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.
CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
In August 2016, continuous measurements of volatile organic compounds (VOCs) and trace gases were conducted at an urban site in Wuhan. Four high-ozone (O3) days and twenty-seven non-high-O3 days were ...identified according to the China's National Standard Level II (∼100 ppbv). The occurrence of high-O3 days was accompanied by tropical cyclones. Much higher concentrations of VOCs and carbon monoxide (CO) were observed on the high-O3 days (p < 0.01). Model simulations revealed that vehicle exhausts were the dominant sources of VOCs, contributing 45.4 ± 5.2% and 37.3 ± 2.9% during high-O3 and non-high-O3 days, respectively. Both vehicle exhausts and stationary combustion made significantly larger contributions to O3 production on high-O3 days (p < 0.01). Analysis using a chemical transport model found that local photochemical formation accounted for 74.7 ± 5.8% of the daytime O3, around twice the regional transport (32.2 ± 5.4%), while the nighttime O3 was mainly attributable to regional transport (59.1 ± 9.9%). The local O3 formation was generally limited by VOCs in urban Wuhan. To effectively control O3 pollution, the reduction ratio of VOCs to NOx concentrations should not be lower than 0.73, and the most efficient O3 abatement could be achieved by reducing VOCs from vehicle exhausts. This study contributes to the worldwide database of O3-VOC-NOx sensitivity research. Its findings will be helpful in formulating and implementing emission control strategies for dealing with O3 pollution in Wuhan.
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•Vehicular emissions were the largest contributor to VOCs in Wuhan.•VOCs from vehicular exhausts made the highest contribution to O3 formation.•Regional transport accounted for ∼60% and ∼30% of nighttime and daytime O3, respectively.•The reduction ratio of VOCs to NOx concentrations should not be lower than 0.73 for effective O3 control.
Local formation dominated daytime O3, while nighttime O3 was attributable to regional transport in Wuhan.
Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
For metallic single crystals with dimensions in the micrometer and sub-micrometer regime, systematic studies have established that sample size has an obvious influence on the apparent strength, ...following a “smaller is stronger” trend. For amorphous metals, several metallic glasses (MG) appear to exhibit a similar trend, while a few others do not. Here, another MG is examined, Al88Fe7Gd5, using quantitative in situ tensile and compression tests inside electron microscopes, with sample effective diameter covering a wide range (100nm to 3μm). A clearly elevated strength is observed, as high as about twice the value of bulk samples, for samples with diameters approaching 100nm. A size regime is proposed, where the strength is controlled by the nucleation of the shear band, starting from its embryonic stage: the smaller the sample size, the more difficult this nucleation becomes. The size dependence is also discussed from an energy balance perspective: the resulting simple power law fits the data as well as other published strength data for a number of MG systems.
Abstract Introduction The inflammatory response plays an important role in liver dysfunction after hepatic ischemia/reperfusion (I/R), which is tightly regulated by the Toll-like receptor 2 ...(TLR2)/nuclear factor (NF)-κB pathway; suppression of TLR2/NF-κB signaling has therefore become a promising target for anti-inflammatory treatment in hepatic I/R injury. Erythropoietin (EPO) is a glycoprotein cytokine produced primarily by the kidney that has anti-inflammatory activities. The purpose of the present study was to investigate the effect of EPO preconditioning, if any, against hepatic I/R injury in rats and its underlying mechanisms. Materials and Methods Male Sprague-Dawley rats were subjected to partial (70%) hepatic ischemia for 45 minutes after pretreatment with either saline or EPO followed by 24-hour reperfusion. Hepatic injury was evaluated according to biochemical and histopathologic examinations. The expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured by using enzyme-linked immunosorbent assay and real-time polymerase chain reaction. The expression of nuclear translocation and phosphorylation of NF-κB p65, EPOR receptor (EPOR), p-EPOR, p-IκB-α, IκB-α, and TLR2 were determined by using Western blot analysis. Results EPO treatment significantly improved hepatic function and histology, as indicated by reduced transaminase levels and pathologic changes. The expression of TNF-α, IL-1β, IL-6, p-IκB-α, and TLR2 was significantly decreased with up-regulation of p-EPOR by EPO. Moreover, EPO pretreatment also reduced I/R-induced the phosphorylation and nuclear translocation of NF-κB p65 subunits in liver tissue, but EPO had no influence on the expression of p65 and IκB-α. Conclusions These results suggest that EPO pretreatment ameliorates hepatic I/R injury, which is involved in suppressing TLR2/NF-κB–mediated inflammation.
Interfaces such as twin boundaries, stacking faults and grain boundaries often play an important role in controlling mechanical properties of metals through interaction with dislocations. Segregation ...of alloy elements and impurities to these interfaces can stabilize them and produce a large strengthening effect. Here we report the effect of Ag on segregation of alloy elements at twin boundaries, stacking faults and grain boundaries in the Mg–Gd system. Specifically, for the first time a spinal-shaped periodic segregation is observed at the {101¯2} twin boundary and high-angle lamellar grain boundary in the Mg–Gd–Y–Zr alloy due to the presence of the Ag addition. The segregation consists of Gd- and Ag-rich columns. It appears that high Ag content in the spinal-shaped segregation induces fcc-like cell structures.
Essentials
Positive family histories suggest the existence of hereditary immune thrombocytopenia (ITP).
The predisposing gene for familial ITP was screened in two familial ITP patients.
The G76S ...mutation on TNFRSF13B led to immune dysfunction and induced megakaryocyte apoptosis.
The G76S mutation on TNFRSF13B is a gain‐of‐function mutation and a predisposing variant for ITP.
Summary
Background
Most immune thrombocytopenia (ITP) is sporadic but a positive family history of ITP in some patients suggests that hereditary forms exist. Because of the rarity of familial ITP families available for study and the heterogeneity of sporadic ITP, family linkage analysis or genome‐wide association studies are limited.
Objectives
Based on one ITP pedigree, we try to identify the predisposing gene in familial or sporadic ITP and reveal the way in which it causes thrombocytopenia.
Methods
Gene expression profiling analysis and whole‐exome sequencing were performed on samples from family members with ITP, sporadic ITP cases and healthy individuals. We also evaluated the influence of potential pathogenic mutation on immune function and megakaryocyte apoptosis.
Results
Whole‐exome sequencing identified a potential pathologic p.G76S heterozygous mutation on the TNFRSF13B gene in familial ITP patients. ITP patients harboring the G76S mutation displayed an upregulated ‘cytokine–cytokine receptor interaction’ signal, increased serum TNFα, IL‐17α, IFNγ and BAFF levels, and enhanced binding capacity of APRIL ligand to B cells. Additionally, Epstein‐Barr virus (EBV)‐transformed B cells with the G76S mutation could induce human megakaryocyte line (Meg‐01) apoptosis significantly.
Conclusion
p.G76S mutation on the TNFRSF13B gene is responsible for ITP, and is a genetic predisposing factor for familial or sporadic ITP.
We report a significant grain size effect on radiation tolerance of nanocrystalline Mo under He ion irradiation. Irradiation-induced dislocation loops mainly contribute to the irradiation-induced ...hardening of Mo films with grain size of >90nm, while few such loops in those with grain size of <90nm. The hardness increment after irradiation decreases with decreasing the grain size, and approaches zero at the grain size of 25nm. Also, the size and the density of irradiation-induced He bubbles decrease as the grain size decreases. This observation provides direct evidence that nanocrystalline body-centered-cubic metals have greater radiation tolerance than their ultra-fine-grained or coarse-grained counterparts.
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In this Letter, we study the kinematic properties of ascending hot blobs associated with confined flares. Taking advantage of high-cadence extreme-ultraviolet images provided by the Atmospheric ...Imaging Assembly on board the Solar Dynamics Observatory, we find that for the 26 events selected here, the hot blobs are first impulsively accelerated outward, but then quickly slow down to motionlessness. Their velocity evolution is basically synchronous with the temporal variation of the Geostationary Operational Environmental Satellite soft X-ray flux of the associated flares, except that the velocity peak precedes the soft X-ray peak by minutes. Moreover, the duration of the acceleration phase of the erupting blobs is moderately correlated with that of the flare rise phase. For nine of the 26 cases, the erupting blobs even appear minutes prior to the onset of the associated flares. Our results show that a fraction of confined flares also involve the eruption of a magnetic flux rope, which sometimes is formed and heated prior to the flare onset. We suggest that the initiation and development of these confined flares are similar to that of eruptive ones, and the main difference may lie in the background field constraint, which is stronger for the former than for the latter.
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