Radiotherapy is a well-established treatment for cancer. However, the existence of radioresistant cells is one of the major obstacles in radiotherapy. In order to understand the mechanism of cellular ...radioresistance and develop more effective radiotherapy, we have established clinically relevant radioresistant (CRR) cell lines, which continue to proliferate under daily exposure to 2 Gray (Gy) of X-rays for >30 days. X-ray irradiation significantly induced autophagic cells in parental cells, which was exiguous in CRR cells, suggesting that autophagic cell death is involved in cellular radiosensitivity. An autophagy inducer, rapamycin sensitized CRR cells to the level of parental cells and suppressed cell growth. An autophagy inhibitor, 3-methyladenine induced radioresistance of parental cells. Furthermore, inhibition of autophagy by knockdown of Beclin-1 made parental cells radioresistant to acute radiation. These suggest that the suppression of autophagic cell death but not apoptosis is mainly involved in cellular radioresistance. Therefore, the enhancement of autophagy may have a considerable impact on the treatment of radioresistant tumor.
A new timing detector measuring ∼50MeV/c positrons is under development for the MEG II experiment, aiming at a time resolution σt∼30ps. The resolution is expected to be achieved by measuring each ...positron time with multiple counters made of plastic scintillator readout by silicon photomultipliers (SiPMs). The purpose of this work is to demonstrate the time resolution for ∼50MeV/c positrons using prototype counters. Counters with dimensions of 90×40×5mm3 readout by six SiPMs (three on each 40×5mm2 plane) were built with SiPMs from Hamamatsu Photonics and AdvanSiD and tested in a positron beam at the DAΦNE Beam Test Facility. The time resolution was found to improve nearly as the square root of the number of counter hits. A time resolution σt=26.2±1.3ps was obtained with eight counters with Hamamatsu SiPMs. These results suggest that the design resolution is achievable in the MEG II experiment.
Abstract Klotho mutant mice, defective in the klotho gene, develop multiple age-related disorders with very short lifespans. Introduction of the exogenous klotho gene into these mutant mice leads to ...an improvement in their phenotypes, while overexpression of this gene in wild-type mice significantly extends their lifespan. These observations suggest that the klotho gene/protein has an anti-aging function. Since there have been only a few reports with some disagreement about results on the CNS of the mutant mice, we tried to clarify whether the CNS neurons generate aging-like features, even in premature stages, using biochemical and morphological approaches. Results obtained from the mutant mice, when compared with wild-type mice, were as follows. Neurofilaments (NFs) were increased significantly in axons, with the subunit proteins showing a significant enhancement in phosphorylation or expression of NF-H or NF-L, respectively. Microtubules in Purkinje cell dendrites were closer to each other, and in the CNS tissue tubulin was unaltered, but microtubule-associated protein (MAP) 2 was significantly reduced in expression. Neuronal cellular organelles were morphologically disordered. Lysosomes, cathepsin D and light chain 3 of MAP1A/B (LC3) were augmented with the appearance of putative autophagy-related structures. Antiapoptotic Bcl-xL and proapoptotic Bax were reduced and enhanced, respectively, and mitogen-activated protein kinase was reduced. Synapse-related proteins and structures were decreased. Neuronal degeneration was evident in hippocampal pyramidal cells, and possibly in Purkinje cells. Astrocytic glial filaments and glial fibrillary acidic protein were increased in density and expression, respectively. Together, the CNS neuronal alterations in klotho mutant mice were quite similar to those found in aged animals, including even premature death, so this mouse should be a more appropriate animal model for CNS aging than those previously reported.
Abstract
The Regional Oceanic Modeling System (ROMS) is applied in a nested configuration with realistic forcing to the Southern California Bight (SCB) to analyze the variability in semidiurnal ...internal wave generation and propagation. The SCB has a complex topography with supercritical slopes that generate linear internal waves at the forcing frequency. The model predicts the observed barotropic and baroclinic tides reasonably well, although the observed baroclinic tides feature slightly larger amplitudes. The strongest semidiurnal barotropic to baroclinic energy conversion occurs on a steep sill slope of the 1900-m-deep Santa Cruz Basin. This causes a forced, near-resonant, semidiurnal Poincaré wave that rotates clockwise in the basin and is of the first mode along the radial, azimuthal, and vertical directions. The associated tidal-mean, depth-integrated energy fluxes and isotherm oscillation amplitudes in the basin reach maximum values of about 5 kW m−1 and 100 m and are strongly modulated by the spring–neap cycle. Most energy is locally dissipated, and only 10% escapes the basin. The baroclinic energy in the remaining basins is orders of magnitudes smaller. High-resolution coastal models are important in locating overlooked mixing hotspots such as the Santa Cruz Basin. These mixing hotspots may be important for ocean mixing and the overturning circulation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The MEG II experiment, based at the Paul Scherrer Institut in Switzerland, reports the result of a search for the decay
μ
+
→
e
+
γ
from data taken in the first physics run in 2021. No excess of ...events over the expected background is observed, yielding an upper limit on the branching ratio of
B
(
μ
+
→
e
+
γ
)
<
7.5
×
10
-
13
(90% CL). The combination of this result and the limit obtained by MEG gives
B
(
μ
+
→
e
+
γ
)
<
3.1
×
10
-
13
(90% CL), which is the most stringent limit to date. A ten-fold larger sample of data is being collected during the years 2022–2023, and data-taking will continue in the coming years.
No direct observational evidence of sprite‐produced active radicals has been presented owing to the difficulty of observing a small event area in the nighttime mesosphere, whereas sprite chemical ...models have indicated that sprite discharge locally affects the atmospheric composition. We present the first observational evidence of a HO2 production above sprite‐producing thunderstorms from the coincidence of temporal‐spatial observations of HO2 spectra, sprite events, and thunderstorms by two space instruments, a submillimeter‐wave limb spectrometer and ultraviolet/visible Imager and a ground‐based very low frequency radiation lightning detection network. A total of three areas was identified with enhanced HO2 levels of approximately 1025 molecules. A chemical sprite model indicates an increase in HO2 in the considered altitude region; however, the predicted production due to a single sprite event is smaller than the observed enhancement. Our observational results suggest that sprites potentially contribute 1% of nighttime background HO2 generation at altitudes of 75–80 km globally.
We report on gamma-ray observations of the supernova remnant (SNR) RX J0852.0--4622 with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope. In the Fermi-LAT data, we find a ...spatially extended source at the location of the SNR. The extension is consistent with the SNR size seen in other wavelengths such as X-rays and TeV gamma rays, leading to the identification of the gamma-ray source with the SNR. The spectrum is well described as a power law with a photon index of Delta *G = 1.85 ? 0.06 (stat)+0.18 -- 0.19 (sys), which smoothly connects to the H.E.S.S. spectrum in the TeV energy band. We discuss the gamma-ray emission mechanism based on multiwavelength data. The broadband data can be fit well by a model in which the gamma rays are of hadronic origin. We also consider a scenario with inverse Compton scattering of electrons as the emission mechanism of the gamma rays. Although the leptonic model predicts a harder spectrum in the Fermi-LAT energy range, the model can fit the data considering the statistical and systematic errors.
This paper discusses the effects of radiation damage to SiPMs on the performances of plastic scintillator counters with series-connected SiPM readout, focusing on timing measurements. The ...performances of a counter composed of a 120×40×5mm3 scintillator tile read out by two sets of six SiPMs from AdvanSiD connected in series attached on the short sides are presented, for different combinations of SiPMs at various levels of irradiation. Firstly, six SiPMs were equally irradiated with electrons from 90Sr sources up to a fluence of Φe−≈3×1012cm−2. The timing resolution of the counter gradually deteriorated by the increase in dark current. The dark current and the deterioration were reduced when the counter was cooled from 30 °C to 10 °C. Secondly, 33 SiPMs were irradiated with reactor neutrons. The fluence levels ranged from Φeq≈8.7×108cm−2 to Φeq≈5.5×1013cm−2. The characteristics of counters read out by series-connected SiPMs with non-uniform damage levels were investigated. The signal pulse height, the time response, and the timing resolution depend on the hit position in the counter when SiPMs’ irradiation is not uniform.
In the last decade, the molecular mechanisms of apoptosis, a major type of active cell death (type I cell death) have largely been clarified in mammalian cells. Particularly, the caspase family of ...proteinases has been shown to play crucial roles in the execution of apoptosis. Differing from apoptosis, type II cell death is known to be associated with autophagosomes/autolysosomes and appear in the developing nervous system (CLARKE, 1990). We have previously shown that delayed neuronal death occurring in the CA1 pyramidal layer of the gerbil hippocampus after brief forebrain ischemia is apoptotic in nature and autophagosomes/autolysosomes abundantly appear in the neurons before DNA fragmentation. To further understand the roles of autophagosomes/autolysosomes in active cell death, we examined the apoptosis of PC12 cells using morphological and biochemical techniques. PC12 cells are known to undergo apoptosis when cultured in the absence of serum. In such an environment, the mitochondrial pathway of apoptosis is activated; cytochrome c is released from mitochondria, and caspase-9/caspase-3 are activated. We have first examined morphological features of PC12 cells during the apoptotic process following serum deprivation, and found that autophagy is induced from the early stage of the process in the cells before typical nuclear changes. When autophagy is inhibited in the cells by 3-methyladenine, an autophagy inhibitor, they are largely protected from apoptosis. In relation to the induction of autophagy in PC12 cells following serum deprivation, immunoreactivity, protein amounts, and the proteolytic activity of lysosomal proteinases, particularly cathepsins B and D, are all greatly altered; those of cathepsin B drastically decrease in the cells from the early stage of serum-deprived cultures, whereas those of cathepsin D increase. Moreover, PC12 cells overex-pressing cathepsin D undergo apoptosis more rapidly in serum-deprived cultures than wild-type cells, whereas those overexpressing cathepsin B increase the viability. These lines of evidence suggest that autophagy is involved in PC12 cell death following serum deprivation, this type of cell death being regulated by lysosomal proteinases, cathepsins B and D, downstream autophagy.
We present observations of HESS J1640–465 with the Fermi-Large Area Telescope. The source is detected with high confidence as an emitter of high-energy gamma-rays. The spectrum lacks any evidence for ...the characteristic cutoff associated with emission from pulsars, indicating that the emission arises primarily from the pulsar wind nebula (PWN). Broadband modeling implies an evolved nebula with a low magnetic field resulting in a high γ-ray to X-ray flux ratio. The Fermi emission exceeds predictions of the broadband model, and has a steeper spectrum, possibly resulting from a distinct excess of low energy electrons similar to what is inferred for both the Vela X and Crab PWNe.
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