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Item Metadata only A facile method for cross-linking of methacrylated wood fibers for engineered wood composites(Elsevier, 2023) 0000-0001-6539-7748; 0000-0003-2593-1146; 0000-0002-9161-0765; 0000-0002-5329-1572; N/A; Bengu, Basak; Bicer, Aziz; Yarici, Tuga; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; N/A; N/A; N/A; Erkey, Can; Şenses, Erkan; Karaz, Selcan; Turhan, Emine Ayşe; Sarıoğlu, Ebru; Faculty Member; Faculty Member; Master Student; PhD Student; PhD Student; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Boron and Advanced Materials Application and Research Center (KUBAM) / Koç Üniversitesi Bor ve İleri Malzemeler Uygulama ve Araştırma Merkezi (KUBAM); College of Engineering; College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 29633; 280298; N/A; N/A; N/AChemical modifications are widely used to enhance the properties of wood composites and create a strong bonding mechanism for enhancing the dimensional stability, water resistance as well as decreasing carcinogenic formaldehyde emission. Esterification is the most-known modification way to enhance the durability of wood composites, but it does not improve mechanical performance. In this work, we demonstrated a two-step, easy and quick wood surface modification strategy based on microwave heating and UV crosslinking. Firstly, the fiber surface was reacted with methacrylic anhydride, then using methacrylated groups on wood, the fibers are covalently linked. As a proof-of-concept the fibers cross-linked within five minutes under UV radiation using benzophenone solution. Then, the effect of crosslinked wood fiber on the properties of mechanical and swelling of fiberboard were studied. Using SEM, FTIR-ATR, and swelling tests, we investigated the wood-based products' reaction mechanism, morphology, and internal bonding strength. The chemical cross-linking gives stronger bonding, compared to hydrogen bonding, between fibers even in wet conditions, resulting in a cross-linked foamlike structure. Also, wood panels were fabricated, compared to unmodified fibers, the internal bond strength and dimensional stability of fiberboards increased slightly. Overall, these results show that chemical cross-linking of wood fibers can be a fast and promising way to produce multi-functional wood composites.Item Metadata only Tetra-functional multilayer coatings for cardiovascular stent materials(Elsevier, 2023) 0000-0001-6624-3505; 0000-0002-6976-942X; 0000-0001-6753-9316; 0000-0001-5547-6653; 0000-0002-7698-0872; N/A; 0000-0002-4588-5231; 0000-0003-0984-0375; N/A; Department of Chemical and Biological Engineering; Department of Chemistry; N/A; N/A; N/A; Department of Molecular Biology and Genetics; N/A; N/A; N/A; Kavaklı, İbrahim Halil; Güner, Pınar Tatar; Motallebzadeh, Amir; Yalçın, Özlem; Gürpınar, Yunus; Sürme, Saliha; Ijaz, Aatif; Saadatlou, Ghazaleh Azizi; Sipahioğlu, Dilara; Faculty Member; Teaching Faculty; Researcher; Faculty Member; Researcher; Teaching Faculty; Researcher; PhD Student; Master Student; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; College of Sciences; N/A; School of Medicine; N/A; College of Sciences; N/A; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 40319; 188227; N/A; 218440; N/A; 389349; N/A; N/A; N/AFunctional coatings have been of great interest in enhancing the performance of implants in recent years. Here, for the first time, preparation and characterization of a tetra-functional coating is reported, exhibiting anticorrosion, antibacterial, biocompatible, and anticoagulant behaviors. Poly(2-ethyl-2-oxazoline)-copolyethyleneimine (PEOX-co-PEI) stabilized silver nanoparticles (AgNPs) and heparin were used to prepare the multifunctional multilayers. The coatings were deposited on nitinol and 316 L stainless steel substrates, the most used materials in coronary stents, via layer-by-layer (LbL) technique. Corrosion current density values obtained from Tafel plots are 1.61 x 10-9 A/cm2 and 6.79 x 10-8A/cm2 for coated and uncoated 316 L substrate, respectively. Similarly, the corrosion current density values shifted from 1.00 x 10-8A/cm2 for uncoated nitinol to 4.77 x 10-10A/cm2 after coating. Contact killing method against gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa) bacterial species concluded that the presence of the coating on the surfaces of the materials reduces the number of the survived colonies (in CFU/mL) for more than 99.9%independent of the underlying metal within 3 hours of incubation time. Prepared coatings demonstrated above 90% relative viability compared to the positive control in MTT assay using human umbilical vein endothelial cells (HUVEC), indicating no cytotoxic effect on adjacent healthy cells. The coagulation assay also exhibited a 50% reduction in the coagulation rate after coating compared to the bare substrates, confirming the antithrombogenicity of the coatings.Item Metadata only The effect of synthesis conditions and process parameters on aerogel properties(Frontiers Media Sa, 2023) 0000-0001-6539-7748; 0000-0003-4471-2301; 0000-0001-6443-5669; 0000-0002-7380-5550; Payanda Konuk, Ozge; Alsuhile, Ala A. A. M.; Yousefzadeh, Hamed; Ulker, Zeynep; Bozbag, Selmi E.; Garcia-Gonzalez, C. A.; Smirnova, I.; Erkey, Can; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; N/A; N/A; Erkey, Can; Bozbağ, Selmi Erim; Konuk, Özge Payanda; Alsuhile, Ala Abdulalem Abdo Moqbel; Faculty Member; Researcher; PhD Student; PhD Student; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); College of Engineering; College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 29633; N/A; N/A; N/AAerogels are remarkable nanoporous materials with unique properties such as low density, high porosity, high specific surface area, and interconnected pore networks. In addition, their ability to be synthesized from various precursors such as inorganics, organics, or hybrid, and the tunability of their properties make them very attractive for many applications such as adsorption, thermal insulation, catalysts, tissue engineering, and drug delivery. The physical and chemical properties and pore structure of aerogels are crucial in determining their application areas. Moreover, it is possible to tailor the aerogel properties to meet the specific requirements of each application. This review presents a comprehensive review of synthesis conditions and process parameters in tailoring aerogel properties. The effective parameters from the dissolution of the precursor step to the supercritical drying step, including the carbonization process for carbon aerogels, are investigated from the studies reported in the literature.Item Metadata only Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2(American Society for Biochemistry and Molecular Biology Inc., 2023) 0000-0001-6624-3505; 0000-0003-2185-3259; 0000-0002-2817-1069; Gul, Seref; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; N/A; Kavaklı, İbrahim Halil; Barış, İbrahim; Parlak, Gizem Çağla; Faculty Member; Teaching Faculty; Master Student; College of Engineering; College of Sciences; Graduate School of Sciences and Engineering; 40319; 111629; N/ACryptochromes (CRYs) are essential components of the circadian clock, playing a pivotal role as transcriptional repressors. Despite their significance, the precise mechanisms underlying CRYs’ involvement in the circadian clock remain incompletely understood. In this study, we identified a rare CRY2 variant, p.Ser420Phe, from the 1000 Genomes Project and Ensembl database that is located in the functionally important coiled-coil-like helix (CC−helix) region. Functional characterization of this variant at the cellular level revealed that p.Ser420Phe CRY2 had reduced repression activity on CLOCK:BMAL1−driven transcription due to its reduced affinity to the core clock protein PER2 and defective translocation into the nucleus. Intriguingly, the CRY2 variant exhibited an unexpected resistance to degradation via the canonical proteasomal pathway, primarily due to the loss of interactions with E3 ligases (FBXL3 and FBXL21), which suggests Ser-420 of CRY2 is required for the interaction with E3 ligases. Further studies revealed that wild-type and CRY2 variants are degraded by the lysosomal-mediated degradation pathway, a mechanism not previously associated with CRY2. Surprisingly, our complementation study with Cry1−/−Cry2−/− double knockout mouse embryonic fibroblast cells indicated that the CRY2 variant caused a 7 h shorter circadian period length in contrast to the observed prolonged period length in CRY2−/− cell lines. In summary, this study reveals a hitherto unknown degradation pathway for CRY2, shedding new light on the regulation of circadian rhythm period length. © 2023 The AuthorsItem Metadata only Epigenetic-focused CRISPR/Cas9 screen identifies (absent, small, or homeotic)2-like protein (ASH2L) as a regulator of glioblastoma cell survival(Biomed Central Ltd, 2023) 0000-0003-3646-2613; 0000-0002-2372-9158; 0000-0001-7399-5844; 0000-0002-8936-3267; 0000-0002-2483-075X; 0000-0002-0389-9459; 0000-0001-6981-6962; 0000-0002-6544-9752; N/A; 0000-0002-8963-096X; 0000-0002-1111-7752; 0000-0001-7267-3632; 0000-0002-6525-3602; 0000-0002-0827-1767; 0000-0003-0202-8165; Nizamuddin, Sheikh; Biniossek, Martin; Kung, Sonia H. Y.; hilpott, Martin; Cribbs, Adam P.Timmers, H. T. Marc; N/A; N/A; N/A; N/A; Department of Industrial Engineering; Department of Chemical and Biological Engineering; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Önder, Tuğba Bağcı; Önder, Tamer Tevfik; Lack, Nathan Alan; Ayhan, Ceyda Açılan; Gönen, Mehmet; Tunçbağ, Nurcan; Syed, Hamzah; Aztekin, Can; Morova, Tunç; Şeker-Polat, Fidan; Cingöz, Ahmet; Bulut, İpek; Aksu, Ali Cenk; Kala, Ezgi Yağmur; Özyerli, Ezgi; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Master Student; Master Student; PhD Student; Researcher; PhD Student; PhD Student; PhD Student; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; School of Medicine; School of Medicine; College of Engineering; College of Engineering; School of Medicine; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; 184359; 42946; 120842; 219658; 237468; 245513; 318138; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/ABackground: Glioblastoma is the most common and aggressive primary brain tumor with extremely poor prognosis, highlighting an urgent need for developing novel treatment options. Identifying epigenetic vulnerabilities of cancer cells can provide excellent therapeutic intervention points for various types of cancers. Method: In this study, we investigated epigenetic regulators of glioblastoma cell survival through CRISPR/Cas9 based genetic ablation screens using a customized sgRNA library EpiDoKOL, which targets critical functional domains of chromatin modifiers. Results: Screens conducted in multiple cell lines revealed ASH2L, a histone lysine methyltransferase complex subunit, as a major regulator of glioblastoma cell viability. ASH2L depletion led to cell cycle arrest and apoptosis. RNA sequencing and greenCUT&RUN together identified a set of cell cycle regulatory genes, such as TRA2B, BARD1, KIF20B, ARID4A and SMARCC1 that were downregulated upon ASH2L depletion. Mass spectrometry analysis revealed the interaction partners of ASH2L in glioblastoma cell lines as SET1/MLL family members including SETD1A, SETD1B, MLL1 and MLL2. We further showed that glioblastoma cells had a differential dependency on expression of SET1/MLL family members for survival. The growth of ASH2L-depleted glioblastoma cells was markedly slower than controls in orthotopic in vivo models. TCGA analysis showed high ASH2L expression in glioblastoma compared to low grade gliomas and immunohistochemical analysis revealed significant ASH2L expression in glioblastoma tissues, attesting to its clinical relevance. Therefore, high throughput, robust and affordable screens with focused libraries, such as EpiDoKOL, holds great promise to enable rapid discovery of novel epigenetic regulators of cancer cell survival, such as ASH2L. Conclusion: Together, we suggest that targeting ASH2L could serve as a new therapeutic opportunity for glioblastoma. [MediaObject not available: see fulltext.] © 2023, The Author(s).Item Metadata only Development and characterization of decellularized lung extracellular matrix hydrogels(Journal of Visualized Experiments, 2023) 0000-0001-9092-2698; 0000-0001-8635-0279; 0000-0003-3004-7742; N/A; N/A; N/A; 0000-0003-1085-7625; N/A; N/A; Department of Chemical and Biological Engineering; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Kızılel, Seda; Öztürk, Ece; Karaoğlu, İsmail Can; Dansık, Aslı; Kuşoğlu, Alican; Yangın, Kardelen; Özkan, Sena Nur; Sarıca, Sevgi; Özdinç, Şevval; Faculty Member; Faculty Member; PhD Student; Master Student; PhD Student; PhD Student; PhD Student; PhD Student; Researcher; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; School of Medicine; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; Graduate School of Health Sciences; N/A; 28376; 326940; N/A; N/A; N/A; N/A; N/A; N/A; N/AThe use of extracellular matrix (ECM)-derived hydrogels in tissue engineering has become increasingly popular, as they can mimic cells' natural environment in vitro. However, maintaining the native biochemical content of the ECM, achieving mechanical stability, and comprehending the impact of the decellularization process on the mechanical properties of the ECM hydrogels are challenging. Here, a pipeline for decellularization of bovine lung tissue using two different protocols, downstream characterization of the effectiveness of decellularization, fabrication of reconstituted decellularized lung ECM hydrogels and assessment of their mechanical and cytocompatibility properties were described. Decellularization of the bovine lung was pursued using a physical (freeze-thaw cycles) or chemical (detergent-based) method. Hematoxylin and Eosin staining was performed to validate the decellularization and retention of major ECM components. For the evaluation of residual collagen and sulfated glycosaminoglycan (sGAG) content within the decellularized samples, Sirius red and Alcian blue staining techniques were employed, respectively. Mechanical properties of the decellularized lung ECM hydrogels were characterized by oscillatory rheology. The results suggest that decellularized bovine lung hydrogels can provide a reliable organotypic alternative to commercial ECM products by retaining most native ECM components. Furthermore, these findings reveal that the decellularization method of choice significantly affects gelation kinetics as well as the stiffness and viscoelastic properties of resulting hydrogels. © 2023 JoVE Journal of Visualized Experiments.Item Metadata only Dynamic regulation of the serine loop by distant mutations reveals allostery in cryptochrome1(Taylor and Francis Inc, 2023) 0000-0001-6624-3505; N/A; Gul, Seref; Department of Chemical and Biological Engineering; N/A; Kavaklı, İbrahim Halil; Özcan, Onur; Faculty Member; PhD Student; College of Engineering; Graduate School of Sciences and Engineering; 40319; N/ACryptochromes (CRYs) are essential components of the molecular clock that generates circadian rhythm. They inhibit BMAL1/CLOCK-driven transcription at the molecular level. There are two CRYs that have differential functions in the circadian clock in mammals. It is not precisely known how they achieve such differential functions. In this study, we performed molecular dynamic simulations on eight CRY mutants that have been experimentally shown to exhibit reduced repressor activities. Our results revealed that mutations in CRY1 affect the dynamic behavior of the serine loop and the availability of the secondary pocket, but not in CRY2. Further analysis of these CRY1 mutants indicated that the differential flexibility of the serine loop leads to changes in the volume of the secondary pocket. We also investigated the weak interactions between the amino acids in the serine loop and those in close proximity. Our findings highlighted the crucial roles of S44 and S45 in the dynamic behavior of the serine loop, specifically through their interactions with E382 in CRY1. Considering the clinical implications of altered CRY1 function, our study opens up new possibilities for the development of drugs that target the allosteric regulation of CRY1.Communicated by Ramaswamy H. SarmaItem Metadata only Structural coverage of the human interactome(Oxford University Press, 2023) 0000-0002-2297-2113; 0000-0002-4202-4049; 0000-0002-0389-9459; 0000-0002-0349-4312; 0009-0000-4377-8865; Department of Computer Engineering; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; N/A; N/A; Gürsoy, Attila; Keskin, Özlem; Tunçbağ, Nurcan; Kösoğlu, Kayra; Aydın, Zeynep; Faculty Member; Faculty Member; Faculty Member; PhD Student; PhD Student; College of Engineering; College of Engineering; College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 8745; 26605; 245513; N/A; N/AComplex biological processes in cells are embedded in the interactome, representing the complete set of protein–protein interactions. Mapping and analyzing the protein structures are essential to fully comprehending these processes’ molecular details. Therefore, knowing the structural coverage of the interactome is important to show the current limitations. Structural modeling of protein–protein interactions requires accurate protein structures. In this study, we mapped all experimental structures to the reference human proteome. Later, we found the enrichment in structural coverage when complementary methods such as homology modeling and deep learning (AlphaFold) were included. We then collected the interactions from the literature and databases to form the reference human interactome, resulting in 117 897 non-redundant interactions. When we analyzed the structural coverage of the interactome, we found that the number of experimentally determined protein complex structures is scarce, corresponding to 3.95% of all binary interactions. We also analyzed known and modeled structures to potentially construct the structural interactome with a docking method. Our analysis showed that 12.97% of the interactions from HuRI and 73.62% and 32.94% from the filtered versions of STRING and HIPPIE could potentially be modeled with high structural coverage or accuracy, respectively. Overall, this paper provides an overview of the current state of structural coverage of the human proteome and interactome. © 2024 Oxford University Press. All rights reserved.Item Metadata only Physics informed piecewise linear neural networks for process optimization(Pergamon-Elsevier Science Ltd, 2023) 0000-0002-8498-4830; 0000-0001-8593-3341; Department of Chemical and Biological Engineering; N/A; Aydın, Erdal; Köksal, Ece Serenat; Faculty Member; PhD Student; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); College of Engineering; Graduate School of Sciences and Engineering; 311745; N/AConstructing first-principles models is usually a challenging and time-consuming task due to the complexity of real-life processes. On the other hand, data-driven modeling, particularly a neural network model, often suffers from overfitting and lack of useful and high-quality data. At the same time, embedding trained machine learning models directly into the optimization problems has become an effective and state-of-the-art approach for sur-rogate optimization, whose performance can be improved by physics-informed machine learning. This study proposes using piecewise linear neural network models with physics-informed knowledge for optimization problems with neural network models embedded. In addition to using widely accepted and naturally piecewise linear rectified linear unit (ReLU) activation functions, this study also suggests piecewise linear approximations for the hyperbolic tangent activation function to widen the domain. Optimization of three case studies, a blending process, an industrial distillation column, and a crude oil column are investigated. Physics-informed trained neural network-based optimal results are closer to global optimality for all cases. Finally, associated CPU times for the optimization problems are much shorter than the standard optimization results.Item Metadata only A novel smart disinfection system using 3D-printed and electrically conductive composite hydrogel(Springernature, 2024) 0000-0002-8316-9623; 0000-0001-6624-3505; N/A; 0000-0002-3511-3887; 0000-0003-1600-7322; Gul, Seref; Department of Mechanical Engineering; Department of Chemical and Biological Engineering; N/A; N/A; N/A; Lazoğlu, İsmail; Kavaklı, İbrahim Halil; Velioğlu, Başak; Malik, Anjum Naeem; Khan, Shaheryar Atta; Faculty Member; Faculty Member; Researcher; PhD Student; PhD Student; Manufacturing and Automation Research Center (MARC); College of Engineering; College of Engineering; N/A; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 179391; 40319; N/A; N/A; N/ASmart materials are ushering in the era of smart and adaptable products. Hydrogels are a distinct class of smart materials that can be 3D-printed to produce smart and active structures that can be used as sensors and actuators. The development and characterization of a 3D-printable and electrically conductive composite hydrogel, as well as its application in the development of a smart disinfection system, are discussed in this article. The developed composite hydrogel has a maximum electrical conductivity of 145 S.m-1, is stable up to 200 degrees C, and has a 3D printable rheology. Virtuous of its electrical conductivity, the composite hydrogel was used to create a smart disinfection system. Various disinfection systems have been adopted for the disinfection of contaminated surfaces; however, most of these systems require human evacuation from the surroundings due to the hazardous nature of the virucide. The proposed system is designed to disinfect contaminated surfaces on common-use equipment and is capable of real-time activation through user interaction. It employs a thermal disinfection process at 60 degrees C for 5 min and becomes ready for the next user once its temperature drops below 55 degrees C. This system consumes 1.64 Wh of energy per disinfection cycle and is suitable for scenarios with fewer than 60 user interactions in an 8-h work shift.