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Publication Metadata only A computational biomechanical investigation of posterior dynamic instrumentation: combination of dynamic rod and hinged (dynamic) screw(Asme, 2014) Kiapour, Ali; Goel, Vijay K.; N/A; N/A; Erbulut, Deniz Ufuk; Öktenoğlu, Bekir Tunç; Özer, Ali Fahir; Researcher; Faculty Member; School of Medicine, College of Engineering; School of Medicine; 37661; 220898; 1022Currently, rigid fixation systems are the gold standard for degenerative disk disease treatment. Dynamic fixation systems have been proposed as alternatives for the treatment of a variety of spinal disorders. These systems address the main drawbacks of traditional rigid fixation systems, such as adjacent segment degeneration and instrumentation failure. Pedicle-screw-based dynamic stabilization (PDS) is one type of these alternative systems. The aim of this study was to simulate the biomechanical effect of a novel posterior dynamic stabilization system, which is comprised of dynamic (hinged) screws interconnected with a coiled, spring-based dynamic rod (DSDR), and compare it to semirigid (DSRR and RSRR) and rigid stabilization (RSRR) systems. A validated finite element (FE) model of L1-S1 was used to quantify the biomechanical parameters of the spine, such as range of motion, intradiskal pressure, stresses and facet loads after single-level instrumentation with different posterior stabilization systems. The results obtained from in vitro experimental intact and instrumented spines were used to validate the FE model, and the validated model was then used to compare the biomechanical effects of different fixation and stabilization constructs with intact under a hybrid loading protocol. The segmental motion at L4-L5 increased by 9.5% and 16.3% in flexion and left rotation, respectively, in DSDR with respect to the intact spine, whereas it was reduced by 6.4% and 10.9% in extension and left-bending loads, respectively. After instrumentation-induced intradiskal pressure at adjacent segments, L3-L4 and L5-S1 became less than the intact in dynamic rod constructs (DSDR and RSDR) except in the RSDR model in extension where the motion was higher than intact by 9.7% at L3-L4 and 11.3% at L5-S1. The facet loads were insignificant, not exceeding 12N in any of the instrumented cases in flexion. In extension, the facet load in DSDR case was similar to that in intact spine. The dynamic rod constructions (DSDR and RSDR) led to a lesser peak stress at screws compared with rigid rod constructions (DSRR and RSRR) in all loading cases. A dynamic construct consisting of a dynamic rod and a dynamic screw did protect the adjacent level from excessive motion.Publication Metadata only A structural view of negative regulation of the toll-like receptor-mediated inflammatory pathway(Cell Press, 2015) Gursoy, Attila; Nussinov, Ruth; N/A; Department of Chemical and Biological Engineering; Maiorov, Emine Güven; Keskin, Özlem; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; The Center for Computational Biology and Bioinformatics (CCBB); Graduate School of Sciences and Engineering; College of Engineering; N/A; 26605Even though the Toll-like receptor (TLR) pathway is integral to inflammatory defense mechanisms, its excessive signaling may be devastating. Cells have acquired a cascade of strategies to regulate TLR signaling by targeting protein-protein interactions, or ubiquitin chains, but the details of the inhibition mechanisms are still unclear. Here, we provide the structural basis for the regulation of TLR signaling by constructing architectures of protein-protein interactions. Structural data suggest that 1) Toll/IL-1R (TIR) domain-containing regulators (BCAP, SIGIRR, and ST2) interfere with TIR domain signalosome formation; 2) major deubiquitinases such as A20, CYLD, and DUBA prevent association of TRAF6 and TRAF3 with their partners, in addition to removing K63-linked ubiquitin chains that serve as a docking platform for downstream effectors; 3) alternative downstream pathways of TLRs also restrict signaling by competing to bind common partners through shared binding sites. We also performed in silico mutagenesis analysis to characterize the effects of oncogenic mutations on the negative regulators and to observe the cellular outcome (whether there is/is not inflammation). Missense mutations that fall on interfaces and nonsense/frameshift mutations that result in truncated negative regulators disrupt the interactions with the targets, thereby enabling constitutive activation of the nuclear factor-kappa B, and contributing to chronic inflammation, autoimmune diseases, and oncogenesis.Publication Metadata only An all-aqueous approach for physical immobilization of PEG-lipid microgels on organoid surfaces(Elsevier, 2020) N/A; N/A; Department of Chemical and Biological Engineering; Akolpoğlu, Mükrime Birgül; İnceoğlu, Yasemin; Kızılel, Seda; Master Student; Master Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 28376Emulsion-based generation of hydrogel particles has been widely explored for numerous applications in fields such as biomedical, food, and drug delivery. Water-in-water emulsion (w/w) is an organic solvent-free approach and exploits solely aqueous media to generate nano- or micropartides. This strategy is environment-friendly and favorable for biomedical applications where biocompatibility is the ultimate criterion. Hence, PEG-based microgels can be synthesized with desired size and functionality using w/w emulsion technique. To estimate the influence of emulsification parameters on size and stability of PEG-lipid microgels, optimizations using three independent input variables were carried out: (i) ultrasonication power, (ii) ultrasonication duration, and (iii) duration of light exposure. Physical immobilization of microgels on islet-organoids was achieved through hydrophobic interactions. Cell function and viability were assessed thoroughly after microgel immobilization. Microgel size is dependent on ultrasonication parameters and microgel stability is vastly determined by the duration of light exposure. Immobilization of microgels with 5 mM lipid moiety promoted coating of islet-organoids. Coated organoids retained their function and viability without significant adverse effects. This is important for understanding fundamental aspects of PEG-lipid microgels using w/w emulsion, useful for possible drug/gene delivery applications to increase treatment efficiency and ultimately lead to clinical translation of PEG microgels for biomedical applications.Publication Metadata only An ultra-compact and wireless tag for battery-free sweat glucose monitoring(Elsevier Advanced Technology, 2022) N/A; Department of Mechanical Engineering; N/A; N/A; Department of Mechanical Engineering; N/A; N/A; N/A; N/A; Department of Mechanical Engineering; Mirzajani, Hadi; Abbasiasl, Taher; Mirlou, Fariborz; İstif, Emin; Bathaei, Mohammad Javad; Dağ, Çağdaş; Deyneli, Oğuzhan; Dereli, Dilek Yazıcı; Beker, Levent; Researcher; PhD Student; PhD Student; Other; PhD Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID); n2STAR-Koç University Nanofabrication and Nanocharacterization Center for Scientifc and Technological Advanced Research; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; Graduate School of Sciences and Engineering; N/A; School of Medicine; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; 171914; 179659; 308798Glucose monitoring before, during, and after exercise is essential for people with diabetes as exercise increases the risk of activity-induced hyper- and hypo-glycemic events. The situation is even more challenging for athletes with diabetes as they have impaired metabolic control compared to sedentary individuals. In this regard, a compact and noninvasive wearable glucose monitoring device that can be easily worn is critical to enabling glucose monitoring. This report presents an ultra-compact glucose tag with a footprint and weight of 1.2 cm(2) and 0.13 g, respectively, for sweat analysis. The device comprises a near field communication (NFC) chip, antenna, electrochemical sensor, and microfluidic channels implemented in different material layers. The device has a flexible and conformal structure and can be easily attached to different body parts. The battery-less operation of the device was enabled by NFC-based wireless power transmission and the compact antenna. Femtosecond laser ablation was employed to fabricate a highly compact and flexible NFC antenna. The proposed device demonstrated excellent operating characteristics with a limit of detection (LOD), limit of quantification (LOQ), and sensitivity of 24 mu M, 74 mu M, and 1.27 mu A cm(-2) mM(-1), respectively. The response of the proposed sensor in sweat glucose detection and quantification was validated by nuclear magnetic resonance spectroscopy (NMR). Also, the device's capability in attachment to the body, sweat collection, and glucose measurement was demonstrated through in vitro and in vivo experiments, and satisfactory results were obtained.Publication Metadata only Anharmonicity, mode-coupling and entropy in a fluctuating native protein(Iop Publishing Ltd, 2010) N/A; Department of Physics; Department of Computer Engineering; N/A; Department of Chemical and Biological Engineering; Kabakçıoğlu, Alkan; Yüret, Deniz; Gür, Mert; Erman, Burak; Faculty Member; Faculty Member; PhD Student; Faculty Member; Department of Physics; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Sciences; College of Engineering; Graduate School of Sciences and Engineering; College of Engineering; 49854; 179996; 216930; 179997We develop a general framework for the analysis of residue fluctuations that simultaneously incorporates anharmonicity and mode-coupling in a unified formalism. We show that both deviations from the Gaussian model are important for modeling the multidimensional energy landscape of the protein Crambin (1EJG) in the vicinity of its native state. the effect of anharmonicity and mode-coupling on the fluctuational entropy is in the order of a few percent.Publication Metadata only Applications of deep learning to the assessment of red blood cell deformability(IOS Press, 2021) Turgut, Alper; N/A; Yalçın, Özlem; Faculty Member; School of Medicine; 218440BACKGROUND: Measurement of abnormal Red Blood Cell (RBC) deformability is a main indicator of Sickle Cell Anemia (SCA) and requires standardized quantification methods. Ektacytometry is commonly used to estimate the fraction of Sickled Cells (SCs) by measuring the deformability of RBCs from laser diffraction patterns under varying shear stress. In addition to estimations from model comparisons, use of maximum Elongation Index differences (Delta EImax) at different laser intensity levels was recently proposed for the estimation of SC fractions. OBJECTIVE: Implement a convolutional neural network to accurately estimate rigid-cell fraction and RBC concentration from laser diffraction patterns without using a theoretical model and eliminating the ektacytometer dependency for deformability measurements. METHODS: RBCs were collected from control patients. Rigid-cell fraction experiments were performed using varying concentrations of glutaraldehyde. Serial dilutions were used for varying the concentration of RBC. A convolutional neural network was constructed using Python and TensorFlow. RESULTS and CONCLUSIONS: Measurements and model predictions show that a linear relationship between Delta EImax and rigid-cell fraction exists only for rigid-cell fractions less than 0.2. The proposed neural network architecture can be used successfully for both RBC concentration and rigid-cell fraction estimations without a need for a theoretical model.Publication Metadata only Coherent organization in gene regulation: a study on six networks(Iop Publishing Ltd, 2016) N/A; Department of Physics; Aral, Neşe; Kabakçıoğlu, Alkan; PhD Student; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854Structural and dynamical fingerprints of evolutionary optimization in biological networks are still unclear. Here we analyze the dynamics of genetic regulatory networks responsible for the regulation of cell cycle and cell differentiation in three organisms or cell types each, and show that they follow a version of Hebb's rule which we have termed coherence. More precisely, we find that simultaneously expressed genes with a common target are less likely to act antagonistically at the attractors of the regulatory dynamics. We then investigate the dependence of coherence on structural parameters, such as the mean number of inputs per node and the activatory/repressory interaction ratio, as well as on dynamically determined quantities, such as the basin size and the number of expressed genes.Publication Metadata only Coherent regulation in yeast's cell-cycle network(Iop Publishing Ltd, 2015) N/A; Department of Physics; Aral, Neşe; Kabakçıoğlu, Alkan; PhD Student; Faculty Member; Department of Physics; Graduate School of Sciences and Engineering; College of Sciences; N/A; 49854We define a measure of coherent activity for gene regulatory networks, A property that reflects the unity of purpose between the regulatory agents with a common target. We propose that such harmonious regulatory action is desirable under a demand for energy efficiency and may be selected for under evolutionary pressures. We consider two recent models of the cell-cycle regulatory network of the yeast, Saccharomyces cerevisiae as a case study and calculate their degree of coherence. a comparison with random networks of similar size and composition reveals that the yeast's cell-cycle regulation is wired to yield an exceptionally high level of coherent regulatory activity. We also investigate the mean degree of coherence as a function of the network size, connectivity and the fraction of repressory/activatory interactions.Publication Metadata only Combining protein-protein interaction networks with structures(Cell Press, 2009) Nussinov, Ruth; N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Kar, Gözde; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; N/A; 8745; 26605Publication Metadata only Computational and experimental investigation of DNA repair protein photolyase interactions with low molecular weight drugs(Wiley-Blackwell, 2013) Marusic, Maja; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Azizoğlu, Selimcan; Kızılel, Rıza; Kavaklı, İbrahim Halil; Erman, Burak; Kızılel, Seda; Master Student; Researcher; Faculty Member; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; College of Engineering; College of Engineering; N/A; 114475; 40319; 179997; 28376This paper reports the previously unknown interactions between eight low molecular weight commercially available drugs (130800Da) and DNA repair protein photolyase using computational docking simulations and surface plasmon resonance (SPR) experiments. Theoretical dissociation constants, Kd, obtained from molecular docking simulations were compared with the values found from SPR experiments. Among the eight drugs analyzed, computational and experimental values showed similar binding affinities between selected drug and protein pairs. We found no significant differences in binding interactions between pure and commercial forms of the drug lornoxicam and DNA photolyase. Among the eight drugs studied, prednisone, desloratadine, and azelastine exhibited the highest binding affinity (Kd=1.65, 2.05, and 8.47M, respectively) toward DNA photolyase. Results obtained in this study are promising for use in the prediction of unknown interactions of common drugs with specific proteins such as human clock protein cryptochrome. Copyright (c) 2013 John Wiley & Sons, Ltd.