A supercritical carbon dioxide layer in the Hadean atmosphere for the origin of life?

Zhang et al.[1] reported the first direct detection of the natural supercritical CO2 (scCO2;critical point:31.1 ℃ and 72.9 atm) in a deep-sea hydrothermal syste...     

空域色噪声背景下双基地MIMO雷达角度估计

空域有色噪声会导致现有多输入多输出(multiple input multiple output,MIMO)雷达算法性能下降,甚至完全失效.针对空域色噪声背景下双基地MIMO雷达联合波离角(direction of departure,DOD)和波达角(direction of arrival,DOA)估计问题,分析了...     

Efficient and stable inverted perovskite solar cells enabled by inhibition of self-aggregation of fullerene electron-transporting compounds

Fullerene-based electron-transporting layers (ETLs) significantly influence the defect passivation and device performance of inverted perovskite solar cells (PS...     

Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina

Retinitis pigmentosa (RP) is a form of inherited retinal degenerative diseases that ultimately involves the macula,which is present in primates but not in the r...     

Human exposome and biomarker database for soil pollutants at typical sites of industrial contamination

Rapid economic development and industrialization have left many risk sites around the world with significant or potential soil contamination due to industrial p...     

Platelet-derived growth factor receptor beta identifies mesenchymal stem cells with enhanced engraftment to tissue injury and pro-angiogenic property

Mesenchymal stem cells (MSCs) are heterogeneous likely consisting of subpopulations with various therapeutic potentials. Here we attempted to acquire a subset of MSCs with enhanced effect in wound healing. We found that human placental MSCs expressing platelet-derived growth factor (PDGF) receptor (PDGFR)-β exhibited greater proliferation rates and generated more colony-forming unit-fibroblast (CFU-F), compared to PDGFR-β^? MSCs. Notably, PDGFR-β⁺ MSCs expressed higher levels of pro-angiogenic factors such as Ang1, Ang2, VEGF, bFGF and PDGF. When 10⁶ GFP-expressing MSCs were topically applied into excisional wounds in mice, PDGFR-β⁺ MSCs actively incorporated into the wound tissue, resulting in enhanced engraftment (3.92 ± 0.31 × 10⁵ remained in wound by 7 days) and accelerated wound closure; meanwhile, PDGFR-β^? MSCs tended to remain on the top of the wound bed with significantly fewer cells (2.46 ± 0.26 × 10⁵) engrafted into the wound, suggesting enhanced chemotactic migration and engraftment of PDGFR-β⁺ MSCs into the wound. Real-Time PCR and immunostain analyses revealed that the expression of PDGF-B was upregulated after wounding; transwell migration assay showed that PDGFR-β⁺ MSCs migrated eightfold more than PDGFR-β^? MSCs toward PDGF-BB. Intriguingly, PDGFR-β⁺ MSC-treated wounds showed significantly enhanced angiogenesis compared to PDGFR-β^? MSC- or vehicle-treated wounds. Thus, our results indicate that PDGFR-β identifies a subset of MSCs with enhanced chemotactic migration to wound injury and effect in promoting angiogenesis and wound healing, implying a greater therapeutic potential for certain diseases.     

Model averaging estimation for conditional volatility models with an application to stock market volatility forecast

This paper is concerned with model averaging estimation for conditional volatility models. Given a set of candidate models with different functional forms, we propose a model averaging estimator and forecast for conditional volatility, and construct the corresponding weight-choosing criterion. Under some regulatory conditions, we show that the weight selected by the criterion asymptotically minimizes the true Kullback–Leibler divergence, which is the distributional approximation error, as well as the Itakura–Saito distance, which is the distance between the true and estimated or forecast conditional volatility. Monte Carlo experiments support our newly proposed method. As for the empirical applications of our method, we investigate a total of nine major stock market indices and make a 1-day-ahead volatility forecast for each data set. Empirical results show that the model averaging forecast achieves the highest accuracy in terms of all types of loss functions in most cases, which captures the movement of the unknown true conditional volatility.     

Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD

The type III receptor tyrosine kinase FLT3 is frequently mutated in acute myeloid leukemia. Oncogenic FLT3 mutants display constitutive activity leading to aberrant cell proliferation and survival. Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. The position of this tyrosine residue is well conserved in all receptor tyrosine kinases. It has been reported that phosphorylation of the activation loop tyrosine is critical for catalytic activity for some but not all receptor tyrosine kinases. The role of Y842 residue in FLT3 signaling has not yet been studied. In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. Microarray analysis comparing gene expression regulated by FLT3-ITD versus FLT3-ITD/Y842F demonstrated that mutation of Y842 causes suppression of anti-apoptotic genes. Furthermore, we showed that cells expressing FLT3-ITD/Y842F display impaired activity of the RAS/ERK pathway due to reduced interaction between FLT3 and SHP2 leading to reduced SHP2 activation. Thus, we suggest that Y842 is critical for FLT3-mediated RAS/ERK signaling and cellular transformation.