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The introduction of the Simian virus 40 (SV40) early region, the telomerase catalytic subunit ( hTERT ) and an oncogenic allele of H-Ras directly transforms primary human cells. SV40 small T antigen (ST), which forms a complex with protein phosphatase 2A (PP2A) and inhibits PP2A activity, is believed to have a critical role in the malignant transformation of human cells. Recent evidence has shown that aberrant microRNA (miRNA) expression patterns are correlated with cancer development. Here, we identified miR-27a as a differentially expressed miRNA in SV40 ST-expressing cells. miR-27a is upregulated in SV40 ST-transformed human bronchial epithelial cells (HBERST). Suppression of miR-27a expression in HBERST cells or lung cancer cell lines (NCI-H226 and SK-MES-1) that exhibited high levels of miR-27a expression lead to cell growth arrested in the G 0 –G 1 phase. In addition, suppression of miR-27a in HBERST cells attenuated the capacity of such cells to grow in an anchorage-independent manner. We also found that suppression of the PP2A B56γ expression resulted in upregulation of miR-27a similar to that achieved by the introduction of ST, indicating that dysregulation of miR-27a expression in ST-expressing cells was mediated by the ST–PP2A interaction. Moreover, we discovered that Fbxw7 gene encoding F-box/WD repeat-containing protein 7 was a potential miR-27a target validated by dual-luciferase reporter system analysis. The inverse correlation between miR-27a expression levels and Fbxw7 protein expression was further confirmed in both cell models and human tumor samples. Fbxw7 regulates cell-cycle progression through the ubiquitin-dependent proteolysis of a set of substrates, including c-Myc, c-Jun, cyclin E1 and Notch 1. Thus, promotion of cell growth arising from the suppression of Fbxw7 by miR-27a overexpression might be responsible for the viral oncoprotein ST-induced malignant transformation. These observations demonstrate that miR-27a functions as an oncogene in human tumorigenesis.

The recent discovery of iron ferropnictide superconductors has received intensive concern in connection with magnetically involved superconductors. Prominent features of ferropnictide superconductors are becoming apparent: the parent compounds exhibit an antiferromagnetic ordered spin density wave (SDW) state, the magnetic-phase transition is always accompanied by a crystal structural transition, and superconductivity can be induced by suppressing the SDW phase via either chemical doping or applied external pressure to the parent state. These features generated considerable interest in the interplay between magnetism and structure in chemically doped samples, showing crystal structure transitions always precede or coincide with magnetic transition. Pressure-tuned transition, on the other hand, would be more straightforward to superconducting mechanism studies because there are no disorder effects caused by chemical doping; however, remarkably little is known about the interplay in the parent compounds under controlled pressure due to the experimental challenge of in situ measuring both of magnetic and crystal structure evolution at high pressure and low temperatures. Here we show from combined synchrotron Mössbauer and X-ray diffraction at high pressures that the magnetic ordering surprisingly precedes the structural transition at high pressures in the parent compound BaFe 2 As 2 , in sharp contrast to the chemical-doping case. The results can be well understood in terms of the spin fluctuations in the emerging nematic phase before the long-range magnetic order that sheds light on understanding how the parent compound evolves from a SDW state to a superconducting phase, a key scientific inquiry of iron-based superconductors.

A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo( a )pyrene, aflatoxin B 1 , N -methyl- N ′-nitro- N -nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3′-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4–PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.

In order to enhance the ability of calcium phosphate-based biomaterials for bone defect repair, icariin (Ica), one natural product with ability of promoting osteoblasts differentiation in vitro and enhancing bone formation in vivo, was loaded into porous β-tricalcium phosphate ceramic (β-TCP) disks. The obtained Ica-loaded porous β-TCP ceramic (Ica/β-TCP) disks were characterized by SEM. The SEM photos indicated that the disks had porous structure and the surface morphology of the porous β-TCP ceramic (β-PTCP) disks had no obvious difference from the Ica/β-TCP disks. The Ica release curve of Ica/β-TCP disks showed a burst release during the first 1 day and the concentration of released Ica during the first 3 days had low cytotoxicity. The loading Ica in Ica/β-TCP disks hardly affected the attachment and morphology of Ros17/28 cells, however, the Ica/β-TCP disks were favorable to supporting the proliferation and differentiation of Ros17/28 cells better compared with the β-PTCP disks. There was plenty of bone-like apatite formed on the surface of Ica/β-TCP disks soaked in SBF solution for three days. After back intramuscular implantation of rats for three months, no obvious osteogenic evidence was detected in β-PTCP disks, but new bone formation was observed in Ica/β-TCP disks. Fibrous tissues and slight inflammatory reaction was also found in the Ica/β-TCP disks and β-TCP disks. Therefore, the loading Ica did not change the biocompatibility of β-TCP ceramic, but enhanced the bioactivity of β-TCP ceramic in vivo. The Ica/β-TCP ceramic had potential to be used for bone defect repair.

One of key issues in studying iron based superconductors is to understand how the magnetic phase of the parent compounds evolves. Here we report the systematic investigation of paramagnetic to antiferromagnetic and tetragonal to orthorhombic structural transitions of “122” SrFe 2 As 2 parent compound using combined high resolution synchrotron Mössbauer spectroscopy and x-ray diffraction techniques in a cryogenically cooled high pressure diamond anvil cell. It is found that although the two transitions are coupled at 205 K at ambient pressure, they are concurrently suppressed to much lower temperatures near a quantum critical pressure of approximately 4.8 GPa where the antiferromagnetic state transforms into bulk superconducting state. Our results indicate that the lattice distortions and magnetism jointly play a critical role in inducing superconductivity in iron based compounds.

We compare two commonly used procedures, namely, the iterative rank-dependent reordering (IRDR) procedure and the translation process based procedure, for simulating homogeneous/nonhomogeneous non-Gaussian fields. We identify the limitations and the implicit assumptions of the procedures. We provide a new interpretation of the IRDR procedure, point out that there is no guarantee that the algorithm converges, and suggest modifications in terms of the initial samples, iteration involving decomposition, and convergence requirement to the IRDR procedure for it to become more efficient and robust. The numerical results show that, depending on the prescribed marginal probability distribution, the use of the IRDR procedure may not achieve a prescribed correlation function, a feature that is well-known if the translation process (i.e., Nataf translation system) based procedure is employed. It is shown that the performance of the modified IRDR procedure is comparable to that of the translation process based procedures in terms of limitations and matching the prescribed correlation function. The numerical results also show that the suggested modifications to IRDR in the present study make the algorithm more efficient and robust.

Investigating the stress redistribution characteristics after tunneling is critical for designing and constructing deeply buried tunnels. Three-dimensional stresses are more prominent in deep than in shallow tunnels, resulting in nonlinear strength. The generalized Zhang–Zhu (GZZ) criterion captures the nonlinear strength well. Therefore, this study established a 2D plane-strain numerical model using a GZZ-based constitutive model. The effects of the axial stress and rock properties on the stress redistribution and plastic zone are discussed. The initial axial stresses changed the axial stress distribution after excavation and had little effect on the radial and tangential stress distributions. The size of the plastic zone decreases with decreasing geological strength index and increasing rock mass m i . However, with increasing dilation coefficient, the stress distributions remained almost unchanged, whereas the radial deformation gradually increased.

The feasibility of thermal pressure ventilation technology for ventilation and cooling of extra long construction tunnel with high altitude and high ground temperature was discussed. A physical model was built with a proportional factor of 1:1 based on the design documents of Zilashan tunnel in China. The CFD model considering buoyancy effects was used to evaluated the influence of the initial rock temperature, the insulation performance of the left tunnel and the outdoor air temperature on the effect of thermal pressure ventilation. Results show that the effect of thermal pressure ventilation increases by 12.2%, and the effect of cooling enhances by 3.7% when the left tunnel has no insulation. Compared with the initial rock temperature, the outdoor air temperature has a greater influence on thermal pressure ventilation. When the initial rock temperature is below 54 °C, outdoor air temperature is below 17.5 °C and the left tunnel has no insulation, thermal pressure ventilation technology is feasible for ventilation and cooling of Zilashan tunnel with a shaft of 450 m height. The thermal pressure ventilation technology provides a reference for other construction tunnel projects as a design of ventilation and cooling.

Underground excavation would cause two main excavation effects: (1) stress redistribution, including radial stress decrease and tangential stress concentration; and (2) surrounding rock degradation. Comprehensive consideration of excavation effects is crucial to prevent underground engineering disasters. However, the two excavation effects are not considered in the predominantly used Platts pressure arch theory, whereas the New Austrian tunneling method is focused on the full utilization of the strength of the surrounding rock. Construction designing using these methods could lead to disaster deep underground. Thus, in this study, the stress control method (SCM) was proposed to comprehensively consider the two excavation effects. The following two key SCM principles were introduced in this study: (1) adopt the largest possible prestressing force to increase the low radial stress caused by excavation; (2) timing of support should be as early as possible to minimize surrounding rock deterioration. The application principles of SCM in hard rock tunnels and soft rock tunnels are explained

The aim of this research is to study the effect of the controlled releasing character of the salmon calcitonin (S-CT) loaded injectable calcium phosphate cement (CPC) modified by adding organic phase, chitosan oligosaccharide (CO) and collagen polypeptide (CP). The uniform design was used to determine the basic formulation with suitable injectable time for clinical application, and then the changes of the physical characters, the controlled releasing character of the modified CPC along with the ratio of the organic phase were also evaluated in vitro. The surface morphous of the modified CPC been implanted in the abdominal cavity or soaked into the serum of rat was also observed by scanning electron microscope (SEM). The result shows that a suitable formulation of modified CPC could be got, and the injectable time is 12 min, the compressive strength is 12 MPa, and the final setting time is 40 min. Comparing with the CPC without organic phase, the releasing rate of S-CT would increase along with the increase of the organic phase after 7th day. Therefore, a novel S-CT loaded bioactive injectable CPC for treating osteoporosis induced bone defect was obtained, and the release of the containing S-CT was controlled easily through adjusting the ratio of CO and CP.