Research Outputs

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    PublicationOpen Access
    3D engineered neural co-culture model and neurovascular effects of marine fungi-derived citreohybridonol
    (American Institute of Physics (AIP) Publishing, 2022) Polat, İrem; Özkaya, Ferhat Can; El-Neketi, Mona; Ebrahim, Weaam; Şengül, Gülgün; Department of Mechanical Engineering; Sokullu, Emel; Sarabi, Misagh Rezapour; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); School of Medicine; Graduate School of Sciences and Engineering; College of Engineering; 163024; N/A; 291971
    Marine-based biomolecules are emerging metabolites that have gained attention for developing novel biomaterials, drugs, and pharmaceutical in vitro platforms. Here, we developed a 3D engineered neural co-culture model via a 3D prototyped sliding frame-platform for multi-step UV lithography and investigated the neurovascular potential of citreohybridonol in neuroblastoma treatment. Citreohybridonol was isolated from a sponge-derived fungus Penicillium atrovenetum. The model was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy analysis. Human umbilical cord vein endothelial cells (HUVECs) and neuroblastoma (SH-SY5Y) cell lines were encapsulated in gelatin methacrylate (GelMA) with and without citreohybridonol. The effect of citreohybridonol on the proliferation capacity of cells was assessed via cell viability and immunostaining assays. GelMA and 3D culture characterization indicated that the cells were successfully encapsulated as axenic and mixed with/without citreohybridonol. The cytotoxic test confirmed that the 3D microenvironment was non-toxic for cultural experiments, and it showed the inhibitory effects of citreohybridonol on SH-SY5Y cells and induced the proliferation of HUVECs. Finally, immunohistochemical staining demonstrated that citreohybridonol suppressed SH-SY5Y cells and induced vascularization of HUVECs in mixed 3D cell culture.
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    Publication
    Cell-specific and post-hoc spatial clustering tests based on nearest neighbor contingency tables
    (Korean Statistical Soc, 2017) Department of Mathematics; Ceyhan, Elvan; Faculty Member; Department of Mathematics; College of Sciences; N/A
    Spatial clustering patterns in a multi-class setting such as segregation and association between classes have important implications in various fields, e.g., in ecology, and can be tested using nearest neighbor contingency tables (NNCTs). a NNCT is constructed based on the types of the nearest neighbor (NN) pairs and their frequencies. We survey the cell-specific (or pairwise) and overall segregation tests based on NNCTs in literature and introduce new ones and determine their asymptotic distributions. We demonstrate that cell-specific tests enjoy asymptotic normality, while overall tests have chi-square distributions asymptotically. Some of the overall tests are confounded by the unstable generalized inverse of the rank-deficient covariance matrix. To overcome this problem, we propose rank-based corrections for the overall tests to stabilize their behavior. We also perform an extensive' Monte Carlo simulation study to compare the finite sample performance of the tests in terms of empirical size and power based on the asymptotic and Monte Carlo critical values and determine the tests that have the best size and power performance and are robust to differences in relative abundances (of the classes). in addition to the cell-specific tests, we discuss one(-class)-versus-rest type of tests as post-hoc,tests after a significant overall test. We also introduce the concepts of total, strong, and partial segregatioN/Association to differentiate different levels of these patterns. We compare the new tests with the existing NNCT-tests in literature with simulations and illustrate the tests on an ecological data set. (C) 2016 the Korean Statistical Society. Published by Elsevier B.V. all rights reserved.
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    Publication
    Line segmentation of individual demographic data from Arabic handwritten population registers of Ottoman Empire
    (Springer International Publishing Ag, 2021) N/A; Department of History; Can, Yekta Said; Kabadayı, Mustafa Erdem; Researcher; Faculty Member; Department of History; College of Social Sciences and Humanities; College of Social Sciences and Humanities; N/A; 33267
    Recently, more and more studies have applied state-of-the-art algorithms for extracting information from handwritten historical documents. Line segmentation is a vital stage in the HTR systems; it directly affects the character segmentation stage, which affects the recognition success. In this study, we first applied deep learning-based layout analysis techniques to detect individuals in the first Ottoman population register series collected between the 1840s and 1860s. Then, we used a star path planning algorithm-based line segmentation to the demographic information of these detected individuals in these registers. We achieved encouraging results from the selected regions, which could be used to recognize the text in these registers.
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    Noninvasive in vivo determination of residual strains and stresses
    (ASME, 2015) N/A; Department of Molecular Biology and Genetics; Department of Mechanical Engineering; Donmazov, Samir; Pişkin, Şenol; Pekkan, Kerem; PhD Student; Researcher; Faculty Member; Department of Molecular Biology and Genetics; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 148702; 161845
    Vascular growth and remodeling during embryonic development are associated with blood flow and pressure induced stress distribution, in which residual strains and stresses play a central role. Residual strains are typically measured by performing in vitro tests on the excised vascular tissue. In this paper, we investigated the possibility of estimating residual strains and stresses using physiological pressure-radius data obtained through in vivo noninvasive measurement techniques, such as optical coherence tomography or ultrasound modalities. This analytical approach first tested with in vitro results using experimental data sets for three different arteries such as rabbit carotid artery, rabbit thoracic artery, and human carotid artery based on Fung's pseudostrain energy function and Delfino's exponential strain energy function (SEF). We also examined residual strains and stresses in the human swine iliac artery using the in vivo experimental ultrasound data sets corresponding to the systolic-to-diastolic region only. This allowed computation of the in vivo residual stress information for loading and unloading states separately. Residual strain parameters as well as the material parameters were successfully computed with high accuracy, where the relative errors are introduced in the range of 0-7.5%. Corresponding residual stress distributions demonstrated global errors all in acceptable ranges. A slight discrepancy was observed in the computed reduced axial force. Results of computations performed based on in vivo experimental data obtained from loading and unloading states of the artery exhibited alterations in material properties and residual strain parameters as well. Emerging noninvasive measurement techniques combined with the present analytical approach can be used to estimate residual strains and stresses in vascular tissues as a precursor for growth estimates. This approach is also validated with a finite element model of a general two-layered artery, where the material remodeling states and residual strain generation are investigated.
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    PublicationOpen Access
    Optimal operation of a three-level quantum heat engine and universal nature of efficiency
    (Elsevier, 2020) Chawner, Samuel J. R. A.; Mihaljevic, Marina; Morrison, Sinead; Maillard, Anne M.; Nowakowska, Beata; van den Bree, Marianne B. M.; Swillen, Ann; Eser, Hale Yapıcı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 134359
    Background: several rare copy number variants have been identified to confer risk for neurodevelopmental disorders (NDD-CNVs), and increasingly NDD-CNVs are being identified in patients. There is a clinical need to understand the phenotypes of NDD- CNVs. However due to rarity of NDD-CNVs in the population, within individual countries there is a limited number of NDD-CNV carriers who can participate in research. The paneuropean MINDDS (Maximizing Impact of Research in Neurodevelopmental Disorders) consortium was established in part to address this issue. Methodology: a survey was developed to scope out the current landscape of NDD-CNV research across member countries of the MINDDS consortium, and to identify clinical cohorts with potential for future research. Results: 36 centres from across 16 countries completed the survey. We provide a list of centres who can be contacted for future collaborations. 3844 NDD-CNV carriers were identified across clinical and research centres spanning a range of medical specialties, including psychiatry, paediatrics, medical genetics. A broad range of phenotypic data was available; including medical history, developmental history, family history and anthropometric data. In 12/16 countries, over 75% of NDD-CNV carriers could be recontacted for future studies. Conclusion: this survey has highlighted the potential within Europe for large multi-centre studies of NDD-CNV carriers, to improve knowledge of the complex relationship between NDD-CNV and clinical phenotype. The MINNDS consortium is in a position to facilitate collaboration, data-sharing and knowledge exchange on NDD-CNV phenotypes across Europe.
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    PublicationOpen Access
    Patient-specific hemodynamics of new coronary artery bypass configurations
    (Springer, 2020) Pişkin, Senol; Tenekecioğlu, Erhan; Karagöz, Haldun; N/A; Department of Mechanical Engineering; Rezaeimoghaddam, Mohammad; Oğuz, Gökçe Nur; Lashkarinia, Seyedeh Samaneh; Pekkan, Kerem; Ateş, Mehmet Şanser; Bozkaya, Tijen Alkan; Researcher; Faculty Member; Doctor; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; Koç University Hospital; N/A; N/A; N/A; 161845; N/A; N/A
    Purpose: this study aims to quantify the patient-specific hemodynamics of complex conduit routing configurations of coronary artery bypass grafting (CABG) operation which are specifically suitable for off-pump surgeries. Coronary perfusion efficacy and local hemodynamics of multiple left internal mammary artery (LIMA) with sequential and end-to-side anastomosis are investigated. Using a full anatomical model comprised of aortic arch and coronary artery branches the optimum perfusion configuration in multi-vessel coronary artery stenosis is desired. Methodology: two clinically relevant CABG configurations are created using a virtual surgical planning tool where for each configuration set, the stenosis level, anastomosis distance and angle were varied. A non-Newtonian computational fluid dynamics solver in OpenFOAM incorporated with resistance boundary conditions representing the coronary perfusion physiology was developed. The numerical accuracy is verified and results agreed well with a validated commercial cardiovascular flow solver and experiments. For segmental performance analysis, new coronary perfusion indices to quantify deviation from the healthy scenario were introduced. Results: the first simulation configuration set;-a CABG targeting two stenos sites on the left anterior descending artery (LAD), the LIMA graft was capable of 31 mL/min blood supply for all the parametric cases and uphold the healthy LAD perfusion in agreement with the clinical experience. In the second end-to-side anastomosed graft configuration set;-the radial artery graft anastomosed to LIMA, a maximum of 64 mL/min flow rate in LIMA was observed. However, except LAD, the obtuse marginal (OM) and second marginal artery (m2) suffered poor perfusion. In the first set, average wall shear stress (WSS) were in the range of 4 to 35 dyns/cm(2)for in LAD. Nevertheless, for second configuration sets the WSS values were higher as the LIMA could not supply enough blood to OM and m2. Conclusion: the virtual surgical configurations have the potential to improve the quality of operation by providing quantitative surgical insight. The degree of stenosis is a critical factor in terms of coronary perfusion and WSS. The sequential anastomosis can be done safely if the anastomosis angle is less than 90 degrees regardless of degree of stenosis. The smaller proposed perfusion index value,O(0.04 - 0) x 10(2), enable us to quantify the post-op hemodynamic performance by comparing with the ideal healthy physiological flow.
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    PublicationOpen Access
    Privado: privacy-preserving group-based advertising using multiple independent social network providers
    (Association for Computing Machinery (ACM), 2020) Department of Computer Engineering; Boshrooyeh, Sanaz Taheri; Küpçü, Alptekin; Özkasap, Öznur; Faculty Member; Department of Computer Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 168060; 113507
    Online Social Networks (OSNs) offer free storage and social networking services through which users can communicate personal information with one another. The personal information of the users collected by the OSN provider comes with privacy problems when being monetized for advertising purposes. To protect user privacy, existing studies propose utilizing data encryption that immediately prevents OSNs from monetizing users data and hence leaves secure OSNs with no convincing commercial model. To address this problem, we propose Privado as a privacy-preserving group-based advertising mechanism to be integrated into se- cure OSNs to re-empower monetizing ability. Privado is run by N servers, each provided by an independent provider. User privacy is protected against an active malicious adversary controlling N - 1 providers, all the advertisers, and a large fraction of the users. We base our design on the group-based advertising notion to protect user privacy, which is not possible in the personalized variant. Our design also delivers advertising transparency; the procedure of identifying target customers is operated solely by the OSN servers without getting users and advertisers involved. We carry out experiments to examine the advertising running time under various number of servers and group sizes. We also argue about the optimum number of servers with respect to user privacy and advertising running time.
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    PublicationOpen Access
    Starting small to communicate
    (Elsevier, 2020) Kubilay, Elif; Department of Economics; Atakan, Alp Enver; Koçkesen, Levent; Faculty Member; Faculty Member; Department of Economics; College of Administrative Sciences and Economics; 39383; 37861
    We analyze a repeated cheap-talk game in which the receiver is privately informed about the conflict of interest between herself and the sender and either the sender or the receiver controls the stakes involved in their relationship. We focus on payoff-dominant equilibria that satisfy a Markovian property and show that if the potential conflict of interest is large, then the stakes increase over time, i.e., “starting small” is the unique equilibrium arrangement. In each period, the receiver plays the sender's ideal action with positive probability and the sender provides full information as long as he has always observed his ideal actions in the past. We also show that as the potential conflict of interest increases, the extent to which the stakes are back-loaded increases, i.e., stakes are initially smaller but grow faster.
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    PublicationOpen Access
    Turkish ectodermal dysplasia cohort: from phenotype to genotype in 17 families
    (Karger Publishers, 2019) Güven, Yeliz; Bal, Elodie; Altunoğlu, Umut; Hadj-Rabia, Smail; Koruyucu, Mine; Tuna, Elif Bahar; Çıldır, Şule; Aktören, Oya; Bodemer, Christine; Uyguner, Zehra Oya; Smahi, Asma; N/A; Börklü Yücel, Esra; Kayserili, Hülya; PhD Student; Faculty Member; School of Medicine; N/A; 7945
    Hypohidrotic or anhidrotic ectodermal dysplasia (HED/EDA) is characterized by impaired development of the hair, teeth, or sweat glands. HED/EDA is inherited in an X-linked, autosomal dominant, or autosomal recessive pattern and caused by the pathogenic variants in 4 genes: EDA, EDAR, EDARADD, and WNT10A. The aim of the present study was to perform molecular screening of these 4 genes in a cohort of Turkish individuals diagnosed with HED/EDA. We screened for pathogenic variants of WNT10A, EDA, EDAR, and EDARADD through Sanger sequencing. We further assessed the clinical profiles of the affected individuals in order to establish phenotype-genotype correlation. In 17 (63%) out of 27 families, 17 pathogenic variants, 8 being novel, were detected in the 4 well-known ectodermal dysplasia genes. EDAR and EDA variants were identified in 6 families each, WNT10A variants in 4, and an EDARADD variant in 1, accounting for 35.3, 35.3, 23.5, and 5.9% of mutation-positive families, respectively. The low mutation detection rate of the cohort and the number of the EDAR pathogenic variants being as high as the EDA ones were the most noteworthy findings which could be attributed to the high consanguinity rate.
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    PublicationOpen Access
    Verifiable dynamic searchable encryption
    (TÜBİTAK, 2019) Department of Computer Engineering; Etemad, Mohammad; Küpçü, Alptekin; PhD Student; Department of Computer Engineering; Graduate School of Sciences and Engineering; N/A; 168060
    Using regular encryption schemes to protect the privacy of the outsourced data implies that the client should sacrifice functionality for security. Searchable symmetric encryption (SSE) schemes encrypt the data in a way that the client can later search and selectively retrieve the required data. Many SSE schemes have been proposed, starting with static constructions, and then dynamic and adaptively secure constructions but usually in the honest-but-curious model. We propose a verifiable dynamic SSE scheme that is adaptively secure against malicious adversaries. Our scheme supports file modification, which is essential for efficiently working with large files, in addition to the ability to add/delete files. While our main construction is proven secure in the random oracle model (ROM), we also present a solution secure in the standard model with full security proof. Our experiments show that our scheme in the ROM performs a search within a few milliseconds, verifies the result in another few milliseconds, and has a proof overhead of 0.01% only. Our standard model solution, while being asymptotically slower, is still practical, requiring only a small client memory (e.g., ≃488 KB) even for a large file collection (e.g., ≃10 GB), and necessitates small tokens (e.g., ≃156 KB for search and ≃362 KB for file operations).