An accurate speciation mapping of non-methane volatile organic compounds (NMVOC) emissions has an important impact on the performance of chemical transport models (CTMs) in simulating ozone mixing ...ratios and secondary organic aerosols. Taking the INTEX-B Asian NMVOC emission inventory as the case, we developed an improved speciation framework to generate model-ready anthropogenic NMVOC emissions for various gas-phase chemical mechanisms commonly used in CTMs in this work, by using an explicit assignment approach and updated NMVOC profiles. NMVOC profiles were selected and aggregated from a wide range of new measurements and the SPECIATE database v.4.2. To reduce potential uncertainty from individual measurements, composite profiles were developed by grouping and averaging source profiles from the same category. The fractions of oxygenated volatile organic compounds (OVOC) were corrected during the compositing process for those profiles which used improper sampling and analyzing methods. Emissions of individual species were then lumped into species in different chemical mechanisms used in CTMs by applying mechanism-dependent species mapping tables, which overcomes the weakness of inaccurate mapping in previous studies. Emission estimates for individual NMVOC species differ between one and three orders of magnitude for some species when different sets of profiles are used, indicating that source profile is the most important source of uncertainties of individual species emissions. However, those differences are diminished in lumped species as a result of the lumping in the chemical mechanisms. Gridded emissions for eight chemical mechanisms at 30 min × 30 min resolution as well as the auxiliary data are available at http://mic.greenresource.cn/intex-b2006. The framework proposed in this work can be also used to develop speciated NMVOC emissions for other regions.
A large change in albedo has a significant effect on glacier ablation. Atmospheric aerosols – e.g. black carbon (BC) and dust – can reduce the albedo of glaciers and thus contribute to their melting. ...In this study, two main themes were explored: (1) the decrease in albedo of the Zhadang glacier on Mt. Nyainqentanglha between 2001 and 2012, as observed by the Moderate Resolution Imaging Spectroradiometer (MODIS) on-board the Terra satellite, and the correlation of this albedo with mass balance; and (2) the concentrations of BC and dust in the glacier measured during 2012, and the associated impacts of these impurities on albedo and radiative forcings (RF). The average albedo of the Zhadang glacier from the MODIS increased with the altitude and fluctuated but had a decreasing trend (−0.003 a−1) during the period 2001–2012, with the highest (0.722) in 2003 and the lowest (0.597) in 2009 and 2010. The mass balance of the glacier has a positively significant correlation with its surface albedo derived from MODIS. Snow samples were collected on the Zhadang glacier to measure the BC and dust in the summer of 2012. The impacts of BC and dust on albedo reduction in different melting conditions were identified with the SNow ICe Aerosol Radiative (SNICAR) model initiated by in situ observation data. The sensitivity analysis showed that BC was a major factor in albedo reduction when the glacier was covered by newly fallen snow. Nevertheless, the contribution of dust to albedo reduction can reach as high as 56%, much exceeding that of BC (28%), when the glacier experiences strong surficial melting and its surface is almost bare ice. The average RF caused by dust could increase from 1.1 to 8.6 W m−2, exceeding the RF caused by BC after snow was deposited and surface melting occurred in the Zhadang glacier. This implies that it may be dust that primarily dominates the melting of some glaciers in the inner Tibetan Plateau during melting seasons, rather than BC.
Prediction of the
(IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our ...aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
Ninety-three patients with World Health Organization grade II gliomas with known
mutation and 1p/19q-codeletion status (18
wild-type, 45
mutant and no 1p/19q codeletion, 30
mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the
-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for
wild-type tumors and 1p/19q-codeletion status in
-mutant subgroups were evaluated using the least absolute shrinkage and selection operator.
Various histogram and texture parameters differed significantly according to
-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an
wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in
-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807.
Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
Abstract Radiation-induced toxicity limits the delivery of high-dose radiation to head and neck lesions. The aim of this study was to investigate the effectiveness of epicatechin (EC), a minor ...component of green tea extract, on radiation-induced ototoxicity in vitro and in vivo . The effect of EC on radiation-induced cytotoxicity was analyzed in the organ of Corti-derived cell lines, HEI-OC1 and UB-OC1. The cell viability, apoptosis, reactive oxygen species generation, and mitochondrial membrane potential as well as changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of hearing protection and drug toxicity of EC were explored in a zebrafish and rat model. Radiation-induced apoptosis and altered mitochondrial membrane potential in HEI-OC1 and UB-OC1 were observed. EC inhibited radiation-induced apoptosis and intracellular reactive oxygen species generation. EC markedly attenuated the radiation-induced embryotoxicity and protected against radiation-induced loss and changes of auditory neuromast in the zebrafish. In addition, intratympanic administration of EC was protective against radiation-induced hearing loss in the rat model, as determined by click-evoked auditory brainstem ( P <0.01). EC significantly reduced the expression of p-JNK, p-ERK cleaved caspase-3, and cleaved PARP compared to their significant increase after radiation treatment. The results of this study suggest that EC significantly inhibited radiation-induced apoptosis in auditory hair cells and may be a safe and effective candidate treatment for the prevention of radiation-induced ototoxicity.
Shuttling protons in ammonia synthesis
An electrochemical route to ammonia could substantially lower the greenhouse gas emissions associated with the current thermal Haber-Bosch process. One ...relatively promising option under study involves reductive formation of lithium nitride, which can be protonated to ammonia. However, the ethanol used to date as a local proton source in these studies may degrade under the reaction conditions. Suryanto
et al.
report the use of a tetraalkyl phosphonium salt in place of ethanol (see the Perspective by Westhead
et al.
). This cation can stably undergo deprotonation–reprotonation cycles and, as an added benefit, it enhances the ionic conductivity of the medium.
Science
, abg2371, this issue p.
1187
; see also abi8329, p.
1149
A phosphonium cation acts as a stable proton shuttle during electrochemical ammonia synthesis.
Ammonia (NH
3
) is a globally important commodity for fertilizer production, but its synthesis by the Haber-Bosch process causes substantial emissions of carbon dioxide. Alternative, zero-carbon emission NH
3
synthesis methods being explored include the promising electrochemical lithium-mediated nitrogen reduction reaction, which has nonetheless required sacrificial sources of protons. In this study, a phosphonium salt is introduced as a proton shuttle to help resolve this limitation. The salt also provides additional ionic conductivity, enabling high NH
3
production rates of 53 ± 1 nanomoles per second per square centimeter at 69 ± 1% faradaic efficiency in 20-hour experiments under 0.5-bar hydrogen and 19.5-bar nitrogen. Continuous operation for more than 3 days is demonstrated.
SOX2 is a well-known core transcription factor in embryonic stem cells (ESCs) and has an important role in the maintenance of pluripotency. Recently, SOX2 expression has also been reported in adult ...stem cells (ASCs), but the role of SOX2 in ASCs remains unknown. In this study, we examined the molecular mechanisms of SOX2 in human mesenchymal stem cells (hMSCs), a type of ASCs, by performing inhibition studies. SOX2 inhibition resulted in altered cell growth and differentiation capabilities. These changes coincided with a decrease in Dickkopf-1 (DKK1), a soluble inhibitor of WNT signaling. Chromatin immunoprecipitation and luciferase assays showed that SOX2 binds to DKK1 and has a positive regulatory role in transcription. The enforced expression of DKK1 in SOX2-inhibited hMSCs reversed the differentiation deformities, but could not abrogate the cell proliferation defect. Proliferation was regulated by c-MYC, whose expression can also be controlled by SOX2. Our study shows that SOX2 directly regulates DKK1 expression and, as a consequence, determines the differentiation lineage of hMSCs. Moreover, SOX2 also regulates proliferation by affecting c-MYC. Therefore, these results suggest that SOX2 might have a specific function by regulating DKK1 and c-MYC in the differentiation and growth of ASCs, which is separate from its roles in ESCs.
A Case Study on the Origin of Near‐Earth Plasma Glocer, A.; Welling, D.; Chappell, C. R. ...
Journal of geophysical research. Space physics,
November 2020, Letnik:
125, Številka:
11
Journal Article
Recenzirano
Odprti dostop
This study presents simulations of the coupled space environment during a geomagnetic storm that separates the different sources of near‐Earth plasma. These simulations include separate fluids for ...solar wind and ionospheric protons, ionospheric oxygen, and the plasmasphere. Additionally, they include the effects of both a hot ring current population and a cold plasmaspheric population simultaneously for a geomagnetic storm. The modeled ring current population represents the solution of bounce‐averaged kinetic solution; the core plasmaspheric model assumes a fixed temperature of 1 eV and constant pressure along the field line. We find that during the storm, ionospheric protons can be a major contributor to the plasmasheet and ring current and that ionospheric plasma can largely displace solar wind protons in much of the magnetosphere under certain conditions. Indeed, the ionospheric source of plasma cannot be ignored. Significant hemispheric asymmetry is found between the outflow calculated in the summer and winter hemispheres, consistent with past observations. That asymmetric outflow is found to lead to asymmetric filling of the lobes, with the northern (summer) lobe receiving more outflow that has a higher proportion of O+ and the southern (winter) lobe receiving less outflow with a higher proportion of H+. We moreover find that the inclusion of the plasmasphere can have a system‐wide impact. Specifically, when the plasmasphere drainage plume reaches the magnetopause, it can reduce the reconnection rate, suppress ionospheric outflow and change its composition, change the composition in the magnetosphere, and reduce the ring current intensity.
Key Points
Ionospheric H+ is a critically important contributor to the magnetosphere during a storm
Seasonal effect on outflow create asymmetric filling of the lobes
The inclusion of an additional plasmaspheric fluid has system‐wide effects
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of ...programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated. Here, we analyzed gene expression profiles (GEPs) using RNA from baseline tumor samples of pembrolizumab-treated patients. We identified immune-related signatures correlating with clinical benefit using a learn-and-confirm paradigm based on data from different clinical studies of pembrolizumab, starting with a small pilot of 19 melanoma patients and eventually defining a pan-tumor T cell-inflamed GEP in 220 patients with 9 cancers. Predictive value was independently confirmed and compared with that of PD-L1 immunohistochemistry in 96 patients with head and neck squamous cell carcinoma. The T cell-inflamed GEP contained IFN-γ-responsive genes related to antigen presentation, chemokine expression, cytotoxic activity, and adaptive immune resistance, and these features were necessary, but not always sufficient, for clinical benefit. The T cell-inflamed GEP has been developed into a clinical-grade assay that is currently being evaluated in ongoing pembrolizumab trials.
The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch ...repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair–deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.
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