Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become “immortal”) by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism.
Watermarking is identified as a major technology to achieve copyright protection and multimedia security. Therefore, recent studies in literature include some evident approaches for embedding data into a multimedia element. Because of its useful frequency component separation, the Discrete Wavelet Transform (DWT) is commonly used in watermarking schemes. In a DWT-based scheme, the DWT coefficients are modified with the data that represents the watermark. In this paper, we present a hybrid non-blind scheme based on DWT and Singular Value Decomposition (SVD). After decomposing the cover image into four sub bands (LL, HL, LH and HH), we apply the SVD to LL band and modify diagonal singular value coefficients with the watermark itself by using a scaling factor. Finally, LL band coefficients are reconstructed with modified singular values and inverse DWT is applied to obtain watermarked image. Experimental results show that the proposed algorithm is considerably robust and reliable. In comparison to the previous literature, peak signal-to-noise ratio (PSNR) values of watermarked images are increased by approximately 20%. In terms of PSNR values before and after attacks and of normalized similarity ratio (NSR); although watermark is embedded into LL sub band; our proposed method gives much more satisfactory results on filtering, scaling, Gaussian, JPEG compression, rotation and cropping than that of previous literature.
This work highlights the characteristics of an experimental outdoor free space optical (FSO) communication system combined with a redundant radio frequency (RF) link that provides high availability and uninterrupted communication even in adverse weather conditions. The system provides wireless connection between the two of the five campuses of Ankara University. The rationale behind the selection of design parameters is given and the structure of the hybrid system is outlined. Results, regarding the link availability of the system, which has been operational for over 2 years, are presented.
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