Akademik Çıktılar

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Citation Count: 9
Developing polymer composite-based leaf spring systems for automotive industry
(Walter de Gruyter Gmbh, 2018) Oztoprak, Nahit; Gunes, Mehmet Deniz; Tanoglu, Metin; Aktas, Engin; Egilmez, Oguz Ozgur; Senocak, Ciler; Kulac, Gediz; Tanoğlu, Metin
Composite-based mono-leaf spring systems were designed and manufactured to replace existing mono-leaf metal leaf spring in a light commercial vehicle. In this study, experimentally obtained mechanical properties of different fiber-reinforced polymer materials are presented first, followed by the description of the finite element analytical model created in Abaqus 6.12-1 (Dassault Systemes Simulia Corp., RI, US) using the obtained properties. The results from the finite element analysis are presented next and compared with actual size experimental tests conducted on manufactured prototypes. The results demonstrated that the reinforcement type and orientation dramatically influenced the spring rate. The prototypes showed significant weight reduction of about 80% with improved mechanical properties. The hybrid composite systems can be utilized for composite-based leaf springs with considerable mechanical performance.
Citation Count: 6
Docetaxel enhances the cytotoxic effects of imatinib on Philadelphia positive human chronic myeloid leukemia cells
(Taylor & Francis Ltd, 2009) Gucluler, Gozde; Baran, Yusuf; Baran, Yusuf
Chronic myelogenous leukemia (CML) results from a translocation between chromosomes 9 and 22 which generates BCR/ABL fusion protein and characterized by uncontrolled proliferation of immature white blood cells. Imatinib, a molecularly targeting anticancer agent, is used widely for the treatment of CML and showed significant activity in chronic and accelerated phases but much less in blast crisis phase. The resistance to imatinib especially in blast crisis phase is recognized as a major problem in the treatment of CML patients. Docetaxel is shown to arrest cells in G2/M phase of the cell cycle which makes cells more sensitive to chemo- and radiotherapy. In this study, we aimed to increase chemosensitivity of human K562 CML cells to imatinib in combination with docetaxel. Taken together, our results showed that the combination of imatinib and docetaxel decreased cellular proliferation and increased apoptosis in human K562 chronic myeloid leukemia cells as compared to any agent alone. Imatinib and docetaxel induced apoptosis through caspase-3 enzyme activity and mitochondrial membrane potential.
Citation Count: 35
Imatinib induces autophagy through BECLIN-1 and ATG5 genes in chronic myeloid leukemia cells
(Taylor & Francis Ltd, 2011) Can, Geylani; Ekiz, Huseyin Atakan; Baran, Yusuf; Baran, Yusuf
Imatinib is a chemotherapeutic drug used for the treatment of chronic myeloid leukemia (CML). Recent data showed imatinib-induced cell death in various types of cancers. Autophagy is the physiological process in which cellular components are broken down by the lysosomal activation. In this study, we aimed to examine the effects of imatinib on autophagy in addition to apoptosis in CML cells. Results suggested that imatinib induces autophagy in CML cells through inducing over-expression of BECLIN-1 and ATG5 genes with the statistical significance. Our results demonstrated that autophagy might be involved in imatinib-induced cell death.
Citation Count: 6
Input Contract Testing of Graphical User Interfaces
(World Scientific Publ Co Pte Ltd, 2016) Tuglular, Tugkan; Belli, Fevzi; Linschulte, Michael; Tuğlular, Tuğkan; Bilgisayar Mühendisliği Bölümü
User inputs are critical for the security, safety, and reliability of software systems. This paper proposes a new concept called user input contracts, which is an integral part of a design-by-contract supplemented development process, and a model-based testing approach to detect violations of user input contracts. The approach generates test cases from an input contract integrated with graph-based model of user interface specification and applies them to the system under consideration. The paper presents a proof-of-concept tool that has been developed and used to validate the approach by experiments. The experiments are conducted on a web-based system for marketing tourist services to analyze input robustness of system under consideration with respect to user input contracts.
Citation Count: 38
Mechanisms of cellular resistance to imatinib in human chronic myeloid leukemia cells
(Taylor & Francis Ltd, 2007) Baran, Yusuf; Ural, Ali Ugur; Gunduz, Ufuk; Baran, Yusuf
A major advancement in the treatment of chronic myeloid leukemia (CML) has been the development of imatinib, which has shown striking activity in the chronic phase and the accelerated phase, but less so in the blast phase of the disease. Despite high rates of hematologic and cytogenetic responses to therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of patients with CML. Various cellular mechanisms may be involved in the nature of cellular resistance. Increased amount of target, alteration in structure of target proteins, decreased drug uptake and increased detoxification are well-known mechanisms of resistance. On the other hand, in some cases, even if anticancer drugs reach their sites of action, bypassing drug efflux system of the cells, some cells still may survive via the dysregulation of apoptotic signalling. In this study, mechanisms of resistance to imatinib-induced apoptosis in human Meg-01 CML cells were examined. Continuous exposure of cells to step-wise increasing concentrations of imatinib resulted in the selection of 200- and 1000 nM imatinib-resistant sub-lines referred to as Meg-01/IMA-0,2 and Meg-01/1MA-1, respectively. MTT cell proliferation, cell cycle analyses and trypan blue dye exclusion analyses showed that Meg-0l/IMA-1 cells were resistant to imatinib-induced apoptosis as compared to parental sensitive cells. There was an increased expression of BCR/ABL, Bcl-2 and an increase in mitochondrial membrane potential (MMP) detected in resistant cells comparing to parental sensitive cells. There was no mutation detected in imatinib binding site of ABL kinase region. Various diverse mechanisms have been reported for their involvement in the multidrug resistance. In this study, it has been shown that the degree of BCR/ABL expression appears to be directly proportional to the levels of imatinib resistance. In addition, there have been BCR/ABL-independent mechanisms reported for deriving resistance against imatinib. Our results revealed that besides BCR/ABL overexpression, imatinib resistance also depends on the inhibition of apoptosis as a result of up-regulation of anti-apoptotic stimuli and down-regulation of pro-apoptotic stimuli through MMP but does not depend on any mutation on imatinib binding site of ABL kinase.
Citation Count: 45
Model-based mutation testing-Approach and case studies
(Elsevier, 2016) Belli, Fevzi; Budnik, Christof J.; Hollmann, Axel; Tuglular, Tugkan; Wong, W. Eric; Tuğlular, Tuğkan; Bilgisayar Mühendisliği Bölümü
This paper rigorously introduces the concept of model-based mutation testing (MBMT) and positions it in the landscape of mutation testing. Two elementary mutation operators, insertion and omission, are exemplarily applied to a hierarchy of graph-based models of increasing expressive power including directed graphs, event sequence graphs, finite-state machines and statecharts. Test cases generated based on the mutated models (mutants) are used to determine not only whether each mutant can be killed but also whether there are any faults in the corresponding system under consideration (SUC) developed based on the original model. Novelties of our approach are: (1) evaluation of the fault detection capability (in terms of revealing faults in the SUC) of test sets generated based on the mutated models, and (2) superseding of the great variety of existing mutation operators by iterations and combinations of the two proposed elementary operators. Three case studies were conducted on industrial and commercial real-life systems to demonstrate the feasibility of using the proposed MBMT approach in detecting faults in SUC, and to analyze its characteristic features. Our experimental data suggest that test sets generated based on the mutated models created by insertion operators are more effective in revealing faults in SUC than those generated by omission operators. Worth noting is that test sets following the MBMT approach were able to detect faults in the systems that were tested by manufacturers and independent testing organizations before they were released. (C) 2016 Elsevier B.V. All rights reserved.
Citation Count: 25
Multidrug Resistance Mediated by MRP1 Gene Overexpression in Breast Cancer Patients
(Taylor & Francis inc, 2009) Abaan, Ogan Demir; Mutlu, Pelin Kaya; Baran, Yusuf; Atalay, Can; Gunduz, Ufuk; Baran, Yusuf
Multidrug resistance (MDR) is a serious handicap towards the effective treatment of breast cancer patients. One of the most prevalent MDR mechanisms is through the overexpression of genes coding the proteins called Multidrug Resistance-associated Proteins (MRPs). The aim of this study was to investigate the expression of MRP1 in tumor tissues from breast cancer patients. In this study, a semi-quantitative RT-PCR approach was utilized. Our results suggest that MRP1 overexpression can mediate MDR in patients. Pre-evaluation of the level of such MDR mediators before chemotherapy can increase the efficacy of the treatment.
Citation Count: 0
Mutation-Based Minimal Test Suite Generation for Boolean Expressions
(World Scientific Publ Co Pte Ltd, 2023) Ayav, Tolga; Belli, Fevzi; Ayav, Tolga; Bilgisayar Mühendisliği Bölümü
Boolean expressions are highly involved in control flows of programs and software specifications. Coverage criteria for Boolean expressions aim at producing minimal test suites to detect software faults. There exist various testing criteria, efficiency of which is usually evaluated through mutation analysis. This paper proposes an integer programming-based minimal test suite generation technique relying on mutation analysis. The proposed technique also takes into account the cost of fault detection. The technique is optimal such that the resulting test suite guarantees to detect all the mutants under given fault assumptions, while maximizing the average percentage of fault detection of a test suite. Therefore, the approach presented can also be considered as a reference method to check the efficiency of any common technique. The method is evaluated using four well-known real benchmark sets of Boolean expressions and is also exemplary compared with MCDC criterion. The results show that the test suites generated by the proposed method provide better fault coverage values and faster fault detection.
Citation Count: 7
Nilotinib significantly induces apoptosis in imatinib resistant K562 cells with wild-type BCR-ABL, as effectively as in parental sensitive counterparts
(Taylor & Francis Ltd, 2010) Ekiz, Huseyin Atakan; Can, Geylani; Gunduz, Ufuk; Baran, Yusuf; Baran, Yusuf
Chronic myeloid leukemia (CML) is a hematological malignancy characterized by high levels of immature white blood cells. CML is caused by the translocation between chromosomes 9 and 22 (which results in the formation of the Philadelphia chromosome) creating BCR-ABL fusion protein. Imatinib and nilotinib are chemotherapeutic drugs which specifically bind to the BCR-ABL and inhibit cancer cells. Nilotinib is more effective in this respect than imatinib. We have shown that nilotinib induces apoptosis in imatinib-resistant K562 CML cells which have the wild-type BCR-ABL fusion gene almost to the same extent as it does in the parental sensitive cells by the increase in caspase-3 enzyme activity and the decrease in mitochondrial membrane potential. This effect of nilotinib, even in low concentrations, may indicate the efficacy of the usage of nilotinib in imatinib-resistant CML with less risk of undesired cytotoxic effects in the remaining cells of the body.
Citation Count: 29
Quercetin-induced apoptosis involves increased hTERT enzyme activity of leukemic cells
(Taylor & Francis Ltd, 2011) Avci, Cigir Biray; Yilmaz, Sunde; Dogan, Zeynep Ozlem; Saydam, Guray; Dodurga, Yavuz; Ekiz, Huseyin Atakan; Gunduz, Cumhur
We aimed to examine the growth suppressive effects of quercetin on acute promyelocytic and lymphoblastic leukemia and chronic myeloid leukemia, and to find out whether the growth suppression is related to the blocking of telomerase enzyme activity. Cytotoxic effects of quercetin were shown by trypan blue analyses. Apoptotic effects of quercetin were examined by acridine orange and ethidium bromide staining by fluorescence microscopy. The effects of quercetin on telomerase enzyme activity were shown by hTERT Quantification Kit. Our results demonstrated that quercetin has antiproliferative and apoptotic effects on T-cell acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia, and chronic myeloid leukemia (CML) cells. We also showed for the first time by this study that quercetin suppresses the activity of telomerase in ALL and CML cells. The results of this study show the importance of quercetin for its therapeutic potential in treatment of leukemias.
Citation Count: 54
Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest
(Taylor & Francis Ltd, 2013) Gokbulut, Aysun Adan; Apohan, Elif; Baran, Yusuf; Baran, Yusuf
Chronic lymphocytic leukemia (CLL), defined by accumulation of pathogenic B cells, has a very complex biology due to various factors such as inherited, host, and enviromental factors. Recently, finding new therapeutic agents or development of novel treatment strategies have been paid attention. Resveratrol and quercetin, important phytoalexins found in many plants, have been reported to have cytotoxic effects on various types of cancer. In this study, we examined cytotoxic, cytostatic, and apoptotic effects of these two important phenolic compounds on 232B4 human CLL cells. Cytotoxic effects of resveratrol and quercetin were determined by MTT cell proliferation assay. Changes in caspase-3 enzyme activity were measured using caspase-3 colorimetric assay. Annexin V-FITC/PI double staining was performed to measure apoptotic cell population. Effects of resveratrol and quercetin on cell cycle profiles of CLL cells were investigated by flow cytometry. Treatment of CLL cells with resveratrol and quercetin caused dose dependent inhibition of cell proliferation and increased apoptotic cell population through induction of caspase-3 activity. Cell cycle analysis displayed cell cycle arrest mainly in G0/G1 for both polyphenols. Our data, in total, showed for the first time that resveratrol and quercetin might block CLL growth through inducing apoptosis and cell cycle arrest.
Citation Count: 9
The roles of epigenetic modifications of proapoptotic BID and BIM genes in imatinib-resistant chronic myeloid leukemia cells
(Taylor & Francis Ltd, 2013) Bozkurt, Sureyya; Ozkan, Tulin; Ozmen, Fusun; Baran, Yusuf; Sunguroglu, Asuman; Kansu, Emin; Baran, Yusuf
In chronic myeloid leukemia (CML), epigenetic modifications such as promoter hypermethylation and inactive histone modification are known mechanisms of drug resistance. In our study, we investigated the roles of promoter hypermethylation of BIM and BID genes and H3K27me3 histone modification on imatinib resistance. We detected higher expression levels of BIM and BID genes and lower expression levels of EZH2, EED2, SIRT1, and SUZ12 genes in imatinib-resistant K562/IMA-3 cells compared to imatinib-non-resistant K562 cells. While we determined the EZH2 and DNMT enzymes as bounded to the promoter of the BIM gene, we did not detect hypermethylation of this promoter. We also found the H3K27me3 histone modification promoter of BIM and BID genes in both cell lines. In conclusion, our results support the notion that DNA promoter methylation may be formed independently from EZH2-H3K27me3 and pro-apoptotic BIM and BID genes are not methyllated in the imatinib resistance of CML cells.
Citation Count: 0
Spectral Test Generation for Boolean Expressions
(World Scientific Publ Co Pte Ltd, 2023) Ayav, Tolga; Ayav, Tolga; Bilgisayar Mühendisliği Bölümü
This paper presents a novel method for testing Boolean expressions. It is based on spectral, aka Fourier analysis of Boolean functions which is exploited to generate test inputs. The approach has three important contributions: (i) It generates a relatively small test suite with a high capability of fault detection, (ii) The test suite is prioritized such that expected fault detection time is shorter, (iii) It is entirely mathematical relying on a simple and straightforward formula. The proposed method is formulated and evaluations are performed on both synthetic and real expressions. It is also compared with two common test generation criteria, MC/DC and Minimal MUMCUT. Evaluations show that the test suite generated by the spectral approach is relatively small while expressing the capability of a better and quicker fault detection. The approach presented in this paper provides a useful insight into how spectral/Fourier analysis of Boolean functions can be exploited in software testing.
Citation Count: 0
Studying the Co-Evolution of Source Code and Acceptance Tests
(World Scientific Publ Co Pte Ltd, 2023) Yalcin, Ali Gorkem; Tuglular, Tugkan; Tuğlular, Tuğkan; Bilgisayar Mühendisliği Bölümü
Testing is a vital part of achieving good-quality software. Deploying untested code can cause system crashes and unexpected behavior. To reduce these problems, testing should evolve with coding. In addition, test suites should not remain static throughout the software versions. Since whenever software gets updated, new functionalities are added, or existing functionalities are changed, test suites should be updated along with the software. Software repositories contain valuable information about the software systems. Access to older versions and differentiating adjacent versions' source code and acceptance test changes can provide information about the evolution process of the software. This research proposes a method and implementation to analyze 21 open-source real-world projects hosted on GitHub regarding the co-evolution of both software and its acceptance test suites. Related projects are retrieved from repositories, their versions are analyzed, graphs are created, and analysis related to the co-evolution process is performed. Observations show that the source code is getting updated more frequently than the acceptance tests. They indicate a pattern that source code and acceptance tests do not evolve together. Moreover, the analysis showed that a few acceptance tests test most of the functionalities that take a significant line of code.
Citation Count: 0
Unifying Behavioral and Feature Modeling for Testing of Software Product Lines
(World Scientific Publ Co Pte Ltd, 2023) Belli, Fevzi; Tuglular, Tugkan; Ufuktepe, Ekincan; Tuğlular, Tuğkan; Bilgisayar Mühendisliği Bölümü
Existing software product line (SPL) engineering testing approaches generally provide positive testing that validates the SPL's functionality. Negative testing is commonly neglected. This research aims to unify behavioral and feature models of an SPL, enable testing before and after variability binding for domain-centric and product-centric testing, and combine positive and negative testing for a holistic testing view. This study suggests behavioral modeling with event sequence graphs (ESGs). This heterogeneous modeling strategy supports bottom-up domain testing and top-down product testing with the feature model. This new feature-oriented ESG test creation method generates shorter test sequences than the original ESG optimum test sequences. Statechart and original ESG test-generating methods are compared. Positive testing findings are similar. The Statechart technique generated 12 test cases with 59 events, whereas the ESG technique created six test cases with 60 events. The ESG technique generated 205 negative test cases with 858 events with the Test Suite Designer tool. However, the Conformiq Designer tool for the Statechart technique does not have a negative test case generation capability. It is shown that the proposed ESG-based holistic approach confirms not only the desirable (positive) properties but also the undesirable (negative) ones. As an additional research, the traditional ESG test-generating approach is compared to the new feature-oriented method on six SPLs of different sizes and features. Our case study results show that the traditional ESG test generation approach demonstrated higher positive test generation scores compare to the proposed feature-oriented test generation approach. However, our proposed feature-oriented test generation approach is capable of generating shorter test sequences, which could be beneficial for reducing the execution time of test cases compared to traditional ESG approach. Finally, our case study has also shown that regardless of the test generation approach, there has been found no significant difference between the Bottom-up and Top-down test strategies with respect to their positive test generation scores.

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