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Öğe Association of MicroRNA 211 expression with prognosis in colorectal cancer: A case-control study(Lippincott Williams & Wilkins, 2014) Sumbul, Ahmet Taner; Gogebakan, Bulent; Oztuzcu, Serdar; Yengil, Erhan; Sezer, Ahmet; Aball, Huseyin[Abstract Not Available]Öğe The cell fate: senescence or quiescence(Springer, 2016) Terzi, Menderes Yusuf; Izmirli, Muzeyyen; Gogebakan, BulentSenescence and quiescence are frequently used as interchangeable terms in the literature unwittingly. Despite the fact that common molecules play role in decision of cell cycle arrest, senescent and quiescent cells have some distinctive phenotypes at both molecular and morphological levels. Thus, in this review we summarized the features of senescence and quiescence with respect to visual characteristics and prominent key molecules. A PubMed research was conducted for the key words; senescence'', quiescence'' and cell cycle arrest''. The results which are related to cell cycle control were selected. The selection criteria of the target articles used for this review included also key cell cycle molecules such as p53, pRB, p21, p16, mTOR, p27, etc. The results were not evaluated statistically. The mechanistic target of rapamycin (mTOR) has been claimed to be key molecule in switching on/off senescence/quiescence. Specifically, although maximal p53 activation blocks mTOR and causes quiescence, partial p53 activation sustains mTOR activity and causes senescence subsequently. In broader perspective, quiescence occurs due to lack of nutrition and growth factors whereas senescence takes place due to aging and serious DNA damages. Contrary to quiescence, senescence is a degenerative process ensuing a certain cell death. We highlighted several differences between senescence and quiescence and their key molecules in this review. Whereas quiescence (cell cycle arrest) is only one half of the senescence, the other half is growth stimulation which causes actual senescence phenotype.Öğe CORRESPONDING ERDOSTEINE CHANGES AUTOPHAGY GENES EXPRESSION IN HIPPOCAMPUS ON RHINITIS MEDICAMENTOSA MODEL(Serbian Genetics Soc, 2015) Dokuyucu, Recep; Gogebakan, Bulent; Cevik, CengizIn our study, rats were subjected to Oxymetazoline hydrochloride treatment and Rhinitis medicamentosa (RM) was formed and then autophagy gene expression levels were determined after the application of an antioxidant agent erdosteine (ED). The rats were divided into three groups; Group 1 was the control group. Group 2 (RM) and group 3 (RM+ED) rats received two spray puffs of 0.05% oxymetazoline into the nasal cavities three times daily for eight weeks. After determination of RM in the rats, the RM group were killed. The ED+RM group received 10 mg/kg of an ED suspension. At the end of seven days, these rats were also killed. All groups' hippocampus tissues were obtained for the measurement of autophagy gene expressions. In rhinitis medicamentosa group Atg5, Atg7 and Atg10 gene expressions in the left hippocampus were reduced as compared to control group (p=0.01, p>0.05, p=0.01, respectively). Also, erdosteine treatments were restored mRNA expression of autophagy genes. In right hippocampus of rhinitis medicamentosa group, Atg5 and Atg10 gene expressions was found to be down-regulated as compared to control group (p>0.05, p<0.05, respectively). Both BECN1 and ULK genes expression were found to be reduced in left hippocampus of rhinitis medicamentosa group. Erdosteine applications was restored the expression of these genes (p=0.03, p=0.03, respectively). Additionally, in right hippocampus, Erdosteine application was restored the expression of ULK gene (p=0.01). This is the first report that evaluated the expression autophagy genes in RM rat models and the changes observed after erdosteine applications.Öğe Do Fasudil and Y-27632 affect the level of transient receptor potential (TRP) gene expressions in breast cancer cell lines?(Springer, 2014) Gogebakan, Bulent; Bayraktar, Recep; Suner, Ali; Balakan, Ozan; Ulasli, Mustafa; Izmirli, Muzeyyen; Oztuzcu, SerdarBreast cancer (BC) is the most frequent cancer type in women, and the mortality rate is high especially in metastatic disease. Ion channels such as the transient receptor potential (TRP) channels correlate with malignant growth and cancer progression. Hence, some authors have suggested that the expression levels of TRP channels may be used as a marker in the diagnosis and predicting the prognosis of BC. Also, in some recent studies, targeting TRP channels are suggested as a novel treatment strategy in BC. The aim of this study was to investigate the effect of two Rho-kinase (ROCK) inhibitors, fasudil and Y-27632, on the expression levels of TRP channel genes in breast cancer cell lines (ZR-75-1, MCF7, and MDA-MB-231) and breast epithelial cell line (hTERT-HME1). The expression levels of TRP genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that fasudil had reduced the TRPC1, TRPV2 expression levels in the ZR-75-1, MCF7, and MDA-MB-231 cell lines. On the other hand, fasudil and Y-27632 had reduced TRPM6 expression levels in all cell lines. Y-27632 increased the expression levels of TRPC7 in all cell lines. In conclusion, this is the first study demonstrating that the inhibition of ROCK pathway changes the expression levels of some TRP genes. Also, our study has firstly shown that the expression levels of the TRP genes which are suggested as a diagnostic and prognostic biomarker in BC, were changed with the treatment of fasudil and Y-27632.Öğe The Effect of Caffeic Acid Phenethyl Ester (CAPE) on TRPM 2, 8 Channels in Hepatic Ischemia-Reperfusion Model(Wiley-Blackwell, 2016) Dokuyucu, Recep; Dogan, Hatice; Tutuk, Okan; Sefil, Fatih; Gogebakan, Bulent; Gokce, Hasan; Tumer, Cemil[Abstract Not Available]Öğe The Effect of Erdosteine on Autophagy Genes Expression in Hippocampus on Rhinitis Medicamentosa Model(Wiley-Blackwell, 2015) Dokuyucu, Recep; Gogebakan, Bulent; Cevik, Cengiz[Abstract Not Available]Öğe Effect of GM-CSF levels on osteoporosis in postmenopausal period(Acta Medica Mediterranea, 2014) Yagiz, Abdullah Erman; Dokuyucu, Recep; Sumbul, Ahmet Taner; Yengil, Erhan; Ustun, Nilgul; Koca, Irfan; Gogebakan, BulentObjectives: Cytokines and hematopoietic growth factors may play a role in the pathogenesis of osteoporosis. The aim of this study was to assess the relationship between osteoporosis (OP) and granulocyte-macrophage colony stimulating factor (GM-CSF) in postmenopausal period. Materials and methods: Total number of 80 female patients between the ages of 45-75 and who had entered in menopause from at least one year and diagnosed with OP were enrolled in this study. As a control group, 80 healthy volunteer female patients who had entered in menopause from at least one year and had no diagnosis of OP were selected. The age, height, weight, body mass index, duration of menopause, exercise habits of the patients and controls were recorded and bone mineral density was measured for the diagnosis of OP. The serum GM-CSF concentrations of individuals were quantified using a specific enzyme immunoassay kit. Results: There was no significant relationship between the mean age, duration of menopause and body mass index of patients and controls (p>0.05). Serum GM-CSF levels of patients and control groups did not differ significantly (p> 0.05). Conclusion: The results of our study showed that there was no significant correlation between osteoporosis and serum GMCSF levels. Osteoporosis might be correlating with the levels of GM-CSF in bone microenvironment rather than serum levels.Öğe EFFECT OF GM-CSF LEVELS ON OSTEOPOROSIS IN POSTMENOPAUSAL PERIOD(Carbone Editore, 2014) Yagiz, Abdullah Erman; Dokuyucu, Recep; Sumbul, Ahmet Taner; Yengil, Erhan; Ustun, Nilgul; Koca, Irfan; Gogebakan, BulentObjectives: Cytokines and hematopoietic growth factors may play a role in the pathogenesis of osteoporosis. The aim of this study was to assess the relationship between osteoporosis (OP) and granulocyte-macrophage colony stimulating factor (GM-CSF) in postmenopausal period. Materials and methods: Total number of 80 female patients between the ages of 45-75 and who had entered in menopause from at least one year and diagnosed with OP were enrolled in this study. As a control group, 80 healthy volunteer female patients who had entered in menopause from at least one year and had no diagnosis of OP were selected. The age, height, weight, body mass index, duration of menopause, exercise habits of the patients and controls were recorded and bone mineral density was measured for the diagnosis of OP. The serum GM-CSF concentrations of individuals were quantified using a specific enzyme immunoassay kit. Results: There was no significant relationship between the mean age, duration of menopause and body mass index of patients and controls (p>0.05). Serum GM-CSF levels of patients and control groups did not differ significantly (p> 0.05). Conclusion: The results of our study showed that there was no significant correlation between osteoporosis and serum GMCSF levels. Osteoporosis might be correlating with the levels of GM-CSF in bone microenvironment rather than serum levels.Öğe Effects of Alpha-Lipoic Acid on Urotensin II and TGF-?1 on Steroid-induced Osteonecrosis in Rats(Wiley-Blackwell, 2016) Dokuyucu, Recep; Tutuk, Okan; Dogan, Hatice; Bilgic, Nilufer; Tas, Zeynel Abidin; Sefil, Fatih; Gogebakan, Bulent[Abstract Not Available]Öğe Effects of dexamethasone and anti-inflammatory drugs on inflammatory cytokines from bronchial epithelial cells of COPD patients(European Respiratory Soc Journals Ltd, 2015) Koc, Ibrahim; Gogebakan, Bulent; Bayraktar, Recep; Tasdemir, Demet; Ozdemir, Ufkun; Adcock, Ian; Bayram, Hasan[Abstract Not Available]Öğe The expression levels of the sirtuins in patients with BCC(Springer, 2016) Temel, Metin; Koc, Mustafa Nihat; Ulutas, Saffet; Gogebakan, BulentBasal cell carcinoma (BCC) is the most common tumor in humans. Reduced expression of sirtuins interferes with DNA repair, which may cause mutations and genomic instability, and eventually leads to tumor development. In the present study, we investigate the expression levels of SIRT genes in non-tumoral and tumor tissues of patients with BCC. A total of 27 patients (16 males, 11 females) with BCC were included in the study; the mean age was 65.40 +/- 10.74 years and mean follow-up was 2.5 +/- 0.5 years. There were multiple synchronous lesions in six patients, and the remaining 21 patients had a single lesion. Tumor and nontumoral tissue samples were collected from all patients, and mRNA expression levels of SIRT1-7 (Sirt1.1, Sirt1.2, Sirt2, Sirt3, Sirt4, Sirt5, Sirt6, and Sirt7) were examined by real-time PCR. The results showed that expressions of SIRT1.1, SIRT1.2, SIRT4, SIRT5, SIRT6, and SIRT7 mRNAs were unchanged in tumor tissues of BCC patients compared with non-tumoral tissue samples. Importantly, the expressions of SIRT2 and SIRT3 mRNAs were significantly reduced in tumor tissue samples from BCC patients compared with non-tumoral tissues (P=0.02 and P=0.03, respectively). In light of the previous reports that have demonstrated a link between SIRT proteins and cancer, our findings suggest that SIRT2 and SIRT3 may plan important roles in BCC pathogenesis and could be candidate prognostic biomarkers for BCC.Öğe Expressions of TRPM6 and TRPM7 and histopathological evaluation of tissues in ischemia reperfusion performed rats(Informa Healthcare, 2014) Dokuyucu, Recep; Gogebakan, Bulent; Yumrutas, Onder; Bozgeyik, Ibrahim; Gokce, Hasan; Demir, TuncerThere is very little work on the expression of TRPM6/7 in ischemia reperfusion models. In previous studies, after ischemia, reperfusion had been kept limited to 24 h, yet in our study, expressions of these channels were elucidated after its modification to 48 h to establish what kind of changes renal tissues undergo. For the current study, 20 Wistar albino rats were divided into two groups equally. Group I: control group, Group II = I/R group (60 min ischemia + 48 h reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a reference in order to eliminate genetic differences. The left renal artery (I/R generated part) of I/R area was removed from all rats in the second group. Likewise, normal tissues of right renal artery were removed from all rats. Histopathologic scoring of the tissue samples were achieved semi-quantitatively according to normal tissue composition. Consequently, both TRPM6 and TRPM7 expression levels were decreased in all groups according to control groups, yet results were not counted as significant (p>0.05). Additionally, correlation analysis confirmed these results. Also, I/R performed kidneys had more tissue damage compared to control group. To conclude, our study results suggest that TRPM6/7 expressions may be increased and after 48 h of reperfusion expression levels of these two stored to normal levels. At the same time, damages have occurred in renal tissues after ischemia. These damages were considered to be resulted from the oxidative effects as previously reported.Öğe Investigation of the Effect of CAPE on Urotensin II and TGF-?1 Levels on Experimental Osteonecrosis Rat Model(Wiley-Blackwell, 2016) Dokuyucu, Recep; Tutuk, Okan; Gogebakan, Bulent; Dogan, Hatice; Bilgic, Nilufer; Tas, Zeynel Abidin; Sefil, Fatih[Abstract Not Available]Öğe Loss of heterozygosity of chromosome 13q33-34 region and molecular analysis of ING1 and p53 genes in bladder carcinoma(Springer, 2015) Igci, Mehri; Arslan, Ahmet; Erturhan, Sakip; Igci, Yusuf Ziya; Pala, Elif; Gogebakan, Bulent; Karakok, MetinCancer is a consequence of accumulation of genetic and epigenetic alterations in the cell which can lead to activation of oncogenes or inactivation of tumor suppressor genes (TSG). Since members of ING family were discovered as TSGs in different cancer types, it was aimed to analyze the chromosome 13q33-34 region, ING1 and p53 genes in bladder cancer. 30 paired normal and tumor tissues were investigated in terms of microdeletion of chromosome 13q33-34 region, ING1 expression and mutation status of ING1 and p53 genes. Because there is no data available about the transcription factors which bind to ING1 promoter, the promoter sequence was analyzed via Genomatix-MatInspector and TFSEARCH softwares. Used DS markers were D13S285, D13S1315, D13S796, D13S278, D13S158, and D13S779 where loss of heterozygosity (LOH) results were as 23.3, 20, 6.7, 3.3, 6.7, and 0 %, respectively. The highest LOH scores were obtained with markers D13S285 and D13S1315 which are flanking the ING1. Seven of 30 cases showed alteration in expression (p > 0.05). However, no mutation was detected in the exons of ING1. One patient showed a two-nucleotide deletion in p53 gene. However no significant TSG activity of ING1 was observed while higher activity was reported in different cancer types. As for the LOH data 13q33-34 region may contain different candidate TSGs like COL4A1, COL4A2 and SOX1. As a result of computational promoter analysis, some factors like ABL, E2F, HIF1, SOX, P53, BPTF, NRSF, c-Rel and c-ETS were associated with the promoter region. Molecular analysis of ING1 promoter warrants further analysis.Öğe Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in psoriasis in southern Turkey(Soc Brasileira Dermatologia, 2016) Izmirli, Muzeyyen; Sen, Bilge Bulbul; Rifaioglu, Eminenur; Gogebakan, Bulent; Aldemir, Ozgur; Sen, Tuba; Ekiz, OzlemBackground: Psoriasis is a multigenic and multifactorial dermatological disease linked to cardiovascular diseases. Increased levels of homocysteine in patients with psoriasis have been demonstrated in many studies. The most frequently investigated genetic defect that plays a role in homocysteine metabolism is single point substitution (C to T) located on the 677th nucleotide of the methylenetetrahydrofolate reductase gene (MTHFR). Objective: In this study, we aimed to investigate methylenetetrahydrofolate C677T polymorphism in psoriasis patients in Turkey. Methods: The study included 96 patients with psoriasis and 77 controls from southern Turkey. Methylenetetrahydrofolate C677T polymorphism was analysed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism methods. Results: In the psoriasis group, 34 CC (35.4%), 46 CT (47.9%) and 16 TT (16.7%) genotypes were found, respectively; while in the control group, the figures were 39 (50.6%), 35 (45.5%), 3 (3.9%). Homozygote and heterozygote T alleles of methylenetetrahydrofolate C677T polymorphism were significantly higher in the psoriasis than in the control group (p=0.013). Conclusion: We firstly found a correlation between methylenetetrahydrofolate C677T polymorphism and psoriasis among the southern Turkish population.Öğe MicroRNA 211 expression is upregulated and associated with poor prognosis in colorectal cancer: a case-control study(Sage Publications Ltd, 2015) Sumbul, Ahmet Taner; Gogebakan, Bulent; Bayram, Suleyman; Batmaci, Celal Yucel; Oztuzcu, SerdarIncreasingly more evidence support the role of the microRNAs (miRNA) in tumorigenesis. The role of up/downregulation microRNA-211 (miR-211) during human tumorigenesis is still contentious and may exhibit tissue-specific regulatory manner, but the exhaustive mechanisms underlying its pro/anti-oncogenic effects remain to be unknown. Sixty-six patients that were diagnosed and operated with colorectal cancer (CRC) and sixty-five healthy cases that were age and sex compatible with them were included in our study. miRNA was isolated from the formalin-fixed paraffin-embedded (FFPE) tissues of all cases. The expression level of miR-211 in matched normal and tumor tissues of CRC group and healthy group was evaluated using a quantitative real-time RT-PCR (qRT-PCR). Based on the average miR-211 levels, two groups of low or high expression were formed in CRC group. Correlation of the patients' clinicopathological factors and survival was also analyzed. No statistically significant differences were found in miR-211 levels among tumorous and normal tissues of CRC patient group (P = 0.59). Also, no statistically significant correlation was determined between clinicopathological factors and miR-211 expression level in CRC group. However, miR-211 expression levels between the CRC group and the healthy group were determined to be of statistical significance (P < 0.0001). There were 33 (50 %) CRC patients that expressed low levels of miR-211 and 33 (50 %) CRC patients that expressed high levels of miR-211. A median survival between low levels of miR-211 group and high levels of miR-211 group was evaluated via Kaplan-Meier, and the difference was of statistical significance (P = 0.035). The univariate analysis of the factors that may affect survival indicated invasion depth (P = 0.063), lymphovascular invasion (P = 0.011), perineural invasion (P = 0.009), and miR-211 expression level (P = 0.041) presence to be effective. In the multivariate analysis of these factors with overall survival, only miR-211 expression level (P = 0.01) was effective on overall survival. Our results suggest for the first time that miR-211 expressed more in CRC patients than in healthy group could be a new prognostic biomarker in order to predict survival. Independent studies are needed to validate our findings in a larger series, as well as in cancer of different tissues.Öğe miR-204-5p expression in colorectal cancer: an autophagy-associated gene(Sage Publications Ltd, 2014) Sumbul, Ahmet Taner; Gogebakan, Bulent; Ergun, Sercan; Yengil, Erhan; Batmaci, Celal Yucel; Tonyali, Onder; Yaldiz, MehmetMicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low-and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p=0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p=0.021 and p=0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-2045p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p=0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.Öğe Thr21Met (T21M) but not Ser89Asn (S89N) polymorphisms of the urotensin-II (UTS-II) gene are associated with Behcet's disease (BD)(Elsevier Science Inc, 2013) Oztuzcu, Serdar; Ulasli, Mustafa; Pehlivan, Yavuz; Cevik, Muhammer Ozgur; Cengiz, Beyhan; Gogebakan, Bulent; Igci, Yusuf ZiyaBehcet's disease (BD) is multisytemic vasculitis or chronic inflammation that may lead to various autoimmune and autoinflammatory syndromes. Exact etiopathogenesis of BD has not been clarified yet. Urotensin II (UTS-II) is predominantly a vasoactive peptide and Thr21Met polymorphism in UTS-II gene was proved to increasing in some autoimmune diseases. Considering these, our objective was to evaluate whether two UTS-II gene polymorphisms (Thr21Met and Ser89Asn) were responsible in genetic susceptibility to BD in a Turkish population. A total of 198 patients with BD and 275 healthy controls were enrolled. We analyzed the genotype and allele frequencies of two UTS-II gene polymorphisms, Thr21Met and Ser89Asn, in BD patients and in controls. We found that Thr21Met but not Ser89Asn polymorphisms of the UTS-II gene were markedly associated with the risk of developing BD (p<0.0001), The Met21Met genotype was less common among BD patients (6.1% in patients vs. 17.1% in controls; p<0.0001). There was also an increase in the 21Thr allele (54.8% in BD patients vs. 43.8% in controls) and a decrease in 21Met allele frequencies (45.2% in controls vs. 56.2% in patients) in the BD groups (p<0.0044). To the best of our knowledge, for the first time in the literature, our study claims that there is an association between Thr21Met, and not between Ser89Asn polymorphisms in the UTS-II gene and BD. These results put a new player to the field of undiscovered pathogenesis of BD and hopefully provide new insights to the treatment options. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.Öğe Urotensin II (U-II), a novel cyclic peptide, possibly associated with the pathophysiology of osteoarthritis(Elsevier Science Inc, 2014) Gogebakan, Bulent; Uruc, Vedat; Ozden, Raif; Duman, Ibrahim Gokhan; Yagiz, Abdullah Erman; Okuyan, Hamza Malik; Aldemir, OzgurSynovial fibrosis is one of the main outcomes of osteoarthritis. Some authors have reported that urotensinII (U-II) may cause pathologic fibrosis in cardiovascular system, lung and liver. However there are no previous reports available in the literature about its relationship with the synovial fibrosis in osteoarthritis. The aim of this study was to compare the U-II levels in knee synovial fluids obtained from osteoarthritic and non-osteoarthritic patients. Two groups were created, the osteoarthritis group and non-osteoarthritic control group. The control group was consisted of patients who underwent arthroscopic surgery for other reasons than cartilage disorders. In the osteoarthritis group all patients had grade 4 primer degenerative osteoarthritis and were treated with total knee arthroplasty. Minimum 1 mL knee synovial fluids were obtained during operation. Levels of U-II were measured by using ELISA kit U-II levels were significantly higher in the osteoarthritic group than that in the control group. No correlation was found between U-II levels and age. In conclusion, the significantly high U-II levels in the knee synovial fluid of osteoarthritic patients supported our hypothesis that U-II may be associated with the synovial fibrosis in osteoarthritis.(c) 2014 Elsevier Inc. All rights reserved.
