Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
Summary Objective The objectives were to investigate the in vivo effects of treatment with rebamipide on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA) ...and to explore its mode of action. Materials and methods OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA). Oral administration of rebamipide was initiated on the day of MIA injection, 3 or 7 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), hypoxia-inducible factor-2α (HIF-2α), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription–polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes. Results Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1β, HIF-2α, iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1β-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3. Conclusion The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.
Nitrogen dioxide (NO2) columns observed from space have been useful in detecting the increase of nitrogen oxides (NOx) emissions in East Asia, particularly China, coinciding with rapid economic ...growth during the past several decades. NO2 columns retrieved above a particular location reflect a combination of local NOx emissions and transported NOx from upwind sources. In this study, we demonstrate the transport of NOx emitted in East Asia using satellite and surface in situ measurements and Lagrangian particle dispersion model simulations. Enhanced satellite NO2 columns in the Yellow Sea (between China and South Korea) and the East Sea (between South Korea and Japan), and different seasonal variations of NO2 in China, North and South Korea, and Japan, suggest the importance of NOx transport in understanding the local NOx budget. Lagrangian transport model simulations with tracers of different chemical lifetimes identify source‐receptor relationships that explain high NO2 over the oceans and springtime peaks in Korea and Japan, with China being the most likely source region. Our results have important implications for studies using satellite NO2 retrievals to derive NOx emissions at local scales in regions adjacent to large sources, such as in East Asia, Europe, and the Eastern U.S.
Key Points
Satellite demonstrates springtime transport of NOx over Korea and Japan
Transport from China explains large NO2 columns over the Yellow Sea
Transport of NOx is important in understanding local budget of NOx
Context. Feedback from active galactic nuclei (AGN) is thought to play an important role in quenching star formation in galaxies. However, the efficiency with which AGN dissipate their radiative ...energy into the ambient medium remains strongly debated. Aims. Enormous observational efforts have been made to constrain the energetics of AGN feedback by mapping the kinematics of the ionized gas on kpc scale. We study how the observed kinematics and inferred energetics are affected by beam smearing of a bright unresolved narrow-line region (NLR) due to seeing. Methods. We re-analyse optical integral-field spectroscopy of a sample of twelve luminous unobscured quasi-stellar objects (QSOs) (0.4 <z< 0.7) previously presented in the literature. The point-spread function (PSF) for the observations is directly obtained from the light distribution of the broad Hbeta line component. Therefore, we are able to compare the ionized gas kinematics and derived energetics of the total, truly spatially extended, and unresolved Oiii emission. Results. We find that the spatially resolved Oiii line width on kpc scales is significantly narrower than the one before PSF deblending. The extended NLRs (ENLRs) appear intrinsically offset from the QSO position or more elongated which can be interpreted in favour of a conical outflow on large scales while a spherical geometry cannot be ruled out for the unresolved NLR. We find that the kinetic power at 5 kpc distance based on a spherical model is reduced by two orders of magnitude for a conical outflow and one order of magnitude for the unresolved NLR after PSF deblending. This reduced kinetic power corresponds to only 0.01-0.1 per cent of the bolometric AGN luminosity. This is smaller than the 5-10% feedback efficiency required by some cosmological simulations to reproduce the massive galaxy population. The injected momentum fluxes are close or below the simple radiation-pressure limit L sub(bol)/c for the conical outflow model for the NLR and ENLR when beam smearing is considered. Conclusions. Integral-field spectroscopy is a powerful tool to investigate the energetics of AGN outflows, but the impact of beam smearing has to be taken into account in the high contrast regime of QSOs. For the majority of observations in the literature, this has not been addressed carefully so that the incidence and energetics of presumed kpc-scale AGN-driven outflows still remain an unsolved issue, from an observational perspective.
We use the high-resolution simulation MassiveBlackII to examine scaling relations between black hole (BH) mass and host galaxy properties (σ, total M
* and L
V
), finding good agreement with recent ...observational data, especially at the high-mass end. We find Gaussian intrinsic scatter (∼half the observed scatter) about all three relations, except among the most massive objects. Below z ∼ 2 the slope of the relations remain roughly z-independent, and only steepen by 50 per cent by z ∼ 4. The normalization of the σ, L
V
relations evolve by 0.3, 0.43 dex, while the M
* correlation does not evolve out to at least z ∼ 2. Testing for selection biases, we find M
BH- or M
*-selected samples have steeper slopes than random samples, suggesting a constant-mass selection function can exhibit faster evolution than a random sample. We find a potential bias among high-L
BH subsamples due to their more massive hosts, but that bright (active) active galactic nuclei exhibit no intrinsic bias relative to fainter (inactive) BHs in equivalent-mass hosts. Finally, we show that BHs below the local relation tend to grow faster than their host (72 per cent of BHs >0.3 dex below the mean relation have an M
BH–M
* trajectory steeper than the local relation), while those above have shallower trajectories (only 14 per cent are steeper than local). Thus BHs tend to grow faster than their hosts until surpassing the local relation, when their growth is suppressed, bringing them back towards the mean relation.
Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the ...prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.
An inventory of air pollutant emissions in Asia in the year 2000 is developed to support atmospheric modeling and analysis of observations taken during the TRACE‐P experiment funded by the National ...Aeronautics and Space Administration (NASA) and the ACE‐Asia experiment funded by the National Science Foundation (NSF) and the National Oceanic and Atmospheric Administration (NOAA). Emissions are estimated for all major anthropogenic sources, including biomass burning, in 64 regions of Asia. We estimate total Asian emissions as follows: 34.3 Tg SO2, 26.8 Tg NOx, 9870 Tg CO2, 279 Tg CO, 107 Tg CH4, 52.2 Tg NMVOC, 2.54 Tg black carbon (BC), 10.4 Tg organic carbon (OC), and 27.5 Tg NH3. In addition, NMVOC are speciated into 19 subcategories according to functional groups and reactivity. Thus we are able to identify the major source regions and types for many of the significant gaseous and particle emissions that influence pollutant concentrations in the vicinity of the TRACE‐P and ACE‐Asia field measurements. Emissions in China dominate the signature of pollutant concentrations in this region, so special emphasis has been placed on the development of emission estimates for China. China's emissions are determined to be as follows: 20.4 Tg SO2, 11.4 Tg NOx, 3820 Tg CO2, 116 Tg CO, 38.4 Tg CH4, 17.4 Tg NMVOC, 1.05 Tg BC, 3.4 Tg OC, and 13.6 Tg NH3. Emissions are gridded at a variety of spatial resolutions from 1° × 1° to 30 s × 30 s, using the exact locations of large point sources and surrogate GIS distributions of urban and rural population, road networks, landcover, ship lanes, etc. The gridded emission estimates have been used as inputs to atmospheric simulation models and have proven to be generally robust in comparison with field observations, though there is reason to think that emissions of CO and possibly BC may be underestimated. Monthly emission estimates for China are developed for each species to aid TRACE‐P and ACE‐Asia data interpretation. During the observation period of March/April, emissions are roughly at their average values (one twelfth of annual). Uncertainties in the emission estimates, measured as 95% confidence intervals, range from a low of ±16% for SO2 to a high of ±450% for OC.
Estimates of biomass burning in Asia are developed to facilitate the modeling of Asian and global air quality. A survey of national, regional, and international publications on biomass burning is ...conducted to yield consensus estimates of “typical” (i.e., non‐year‐specific) estimates of open burning (excluding biofuels). We conclude that 730 Tg of biomass are burned in a typical year from both anthropogenic and natural causes. Forest burning comprises 45% of the total, the burning of crop residues in the field comprises 34%, and 20% comes from the burning of grassland and savanna. China contributes 25% of the total, India 18%, Indonesia 13%, and Myanmar 8%. Regionally, forest burning in Southeast Asia dominates. National, annual totals are converted to daily and monthly estimates at 1° × 1° spatial resolution using distributions based on AVHRR fire counts for 1999–2000. Several adjustment schemes are applied to correct for the deficiencies of AVHRR data, including the use of moving averages, normalization, TOMS Aerosol Index, and masks for dust, clouds, landcover, and other fire sources. Good agreement between the national estimates of biomass burning and adjusted fire counts is obtained (R2 = 0.71–0.78). Biomass burning amounts are converted to atmospheric emissions, yielding the following estimates: 0.37 Tg of SO2, 2.8 Tg of NOx, 1100 Tg of CO2, 67 Tg of CO, 3.1 Tg of CH4, 12 Tg of NMVOC, 0.45 Tg of BC, 3.3 Tg of OC, and 0.92 Tg of NH3. Uncertainties in the emission estimates, measured as 95% confidence intervals, range from a low of ±65% for CO2 emissions in Japan to a high of ±700% for BC emissions in India.
Aim
To evaluate the neurosensory outcome of management of damaged inferior alveolar nerves caused by endodontic overfilling and to assess the efficacy of delayed surgical intervention.
Methodology
...Nine patients who underwent surgical removal of extruded endodontic material were included. All patients were evaluated for neurosensory function using a set of standardized tests. The outcome of surgical intervention was evaluated through patient interview and quantitative statistical analysis.
Results
Surgical procedures included foreign body removal, microsurgical external/internal decompression, excision of neuroma followed by nerve repair, and excision of damaged nerve segment with interpositional nerve graft. Seven of the nine patients had significant improvement according to the follow‐up neurosensory assessment. Four patients reported significant improvement, three patients reported mild improvement and two patients reported no appreciable improvement in the Visual Analog Scale (VAS). Two patients who reported no appreciable improvement in VAS also did not achieve FSR. In these patients, calcium hydroxide was spread widely along the IAN and a surgical approach was obtained via sagittal spit osteotomy. The mean time to reach FSR was 222.7 (±41.8) days with a range of 106–397 days. In the early repair group who received surgery within 60 days, three out of five patients achieved FSR in a mean time of 198.0 (±76.2) days. The mean time to FSR in all four subjects who received surgical attention over 60 days after injury was 241.3 (±139.8) days with a range of 106–397 days. As all four cases in the late repair group with limited amount of nerve injury achieved FSR, only 3 of 5 early repair cases with wide‐spread injury achieved a similar outcome.
Conclusion
The results of this case series confirmed the notion that surgical management of the inferior alveolar nerve is effective in the treatment of nerve injuries caused by endodontic extrusion of calcium hydroxide paste. Delayed surgical repair of the inferior alveolar nerve can be indicated and helpful for the neurosensory recovery of damaged IAN, however, the surgical management was less effective in case of widespread nerve injuries.
Discovery of two dimensional (2D) magnets, showing intrinsic ferromagnetic (FM) or antiferromagnetic (AFM) orders, has accelerated development of novel 2D spintronics, in which all the key components ...are made of van der Waals (vdW) materials and their heterostructures. High-performing and energy-efficient spin functionalities have been proposed, often relying on current-driven manipulation and detection of the spin states. In this regard, metallic vdW magnets are expected to have several advantages over the widely-studied insulating counterparts, but have not been much explored due to the lack of suitable materials. Here, we report tunable itinerant ferro- and antiferromagnetism in Co-doped Fe
GeTe
utilizing the vdW interlayer coupling, extremely sensitive to the material composition. This leads to high T
antiferromagnetism of T
~ 226 K in a bulk and ~210 K in 8 nm-thick nanoflakes, together with tunable magnetic anisotropy. The resulting spin configurations and orientations are sensitively controlled by doping, magnetic field, and thickness, which are effectively read out by electrical conduction. These findings manifest strong merits of metallic vdW magnets as an active component of vdW spintronic applications.
PDF
