is hindered by the tight blood-brain tumor ...barrier in the GBM vasculature. Nanomedicines have shown potential for circumventing the vascular barriers of GBM, particularly by targeting markers on the luminal side of endothelial cells in the blood vessels of GBM for achieving effective and selective translocation into the tumor. Thus, as the αvβ3 and αvβ5 integrins overexpressed on the endothelial cells of GBM can be targeted by cyclic-Arg-Gly-Asp (cRGD) peptide, herein, we developed cRGD-installed micellar nanomedicines loading epirubicin, the potent antiglioblastoma agent, through a pH-sensitive hydrazone-bond for effective treatment of GBM. These cRGD-installed epirubicin-loaded polymeric micelles (cRGD-Epi/m) achieved faster and higher penetration into U87MG cell-derived 3D-spheroids than the micelles without cRGD, conceivably through a cRGD-integrin mediated pathway. In vivo, the cRGD-installed micelles effectively suppressed the growth of an orthotopic GBM model by delivering high levels of epirubicin throughout the tumor tissue. These results indicate significant prospects for cRGD-Epi/m as an effective and translationable treatment against GBM.
cRGD-installed, epirubicin conjugated (via pH sensitive bond) polymeric micelles effectively suppressed the growth of an orthotopic GBM model by delivering high levels of epirubicin throughout the tumor tissue. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. ...However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.
Abstract
Some supernovae (SNe) are powered by the collision of the SN ejecta with dense circumstellar matter (CSM). Their emission spectra show characteristic line shapes of combined broad emission ...and narrow P Cygni lines, which should closely relate to the CSM structure and the mass-loss mechanism that creates the dense CSM. We quantitatively investigate the relationship between the line shape and the CSM structure by Monte Carlo radiative transfer simulations, considering two representative cases of dense CSM formed by steady and eruptive mass loss. Comparing the H
α
emission between the two cases, we find that a narrow P Cygni line appears in the eruptive case but does not appear in the steady case due to the difference in the velocity gradient in the dense CSM. We also reproduce the blueshifted photon excess observed in some Type IIn SNe, which is formed by photon transport across the shock wave, and find the relationship between the velocity of the shocked matter and the amount of blueshift of the photon excess. We conclude that the presence or absence of narrow P Cygni lines can distinguish the mass-loss mechanism and suggest high-resolution spectroscopic observations with
λ
/Δ
λ
≳ 10
4
after the light-curve peak for applying this diagnostic method.
Abstract
We analyze the correlation between starspots and superflares on solar-type stars using observations from the Kepler mission. The analysis shows that the observed fraction of stars with ...superflares decreases as the rotation period increases and as the amplitude of photometric variability associated with rotation decreases. We found that the fraction of stars with superflares among the stars showing large-amplitude rotational variations, which are thought to be the signature of the large starspots, also decreases as the rotation period increases. The small fraction of superflare stars among the stars with large starspots in the longer-period regime suggests that some of the stars with large starspots show a much lower flare activity than the superflare stars with the same spot area. Assuming simple relations between spot area and lifetime and between spot temperature and photospheric temperature, we compared the size distribution of large starspot groups on slowly rotating solar-type stars with that of sunspot groups. The size distribution of starspots shows the power-law distribution and the size distribution of larger sunspots lies on this power-law line. We also found that frequency–energy distributions for flares originating from spots with different sizes are the same for solar-type stars with superflares and the Sun. These results suggest that the magnetic activity we observe on solar-type stars with superflares and on the Sun is caused by the same physical processes.
Abstract
Visualization of cutaneous micro-vasculatures is a powerful approach assisting in the diagnosis of skin vascular disorders. These minute structures can be visualized by high-frequency ...ultrasound (HFUS) using ultrafast Doppler imaging. Ultrasound flow phantoms have been used as assessment tools to evaluate the performance of the ultrasound imaging system, however, to optimize the imaging system for visualization of micro-structures, flow phantom with micro-channels is required which are usually difficult to fabricate. Here, we design a simple approach for micro-flow phantom which is easy to fabricate and cast for detection of micro-circulation in superficial micro-structures. The proposed approach features (i) the micro-channels of 200-micron at the depth of 4 mm (ii) casted in the cryogel mixture of Poly-vinyl alcohol (PVA) and (iii) infused at flow speed of 30 mm/s using infusion pump. Visualization of micro-flow channel in power Doppler image obtained by HFUS ultrafast Doppler imaging reveals that the proposed micro-flow phantom could serve as a viable assessment tool for optimizing the system for in-vivo cutaneous micro-vasculature imaging.
Long-term voriconazole use may increase the risk of cutaneous squamous cell carcinoma (cSCC), especially in immunocompromised patients. However, relatively little is known regarding ...voriconazole-induced cSCC in Japan. Thus, the purpose of this study was to evaluate the association between
voriconazole use and cSCC in Japan using different national pharmacovigilance databases. First, using the Japanese Adverse Drug Event Report (JADER) database, we evaluated the association between voriconazole use and cSCC in Japan. Second, using the U. S. Food and Drug Administration Adverse
Event Reporting System (FAERS) database, we examined regional differences in the occurrence of voriconazole-induced cSCC between Japan and other countries. We calculated reporting odds ratios (RORs) as disproportionality analysis to evaluate voriconazole-induced cSCC. In this study, cases
in which one or more of "Bowen's disease", "Carcinoma in situ of skin", "Keratoacanthoma", "Squamous cell carcinoma in skin", or "Squamous cell carcinoma" were reported as adverse events were considered to be cSCC cases. The analysis based on the JADER database showed an association between
voriconazole use and cSCC in Japan, with a ROR (95% confidence interval) of 35.37 (25.60–48.87). Further, the analysis based on the FAERS database revealed that signals were detected in Japan as well as in Western countries and Australia. This study is the first in which the association
between voriconazole use and cSCC in Japan is assessed using national pharmacovigilance databases. Healthcare providers need to be fully aware of the potential for cSCC development owing to voriconazole use and in all countries, including Japan, ensure careful follow-up of patients' skin.
ABSTRACT
Small flares frequently occur in the quiet Sun. Previous studies have noted that they share many common characteristics with typical solar flares in active regions. However, their ...similarities and differences are not fully understood, especially their thermal properties. In this study, we performed imaging spectroscopic observations in the Hα line taken with the Solar Dynamics Doppler Imager on the Solar Magnetic Activity Research Telescope (SMART/SDDI) at the Hida Observatory and imaging observations with the Atmospheric Imaging Assembly onboard Solar Dynamics Observatory (SDO/AIA). We analysed 25 cases of small flares in the quiet Sun over the thermal energy range of $10^{24}{\!-\!}10^{27}\, \mathrm{erg}$ , paying particular attention to their thermal properties. Our main results are as follows: (1) We observe a redshift together with line centre brightening in the Hα line associated with more than half of the small flares. (2) We employ differential emission measure analysis using AIA multitemperature (channel) observations to obtain the emission measure and temperature of the small flares. The results are consistent with the Shibata & Yokoyama (1999, 2002) scaling law. From the scaling law, we estimated the coronal magnetic field strength of small flares to be 5–15 G. (3) The temporal evolution of the temperature and the density shows that the temperature peaks precede the density peaks in more than half of the events. These results suggest that chromospheric evaporations/condensations play an essential role in the thermal properties of some of the small flares in the quiet Sun, as does for large flares.
The ubiquitin-proteasome system is central in the regulation of cellular proteins controlling cell cycle progression and apoptosis, drawing much interest for developing effective targeted cancer ...therapies. Herein, we developed a novel pH-responsive polymeric-micelle-based carrier system to effectively deliver the proteasome inhibitor MG132 into cancer cells. MG132 is covalently bound to the block copolymer composed of polyethylene glycol (PEG) and polyaspartate through an acid-labile hydrazone bond. This bond is stable at physiological condition, but hydrolytically degradable in acidic compartments in the cell, such as late-endosomes and lysosomes, and thus, it was used for controlled release of MG132 after EPR-mediated preferential accumulation of the micelles into the tumor. MG132-loaded micelles have monodispersed size distribution with an average diameter of 45nm, and critical micelle concentration is well below 10(-7)M. In vitro studies against several cancer cell lines confirmed that MG132-loaded micelles retained the cytotoxic effect, and this activity was indeed due to the inhibition of proteasome by released MG132 from the micelles. Real-time in vitro confocal-microscopy experiments clearly indicated that MG132-conjugated micelles disintegrated only inside the target cells. By intravital confocal micro-videography, we also confirmed the prolonged circulation of MG132 loaded micelles in the bloodstream, which lead to tumor specific accumulation of micelles, as confirmed by in vivo imaging 24h after injection. These micelles showed significantly lower in vivo toxicity than free MG132, while achieving remarkable antitumor effect against a subcutaneous HeLa-luc tumor model. Our findings create a paradigm for future development of polymeric-micelle-based carrier system for other peptide aldehyde type proteasome inhibitors to make them effective cohort of the existing cancer therapeutic regiments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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