59 research outputs found

    BPTF promotes tumor growth and predicts poor prognosis in lung adenocarcinomas.

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    BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers

    Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

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    Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

    The diploid genome sequence of an Asian individual

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    Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics

    A HIGH-FIDELITY SIMULATION OF THE C5G7 BENCHMARK BY USING THE PARALLEL ENTER CODE

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    In simulation of advanced nuclear reactors, requirements like high precision, high efficiency and convenient to multi-physics coupling are putting forward. The deterministic transport method has the advantage of high efficiency, capable of obtaining detailed flux distribution and efficient in multi-physics coupling, but its accuracy is limited by the homogenized reaction cross-section data and core modelling exactness. The traditional two-steps homogenization strategy may introduce substantial deviation during the assembly calculation. It is possible to conduct a whole core deterministic transport simulation pin-by-pin to achieve higher accuracy, which eliminates the assembly homogenization process. The C5G7 benchmarks were proposed to test the ability of a modern deterministic transport code in analyzing whole core reactor problems without spatial homogenization. Different deterministic code that developed by different methods were applied to the benchmark simulation and some of them solved the benchmark accurately. However, there still exist some drawbacks in the given calculation processes which carried out by some other deterministic transport codes and we could find that the fuel pin cell in the assembly were not exactly geometrically modelled owing to the limit of the code. Consequently, the calculation precision could be improved by utilizing a high-fidelity geometry modelling. In this paper, the C5G7 benchmarks with different control rod position and different configuration were calculated by the finite element SN neutron transport code ENTER [1], and the results were presented after massively parallel computation on TIANHE-II supercomputer. By introducing a large scale high-fidelity unstructured meshes, high fidelity distributions of power and neutron flux were gained and compared with the results from other codes, excellent consistency were observed. To sum up, the ENTER code can meet those new requirements in simulation of advanced nuclear reactors and more works and researches will be implemented for a further improvement

    Coded pinhole lens imaging

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    This paper presents a coded pinhole lens imaging system consisting of a pinhole array aperture, followed by a thin convex lens, mounted onto a standard DSLR camera body. The combination of pinhole and lens incurs two questions: (1) Is the new camera based on pinhole or lens imaging principle? (2) Can the lens improve the imaging quality? The study reveals that the camera is based on pinhole imaging, but the lens can improve its optical resolution from 0.44 mm (pinhole size) to 0.042 mm, leading to a significant improvement in imaging quality. The numerous pinholes on the aperture also improve the cameras light throughput ability over single pinhole camera. The camera could be used for applications where a large depth of field is required while the illumination condition is poor

    Aluminium-carbon nanotubes composites produced from friction stir processing and selective laser melting

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    Aluminium reinforced with multi-wall carbon nanotubes was produced using friction stir processing and selective laser melting. Very fine grains were successfully achieved in both methods with high Vickers hardness values. Cavities were present in selective laser melting of AlSi10Mg reinforced with multi-wall carbon nanotubes parts resulting in higher stress concentration brittle fracture appearance. The high laser absorption and higher thermal conductivity of multi-wall carbon nanotubes resulted in the formation of the cavities in the melted parts. However, the fractography images showed dimpled like appearance indicating a ductile fracture mechanism. Multi-wall carbon nanotubes were observed at the fracture sites indicating the presence of a crack-bridging mechanism. In comparison to carbon nanotubes reinforced aluminium by friction stir processing, selective laser melting produces aluminium reinforced aluminium with better mechanical properties.Accepted versio

    Friction stir processing of Al-CNT composites

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    Friction stir processing (FSP) is a solid-state process with the ability to refine grain sizes and uniformly disperse particles to improve the mechanical properties of the base material. In this study, FSP was performed on AA6061-T6 with and without additions of multi-walled CNTs. For FSP on monolithic Al plates, dendrites were broken down and dispersed uniformly with the increase in number of passes. As for FSP of Al–CNT composites, the CNTs have been successfully dispersed with three FSP passes. Dispersion is more uniform with increasing number of passes. The Vickers hardness and tensile yield strength were found to have improved after performing FSP with the addition of CNT as compared to FSP of AA6061-T6 without CNT.Accepted versio
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