Browsing by Author "Atalay, R."
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Item Open Access Application of data mining techniques to protein-protein interaction prediction(Springer-Verlag Berlin, 2003) Kocatas, A.; Gursoy, A.; Atalay, R.Protein-protein interactions are key to understanding biological processes and disease mechanisms in organisms. There is a vast amount of data on proteins waiting to be explored. In this paper, we describe application of data mining techniques, namely association rule mining and ID3 classification, to the problem of predicting protein-protein interactions. We have combined available interaction data and protein domain decomposition data to infer new interactions. Preliminary results show that our approach helps us find plausible rules to understand biological processes. © Springer-Verlag Berlin Heidelberg 2003.Item Open Access Bi-k-bi clustering: mining large scale gene expression data using two-level biclustering(Inderscience Enterprises Ltd., 2010) Çarkacioǧlu, L.; Atalay, R.; Konu, O.; Atalay, V.; Can, T.Due to the increase in gene expression data sets in recent years, various data mining techniques have been proposed for mining gene expression profiles. However, most of these methods target single gene expression data sets and cannot handle all the available gene expression data in public databases in reasonable amount of time and space. In this paper, we propose a novel framework, bi-k-bi clustering, for finding association rules of gene pairs that can easily operate on large scale and multiple heterogeneous data sets. We applied our proposed framework on the available NCBI GEO Homo sapiens data sets. Our results show consistency and relatedness with the available literature and also provides novel associations. Copyright © 2010 Inderscience Enterprises Ltd.Item Open Access Cancer cell Cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl) piperazine derivatives(M D P I AG, 2012) Yarim, M.; Koksal, M.; Durmaz, I.; Atalay, R.A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a-g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and 1H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compound. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines. © 2012 by the authors; licensee MDPI, Basel, Switzerland.Item Open Access CD8 lineage-specific regulation of interleukin-7 receptor expression by the transcriptional repressor Gfi1(The American Society for Biochemistry and Molecular Biology, Inc., 2012) Ligons, D. L.; Tuncer, C.; Linowes, B. A.; Akcay, I. M.; Kurtulus, S.; Deniz, E.; Arslan, B. A.; Cevik, S. I.; Keller, H. R.; Luckey, M. A.; Feigenbaum, L.; Möröy, T.; Ersahin, T.; Atalay, R.; Erman, B.; Park, J. H.Interleukin-7 receptor α (IL-7Rα) is essential for T cell survival and differentiation. Glucocorticoids are potent enhancers of IL-7Rα expression with diverse roles in T cell biology. Here we identify the transcriptional repressor, growth factor independent-1 (Gfi1), as a novel intermediary in glucocorticoid-induced IL-7Rα up-regulation. We found Gfi1 to be a major inhibitory target of dexamethasone by microarray expression profiling of 3B4.15 T-hybridoma cells. Concordantly, retroviral transduction of Gfi1 significantly blunted IL-7Rα up-regulation by dexamethasone. To further assess the role of Gfi1 in vivo, we generated bacterial artificial chromosome (BAC) transgenic mice, in which a modified Il7r locus expresses GFP to report Il7r gene transcription. By introducing this BAC reporter transgene into either Gfi1-deficient or Gfi1-transgenic mice, we document in vivo that IL-7Rα transcription is up-regulated in the absence of Gfi1 and down-regulated when Gfi1 is overexpressed. Strikingly, the in vivo regulatory role of Gfi1 was specific for CD8+, and not CD4+ T cells or immature thymocytes. These results identify Gfi1 as a specific transcriptional repressor of the Il7r gene in CD8 T lymphocytes in vivo.Item Open Access Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors(Elsevier, 2016) Şenkardeş, S.; Kaushik-Basu, N.; Durmaz, İrem; Manvar, D.; Basu, A.; Atalay, R.; Küçükgüzel, Ş. GünizHepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. We have previously identified the hydrazideehydrazone scaffold as a promising hepatitis C virus (HCV) and hepatocelluler inhibitor. Herein we describe the design a number of 20,40-difluoro-4-hydroxy-N'-(arylmethylidene) biphenyl-3-carbohydrazide (3a-t) as anti-HCV and anticancer agents. Results from evaluation of anti-HCV activity indicated that most of the synthesized hydrazone derivatives inhibited viral replication in the Huh7/Rep-Feo1b and Huh 7.5-FGR-JCI-Rluc2A reporter systems. Antiproliferative activities of increasing concentrations of 20,40-difluoro-4-hydroxy-N'-(2-pyridyl methylidene)biphenyl-3-carbohydrazide 3b and diflunisal (2.5e40 μM) were assessed in liver cancer cell lines (Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475) with sulforhodamine B assay for 72 h. Compound 3b with 2-pyridinyl group in the hydrazone part exhibited promising cytotoxic activity against all cell lines with IC50 values of 10, 10.34 16.21 4.74, 9.29 and 8.33 μM for Huh7, HepG2, Hep3B, Mahlavu, FOCUS and SNU-475 cells, respectively, and produced dramatic cell cycle arrest at SubG1/G0 phase as an indicator of apoptotic cell death induction.