Black carbon (BC) particles over the Himalayas and Tibetan Plateau (HTP), both airborne and those deposited on snow, have been shown to affect snowmelt and glacier retreat. Since BC over the HTP may ...originate from a variety of geographical regions and emission sectors, it is essential to quantify the source-receptor relationships of BC in order to understand the contributions of natural and anthropogenic emissions and provide guidance for potential mitigation actions. In this study, we use the Community Atmosphere Model version 5 (CAM5) with a newly developed source-tagging technique, nudged towards the MERRA meteorological reanalysis, to characterize the fate of BC particles emitted from various geographical regions and sectors. Evaluated against observations over the HTP and surrounding regions, the model simulation shows a good agreement in the seasonal variation in the near-surface airborne BC concentrations, providing confidence to use this modeling framework for characterizing BC source-receptor relationships. Our analysis shows that the relative contributions from different geographical regions and source sectors depend on season and location in the HTP. The largest contribution to annual mean BC burden and surface deposition in the entire HTP region is from biofuel and biomass (BB) emissions in South Asia, followed by fossil fuel (FF) emissions from South Asia, then FF from East Asia. The same roles hold for all the seasonal means except for the summer, when East Asia FF becomes more important. For finer receptor regions of interest, South Asia BB and FF have the largest impact on BC in the Himalayas and central Tibetan Plateau, while East Asia FF and BB contribute the most to the northeast plateau in all seasons and southeast plateau in the summer. Central Asia and Middle East FF emissions have relatively more important contributions to BC reaching the northwest plateau, especially in the summer. Although local emissions only contribute about 10% of BC in the HTP, this contribution is extremely sensitive to local emission changes. Lastly, we show that the annual mean radiative forcing (0.42 W m-2) due to BC in snow outweighs the BC dimming effect (-0.3 W m-2) at the surface over the HTP. We also find strong seasonal and spatial variation with a peak value of 5 W m-2 in the spring over the northwest plateau. Such a large forcing of BC in snow is sufficient to cause earlier snow melting and potentially contribute to the acceleration of glacier retreat.
Integration of electrochemical capacitors with silicon-based electronics is a major challenge, limiting energy storage on a chip. We describe a wafer-scale process for manufacturing strongly adhering ...carbide-derived carbon films and interdigitated micro-supercapacitors with embedded titanium carbide current collectors, fully compatible with current microfabrication and silicon-based device technology. Capacitance of those films reaches 410 farads per cubic centimeter/200 millifarads per square centimeter in aqueous electrolyte and 170 farads per cubic centimeter/85 millifarads per square centimeter in organic electrolyte. We also demonstrate preparation of self-supported, mechanically stable, micrometer-thick porous carbon films with a Young's modulus of 14.5 gigapascals, with the possibility of further transfer onto flexible substrates. These materials are interesting for applications in structural energy storage, tribology, and gas separation.
Context. Ultraviolet bursts are transients in the solar atmosphere with an increased impulsive emission in the extreme UV lasting for one to several tens of minutes. They often show spectral profiles ...indicative of a bi-directional outflow in response to magnetic reconnection. Aims. To understand UV bursts, we study how motions of magnetic elements at the surface can drive the self-consistent formation of a current sheet resulting in plasmoid-mediated reconnection. In particular, we want to study the role of the height of the reconnection in the atmosphere. Methods. We conducted numerical experiments solving the 2D magnetohydrodynamic equations from the solar surface to the upper atmosphere. Motivated by observations, we drove a small magnetic patch embedded in a larger system of magnetic field of opposite polarity. This type of configuration creates an X-type neutral point in the initial potential field. The models are characterized by the (average) plasma-β at the height of this X point. Results. The driving at the surface stretches the X-point into a thin current sheet, where plasmoids appear, accelerating the reconnection, and a bi-directional jet forms. This is consistent with what is expected for UV bursts or explosive events, and we provide a self-consistent model of the formation of the reconnection region in such events. The gravitational stratification gives a natural explanation for why explosive events are restricted to a temperature range around a few 0.1 MK, and the presence of plasmoids in the reconnection process provides an understanding of the observed variability during the transient events on a timescale of minutes. Conclusions. Our numerical experiments provide a comprehensive understanding of UV bursts and explosive events, in particular of how the atmospheric response changes if the reconnection happens at different plasma-β, that is, at different heights in the atmosphere. This analysis also gives new insight into how UV bursts might be related to the photospheric Ellerman bombs.
The skeleton is the most common metastatic site for breast cancer, with bone metastasis causing pain as well as risk of pathological fractures. Interaction between tumors and the bone ...microenvironment creates a vicious cycle that accelerates both bone destruction and cancer progression. This study is the first to analyze the soluble factors secreted by breast tumor-associated osteoblasts (TAOBs), which are responsible for promoting cancer progression. The addition of CXCL5 (chemokine (C-X-C motif) ligand 5), present in large amounts in TAOB-condition medium (TAOB-CM), mimicked the inductive effect of TAOB-CM on breast cancer epithelial-mesenchymal transition, migration and invasion. In contrast, inhibition of CXCL5 in OBs decreased TAOB-mediated cancer progression. Inducement of MCF-7 and MDA-MB-231 cancer progression by TAOB-derived CXCL5 is associated with increased Raf/MEK/ERK activation, and mitogen- and stress-activated protein kinase 1 (MSK1) and Elk-1 phosphorylation, as well as Snail upregulation. Activation of Elk-1 facilitates recruitment of phosphorylated MSK1, which in turn enhances histone H3 acetylation and phosphorylation (serine 10) of Snail promoter, resulting in Snail enhancement and E-cadherin downregulation. Moreover, mice treated with anti-CXCL5 antibodies showed decreased metastasis of 4T1 breast cancer cells. Our study suggests that inhibition of CXCL5-mediated ERK/Snail signaling is an attractive therapeutic target for treating metastases in breast cancer patients.
The c-Jun NH2-terminal kinase (JNK) pathway represents one subgroup of MAP kinases that are activated primarily by cytokines and exposure to environmental stress. Autophagy is a protein-degradation ...system characterized by the formation of double-membrane vacuoles termed autophagosomes. Autophagy-related gene beclin 1 plays a key role in autophagosome formation. However, the relationships between activation of JNK pathway, autophagy induction and Beclin 1 expression remain elusive. In this study, we used human cancer cell lines CNE2 and Hep3B to investigate the role of JNK-mediated Beclin 1 expression in ceramide-induced autophagic cell death. Ceramide-treated cells exhibited the characteristics of autophagy (that is, acidic vesicular organelle formation and the LC3-II generation). JNK was activated in these two cell lines exposed to ceramide and the phosphorylation of c-Jun also increased. In the meantime, we found that ceramide upregulated Beclin 1 expression in cancer cells. The upregulation of Beclin 1 expression could be blocked by SP600125 (a specific inhibitor of JNK) or a small interfering RNA (siRNA) directed against JNK1/2 or c-Jun. Chromatin immunoprecipitation and luciferase reporter analysis revealed that c-Jun was involved in the regulation of beclin 1 transcription in response to ceramide treatment. In addition, inhibition of JNK activity by SP600125 could inhibit autophagy induction by ceramide. Furthermore, Beclin 1 knockdown by siRNA also inhibited ceramide-mediated autophagic cell death. JNK-mediated Beclin 1 expression was also observed in topotecan-induced autophagy. These data suggest that activation of JNK pathway can mediate Beclin 1 expression, which plays a key role in autophagic cell death in cancer cells.
Events mediating transformation from the pre-malignant monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) are unknown. We analyzed gene expression data sets generated ...on the Affymetrix U133 platform from 22 MGUS and 101 MM patients using gene-set enrichment analysis. Genes overexpressed in MM were enriched for cell cycle, proliferation and MYC activation gene sets. Upon dissecting the relationship between MYC and cell-cycle gene sets, we identified and validated an MYC activation signature dissociated from proliferation. Applying this signature, MYC is activated in 67% of myeloma, but not in MGUS. This was further confirmed by immunohistochemistry (IHC) using membrane CD138 and nuclear MYC double staining. We also showed that almost all tumors with RAS mutations expressed the MYC activation signature, and multiple mechanisms may be involved in activating MYC. MYC activation, whether assessed by gene-expression signature or IHC, is associated with hyperdiploid MM and shorter survival even in tumors that are not proliferative. Bortezomib treatment is able to overcome the survival disadvantage in patients with MYC activation.
Carbonaceous particulate matter (PM), comprising black carbon (BC), primary organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging of precursors), is a highly toxic vehicle ...exhaust component. Therefore, understanding vehicle pollution requires knowledge of both primary emissions, and how these emissions age in the atmosphere. We provide a systematic examination of carbonaceous PM emissions and parameterisation of SOA formation from modern diesel and gasoline cars at different temperatures (22, -7 °C) during controlled laboratory experiments. Carbonaceous PM emission and SOA formation is markedly higher from gasoline than diesel particle filter (DPF) and catalyst-equipped diesel cars, more so at -7 °C, contrasting with nitrogen oxides (NO
). Higher SOA formation from gasoline cars and primary emission reductions for diesels implies gasoline cars will increasingly dominate vehicular total carbonaceous PM, though older non-DPF-equipped diesels will continue to dominate the primary fraction for some time. Supported by state-of-the-art source apportionment of ambient fossil fuel derived PM, our results show that whether gasoline or diesel cars are more polluting depends on the pollutant in question, i.e. that diesel cars are not necessarily worse polluters than gasoline cars.
. Chang S‐N, Tsai C‐T, Wu C‐K, Lee J‐K, Lai L‐P, Huang S‐W, Huang L‐Y, Tseng C‐D, Lin J‐L, Chiang F‐T, Hwang J‐J (National Taiwan University Hospital Yun‐Lin Branch, Yun‐Lin; National Taiwan ...University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C‐reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305–315.
Objectives. In a large population‐based cohort, the level of C‐reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown.
Methods. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association.
Results. Three polymorphisms (T‐861C, A‐821G and C‐390A/C‐390T) were found in the 1‐kb promoter of CRP. A triallelic polymorphism (C‐390A/C‐390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The −390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L‐type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts.
Conclusion. A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.
Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic ...Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.
Renewed growth of atmospheric methane Rigby, M.; Prinn, R. G.; Fraser, P. J. ...
Geophysical research letters,
November 2008, Letnik:
35, Številka:
22
Journal Article
Recenzirano
Odprti dostop
Following almost a decade with little change in global atmospheric methane mole fraction, we present measurements from the Advanced Global Atmospheric Gases Experiment (AGAGE) and the Australian ...Commonwealth Scientific and Industrial Research Organisation (CSIRO) networks that show renewed growth starting near the beginning of 2007. Remarkably, a similar growth rate is found at all monitoring locations from this time until the latest measurements. We use these data, along with an inverse method applied to a simple model of atmospheric chemistry and transport, to investigate the possible drivers of the rise. Specifically, the relative roles of an increase in emission rate or a decrease in concentration of the hydroxyl radical, the largest methane sink, are examined. We conclude that: 1) if the annual mean hydroxyl radical concentration did not change, a substantial increase in emissions was required simultaneously in both hemispheres between 2006 and 2007; 2) if a small drop in the hydroxyl radical concentration occurred, consistent with AGAGE methyl chloroform measurements, the emission increase is more strongly biased to the Northern Hemisphere.
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