Because the surface-to-volume ratio of quasi-two-dimensional materials is extremely high, understanding their surface characteristics is crucial for practically controlling their intrinsic properties ...and fabricating p-type and n-type layered semiconductors. Van der Waals crystals are expected to have an inert surface because of the absence of dangling bonds. However, here we show that the surface of high-quality synthesized molybdenum disulfide (MoS2) is a major n-doping source. The surface electron concentration of MoS2 is nearly four orders of magnitude higher than that of its inner bulk. Substantial thickness-dependent conductivity in MoS2 nanoflakes was observed. The transfer length method suggested the current transport in MoS2 following a two-dimensional behavior rather than the conventional three-dimensional mode. Scanning tunneling microscopy and angle-resolved photoemission spectroscopy measurements confirmed the presence of surface electron accumulation in this layered material. Notably, the in situ-cleaved surface exhibited a nearly intrinsic state without electron accumulation.
Runt-related transcription factor 1 (RUNX1) is essential for normal hematopoiesis. RUNX1 mutations have rarely been reported in chronic myelomonocytic leukemia (CMML). We examined RUNX1 mutations in ...81 patients with CMML at initial diagnosis. Mutational analysis was performed on bone marrow samples by direct sequencing of all reverse transcription PCR products amplified with three primer pairs that cover the entire coding sequences of RUNX1b. Thirty-two RUNX1 mutations were detected in 30 patients (37%); 23 mutants were located in the N-terminal part and 9 in the C-terminal region. The mutations consisted of 9 missense, 1 silent, 7 nonsense and 15 frameshift mutations. Two patients had biallelic heterozygous mutations. There was no difference in overall survival between patients with and without RUNX1 mutations, but a trend of higher risk of acute myeloid leukemia (AML) progression was observed in mutation-positive patients (16/30 vs 17/51, P=0.102), especially in patients with C-terminal mutations (P=0.023). The median time to AML progression was 6.8 months in patients with C-terminal mutations compared with 28.3 months in those without mutations (P=0.022). This study showed for the first time a high frequency of RUNX1 mutations in CMML. C-terminal mutations might be associated with a more frequent and rapid AML transformation.
In a trial involving 304 veterans with stable PTSD, prazosin did not alleviate distressing dreams and did not improve sleep quality or overall clinical symptoms over 10 or 26 weeks. This result is in ...contrast to findings in several previous smaller or briefer trials.
Designer nanoparticles with controlled shapes and sizes are increasingly popular vehicles for therapeutic delivery due to their enhanced cell-delivery performance. However, our ability to fashion ...nanoparticles has offered only limited control over these parameters. Structural DNA nanotechnology has an unparalleled ability to self-assemble three-dimensional nanostructures with near-atomic resolution features, and thus, it offers an attractive platform for the systematic exploration of the parameter space relevant to nanoparticle uptake by living cells. In this study, we examined the cell uptake of a panel of 11 distinct DNA-origami shapes, with the largest dimension ranging from 50–400 nm, in 3 different cell lines. We found that larger particles with a greater compactness were preferentially internalized compared with elongated, high-aspect-ratio particles. Uptake kinetics were also found to be more cell-type-dependent than shape-dependent, with specialized endocytosing dendritic cells failing to saturate over 12 h of study. The knowledge gained in the current study furthers our understanding of how particle shape affects cellular uptake and heralds the development of DNA nanotechnologies toward the improvement of current state-of-the-art cell-delivery vehicles.
DNA nanostructures have evoked great interest as potential therapeutics and diagnostics due to ease and robustness of programming their shapes, site-specific functionalizations and responsive ...behaviours. However, their utility in biological fluids can be compromised through denaturation induced by physiological salt concentrations and degradation mediated by nucleases. Here we demonstrate that DNA nanostructures coated by oligolysines to 0.5:1 N:P (ratio of nitrogen in lysine to phosphorus in DNA), are stable in low salt and up to tenfold more resistant to DNase I digestion than when uncoated. Higher N:P ratios can lead to aggregation, but this can be circumvented by coating instead with an oligolysine-PEG copolymer, enabling up to a 1,000-fold protection against digestion by serum nucleases. Oligolysine-PEG-stabilized DNA nanostructures survive uptake into endosomal compartments and, in a mouse model, exhibit a modest increase in pharmacokinetic bioavailability. Thus, oligolysine-PEG is a one-step, structure-independent approach that provides low-cost and effective protection of DNA nanostructures for in vivo applications.
We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes ...to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser(473) and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.
PC12 cells were used to examine the in vitro antioxidative and anti-inflammatory effects of oleanolic acid (OA) and ursolic acid (UA). PC12 cells were pretreated with OA or UA at 20 and 40 μM and ...followed by exposure of hydrogen peroxide (H₂O₂) or 1-methyl-4-phenylpyridinium ion (MPP⁺) to induce cell injury. Results showed that H₂O₂- or MPP⁺-treatment significantly decreased cell viability and increased lactate dehydrogenase (LDH) release (P < 0.05). The pretreatment from OA or UA significantly and concentration-dependently reduced subsequent H₂O₂- or MPP⁺-induced cell death and LDH release (P < 0.05). Either H₂O₂- or MPP⁺-treatment significantly increased malonyldialdehyde (MDA) formation, decreased glutathione (GSH) content, and diminished glutathione peroxidase (GPX), catalase, and superoxide dismutase (SOD) activities (P < 0.05). The pretreatment from OA or UA significantly retained GSH, and reversed H₂O₂- and MPP⁺-induced impairment in catalase and SOD activities (P < 0.05), and decreased MDA formation (P < 0.05). Either H₂O₂- or MPP⁺-treatment significantly elevated interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α levels (P < 0.05). The pretreatments from OA or UA significantly attenuated subsequent H₂O₂- or MPP⁺-induced release of IL-6 and TNF-α (P < 0.05). Based on the observed antioxidative and anti-inflammatory activities from OA and UA, these 2 compounds were potent agents against neurodegenerative disorder.
Surface passivation is a promising technique for improving the corrosion resistance both in vitro and in vivo as well as the biocompatibility of 316L stainless steel. In this work, we studied the ...effect of different passivative processes on the in vitro corrosion resistance of 316L stainless steel wire. Characterization techniques such as anodic polarization test, scanning electron microscopy, auger electron spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy were employed to co-relate the corrosion behavior to various surface characteristics and surface treatments. Results showed that all of these surface treatments did not improve the corrosion resistance of the alloy satisfactorily except amorphous oxidation. This improvement is attributed to the removal of plastically deformed native air-formed oxide layer and the replacement of a newly grown, more uniform and compact one which is composed of nano-scale oxide particles with higher oxygen and chromium concentrations. The properties of surface oxide layer, rather than its thickness, seem to be the predominant factor to explain the improvement of in vitro corrosion resistance.
THE ARCTIC SYSTEM REANALYSIS, VERSION 2 Bromwich, D. H.; Wilson, A. B.; Bai, L. ...
Bulletin of the American Meteorological Society,
04/2018, Letnik:
99, Številka:
4
Journal Article
Recenzirano
The Arctic is a vital component of the global climate, and its rapid environmental evolution is an important element of climate change around the world. To detect and diagnose the changes occurring ...to the coupled Arctic climate system, a state-of-the-art synthesis for assessment and monitoring is imperative. This paper presents the Arctic System Reanalysis, version 2 (ASRv2), a multiagency, university-led retrospective analysis (reanalysis) of the greater Arctic region using blends of the polar-optimized version of the Weather Research and Forecasting (Polar WRF) Model and WRF three-dimensional variational data assimilated observations for a comprehensive integration of the regional climate of the Arctic for 2000–12. New features in ASRv2 compared to version 1 (ASRv1) include 1) higher-resolution depiction in space (15-km horizontal resolution), 2) updated model physics including subgrid-scale cloud fraction interaction with radiation, and 3) a dual outer-loop routine for more accurate data assimilation. ASRv2 surface and pressure-level products are available at 3-hourly and monthly mean time scales at the National Center for Atmospheric Research (NCAR). Analysis of ASRv2 reveals superior reproduction of near-surface and tropospheric variables. Broadscale analysis of forecast precipitation and site-specific comparisons of downward radiative fluxes demonstrate significant improvement over ASRv1. The high-resolution topography and land surface, including weekly updated vegetation and realistic sea ice fraction, sea ice thickness, and snow-cover depth on sea ice, resolve finescale processes such as topographically forced winds. Thus, ASRv2 permits a reconstruction of the rapid change in the Arctic since the beginning of the twenty-first century–complementing global reanalyses. ASRv2 products will be useful for environmental models, verification of regional processes, or siting of future observation networks.
Aims
To study the association between number and positions of mutations with MICs of fluoroquinolone non‐susceptible Haemophilus influenzae.
Methods and Results
More than 40% of 48 H. influenzae ...isolated from nursing home residents were not susceptible to fluoroquinolone. Amino acid changes in the quinolone resistance determining regions, and correlation with MICs and inhibition zone diameters were analysed. All isolates with reduced susceptibility to fluoroquinolones (MIC ≥0·125 µg ml−1) had at least one mutation in gyrA at position 84 and were resistant to nalidixic acid. Compared to isolates with reduced susceptibility, resistant isolates were associated with mutations in gyrA at positions 88 and 134, and in parC at position 88 (P < 0·001). Inhibition zone diameter for nalidixic acid disk ≥23 mm may detect susceptible isolates.
Conclusions
Reduced susceptibility to fluoroquinolones was associated with mutations at position 84 in gyrA. A further increase in fluoroquinolone MIC was associated with mutations in gyrA at positions 88 and 134, and parC at position 88.
Significance and Impact of the Study
Due to limited resistant H. influenzae strains, prior studies on association between positions of mutations and fluoroquinolone MICs were inconclusive. The comparison of mutations between isolates with susceptibility, reduced susceptibility and high resistance supported the importance of the present study.
PDF
