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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery(Elsevier, 2020) Ekinci, Duygu; N/A; Department of Chemical and Biological Engineering; Batool, Syeda Rubab; Nazeer, Muhammad Anwaar; Kızılel, Seda; Şahin, Afsun; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; 28376; 171267Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.Publication Open Access The structural basis of Akt PH domain interaction with calmodulin(Elsevier, 2021) Jang, Hyunbum; Nussinov, Ruth; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Weako, Jackson; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 26605; 8745Akt plays a key role in the Ras/PI3K/Akt/mTOR signaling pathway. In breast cancer, Akt translocation to the plasma membrane is enabled by the interaction of its pleckstrin homology domain (PHD) with calmodulin (CaM). At the membrane, the conformational change promoted by PIP3 releases CaM and facilitates Thr308 and Ser473 phosphorylation and activation. Here, using modeling and molecular dynamics simulations, we aim to figure out how CaM interacts with Akt's PHD at the atomic level. Our simulations show that CaM-PHD interaction is thermodynamically stable and involves a beta-strand rather than an alpha-helix, in agreement with NMR data, and that electrostatic and hydrophobic interactions are critical. The PHD interacts with CaM lobes; however, multiple modes are possible. IP4, the polar head of PIP3, weakens the CaM-PHD interaction, implicating the release mechanism at the plasma membrane. Recently, we unraveled the mechanism of PI3K alpha activation at the atomistic level and the structural basis for Ras role in the activation. Here, our atomistic structural data clarify the mechanism of how CaM interacts, delivers, and releases Akt-the next node in the Ras/PI3K pathway-at the plasma membrane.Publication Open Access Database for CO2 separation performances of MOFs based on computational materials screening(American Chemical Society (ACS), 2018) Eruçar, İlknur; Department of Chemical and Biological Engineering; Altıntaş, Çiğdem; Avcı, Gökay; Harman, Hilal Dağlar; Azar, Ayda Nemati Vesali; Velioğlu, Sadiye; Keskin, Seda; Researcher; Post Doctorate Student; Department of Chemical and Biological Engineering; College of Engineering; N/A; N/A; N/A; N/A; N/A; 40548Metal-organic frameworks (MOFs) are potential adsorbents for CO2 capture. Because thousands of MOFs exist, computational studies become very useful in identifying the top performing materials for target applications in a time-effective manner. In this study, molecular simulations were performed to screen the MOF database to identify the best materials for CO2 separation from flue gas (CO2/N-2) and landfill gas (CO2/CH4) under realistic operating conditions. We validated the accuracy of our computational approach by comparing the simulation results for the CO2 uptakes, CO2/N-2 and CO2/CH4 selectivities of various types of MOFs with the available experimental data. Binary CO2/N-2 and CO2/CH4 mixture adsorption data were then calculated for the entire MOF database. These data were then used to predict selectivity, working capacity, regenerability, and separation potential of MOFs. The top performing MOF adsorbents that can separate CO2/N-2 and CO2/CH4 with high performance were identified. Molecular simulations for the adsorption of a ternary CO2/N-2/CH4 mixture were performed for these top materials to provide a more realistic performance assessment of MOF adsorbents. The structure-performance analysis showed that MOFs with Delta Q(st)(0) > 30 kJ/mol, 3.8 angstrom < pore-limiting diameter < 5 angstrom, 5 angstrom < largest cavity diameter < 7.5 angstrom, 0.5 < phi < 0.75, surface area < 1000 m(2)/g, and rho > 1 g/cm(3) are the best candidates for selective separation of CO2 from flue gas and landfill gas. This information will be very useful to design novel MOFs exhibiting high CO2 separation potentials. Finally, an online, freely accessible database https://cosmoserc.ku.edu.tr was established, for the first time in the literature, which reports all of the computed adsorbent metrics of 3816 MOFs for CO2/N-2, CO2/CH4, and CO2/N-2/CH4 separations in addition to various structural properties of MOFs.Publication Open Access Preparation of Pt/Al2O3 and PtPd/Al2O3 catalysts by supercritical deposition and their performance for oxidation of nitric oxide and propene(Elsevier, 2020) Şanlı Yıldız, D.; Özener, B.; Hisar, G.; Rommel, S.; Aindow, M.; Department of Chemical and Biological Engineering; Güneş, Hande; Bozbağ, Selmi Erim; Erkey, Can; Researcher; Faculty Member; Department of Chemical and Biological Engineering; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 29633Pt/Al2O3 and bimetallic PtPd/Al2O3 catalysts were prepared via supercritical deposition method using supercritical carbon dioxide. The effects of Pt loading of Pt/Al2O3 and Pd addition to Pt/Al2O3 on particle size, particle size distribution (PSD) and activity for NO and C3H6 oxidation and C3H6-selective catalytic reduction (C3H6-SCR) were investigated. Pt/Al2O3 catalysts were prepared with Pt loadings of 0.6, 1.2 and 2.1 wt% and a bimetallic PtPd/Al2O3 catalyst was prepared with total metal loading of 1.4 wt% and Pt:Pd molar ratio of 1.3:1. A small fraction of the particles agglomerated after calcination at 550 °C. Around 98 % of the particles had an average particle size of ?1 nm. The rest of the particles were larger and average size of these larger particles was ?10 nm for monometallic catalysts and ?6.5 nm for PtPd/Al2O3. All catalysts were found to be active for NO and C3H6 oxidation and C3H6-SCR reactions. NO oxidation performance of 1.2 wt% Pt/Al2O3 catalyst was the highest. C3H6 oxidation activity increased with increasing metal content. Light-off temperature for C3H6 oxidation shifted to higher temperature in the presence of NO, suggesting competitive oxidation of C3H6 and NO. Concentration profiles indicated that C3H6-SCR started when C3H6 conversion by oxidation reached 50 %; C3H6 was consumed both by oxidation and C3H6-SCR at higher conversions.Publication Open Access Improving CO2 separation performance of MIL-53(Al) by incorporating 1-N-Butyl-3-methylimidazolium methyl sulfate(Wiley, 2019) Department of Chemical and Biological Engineering; N/A; Kulak, Harun; Polat, Hüsamettin Mert; Kavak, Safiyye; Keskin, Seda; Uzun, Alper; Faculty Member; Department of Chemical and Biological Engineering; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; N/A; N/A; N/A; 40548; 599171-n-Butyl-3-methylimidazolium methyl sulfate is incorporated into MIL-53(Al). Detailed characterization is done by X-ray fluorescence, Brunauer-Emmett-Teller surface area, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Results show that ionic liquid (IL) interacts directly with the framework, significantly modifying the electronic environment of MIL-53(Al). Based on the volumetric gas adsorption measurements, CO2, CH4, and N-2 adsorption capacities decreased from 112.0, 46.4, and 19.6 cc (STP) g(MIL-53(Al))(-1) to 42.2, 13.0, and 4.3 cc (STP) g(MIL-53(Al))(-1) at 5 bar, respectively, upon IL incorporation. Data show that this postsynthesis modification leads to more than two and threefold increase in the ideal selectivity for CO2 over CH4 and N-2 separations, respectively, as compared with pristine MIL-53(Al). The isosteric heat of adsorption (Qst) values show that IL incorporation increases CO2 affinity and decreases CH4 and N-2 affinities. Cycling adsorption-desorption measurements show that the composite could be regenerated with almost no decrease in the CO2 adsorption capacity for six cycles and confirm the lack of any significant IL leaching. The results offer MIL-53(Al) as an excellent platform for the development of a new class of IL/MOF composites with exceptional performance for CO2 separation.Publication Open Access SimMBM channel simulator for media-based modulation systems(Institute of Electrical and Electronics Engineers (IEEE), 2021) Yiğit Zehra; Altunbaş, İbrahim; Department of Chemical and Biological Engineering; Başar, Ertuğrul; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 149116Media-based modulation (MBM), exploiting rich scattering properties of transmission environments via different radiation patterns of a single reconfigurable antenna (RA), has brought new insights into future communication systems. In this study, considering this innovative transmission principle, we introduce the realistic, two-dimensional (2D), and open-source SimMBM channel simulator to support various applications of MBM systems at sub-6 GHz frequency band in different environments.Publication Open Access Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells(Elsevier, 2019) N/A; Department of Chemical and Biological Engineering; Oran, Dilem Ceren; Lokumcu, Tolga; Bal, Tuğba; İnceoğlu, Yasemin; Albayrak, Özgür; Erkan, Murat Mert; Kurtoğlu, Metin; Can, Füsun; Önder, Tuğba Bağcı; Kızılel, Seda; Akolpoğlu, Mükrime Birgül; Faculty Member; Faculty Member; Master Student; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; Graduate School of Health Sciences; College of Engineering; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 103165; 184359; 28376; N/AType 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.Publication Open Access Hypothetical yet effective: computational identification of high-performing MOFs for CO2 capture(Elsevier, 2022) Department of Chemical and Biological Engineering; Demir, Hakan; Keskin, Seda; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; N/A; 40548With the advances in computational resources and algorithms, computer simulations are being increasingly used to tackle the most challenging problems of the world. Among them, CO2 capture is a topic that needs imminent attention as the presence of high levels of CO2 in the air can lead to drastic shifts in global climate. Here, a recently developed hypothetical metal-organic framework (MOF) database comprised of anion-pillared (AP) MOFs is computationally screened for the separation of CO2/CO, CO2/H-2, and CO2/N-2 gas mixtures at room temperature. The best performing MOFs are identified using three performance metrics, adsorption selectivity, working capacity, and regenerability, in conjunction. In these top materials, the preferential adsorption sites are illustrated, which will be useful in guiding the experimental design of new MOFs with extraordinarily high CO2 selectivities. The favorable separation performances of AP MOFs suggest that efficient gas separations can be conducted using MOFs without open metal sites.Publication Open Access The epidemiological and molecular characterization of vancomycin-resistant enterococci Isolated from rectal swab samples of hospitalized patients in Turkey(Clinical Laboratory, 2014) Çakırlar, Fatma Köksal; Karakullukçu, Asiye; Sirekbasan, Serhat; Bağdatlı, Yaşar; Department of Chemical and Biological Engineering; Barış, İbrahim; Kavaklı, İbrahim Halil; Teaching Faculty; Department of Chemical and Biological Engineering; College of Engineering; 111629; 40319Background: Vancomycin-resistant enterococci (VRE) are a serious problem all over the world. The present study was conducted to investigate antimicrobial resistance patterns, genotypes, clonal relationship, and virulence factors of VRE species isolated from rectal swab samples of hospitalized patients, patient's relatives, and medical staff at Istanbul University Cerrahpasa Medical School hospital. Methods: The VRE isolates were typed with an automated VITEK system and their antibiotic sensibilities were analysed by disc diffusion and Etest (R) method. The molecular characterization and clonal relationships were performed using a PCR method and virulence genes by sequence typing. Results: A total of 100 (10.3%) of the 971 patients were colonized with VRE. None of the investigated 25 patient's relatives and 45 medical staff carried VRE. All VRE strains were identified as E. faecium. They were vanA geno-type and originated from a single clone. VRE strains exhibited multi-drug resistance. High-level gentamicin-resistance was 93%. However, lower resistance rates were found for linezolid (40%) and quinopristin-dalfopristin (11%). The enterococcal surface protein gene esp was found positive in 87 of 100 isolates, and four strains were positive for the cylB (cytolysin) gene. Conclusions: The identification of VRE strains to the species level and detection of virulence genes will assist in infection control practices.Publication Open Access Synchronous and asynchronous response in dynamically perturbed proteins(American Chemical Society (ACS), 2021) Erkip, Albert; Erman, Batu; Department of Chemical and Biological Engineering; Hacısüleyman, Aysima; Erman, Burak; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 179997We present a dynamic perturbation-response model of proteins based on the Gaussian Network Model, where a residue is perturbed periodically, and the dynamic response of other residues is determined. The model shows that periodic perturbation causes a synchronous response in phase with the perturbation and an asynchronous response that is out of phase. The asynchronous component results from the viscous effects of the solvent and other dispersive factors in the system. The model is based on the solution of the Langevin equation in the presence of solvent, noise, and perturbation. We introduce several novel ideas: The concept of storage and loss compliance of the protein and their dependence on structure and frequency; the amount of work lost and the residues that contribute significantly to the lost work; new dynamic correlations that result from perturbation; causality, that is, the response of j when i is perturbed is not equal to the response of i when j is perturbed. As examples, we study two systems, namely, bovine rhodopsin and the class of nanobodies. The general results obtained are (i) synchronous and asynchronous correlations depend strongly on the frequency of perturbation, their magnitude decreases with increasing frequency, (ii) time-delayed mean-squared fluctuations of residues have only synchronous components. Asynchronicity is present only in cross correlations, that is, correlations between different residues, (iii) perturbation of loop residues leads to a large dissipation of work, (iv) correlations satisfy the hypothesis of pre-existing pathways according to which information transfer by perturbation rides on already existing equilibrium correlations in the system, (v) dynamic perturbation can introduce a selective response in the system, where the perturbation of each residue excites different sets of responding residues, and (vi) it is possible to identify nondissipative residues whose perturbation does not lead to dissipation in the protein. Despite its simplicity, the model explains several features of allosteric manipulation.