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Publication Open Access 3D printed microneedles for point of care biosensing applications(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Department of Mechanical Engineering; Sarabi, Misagh Rezapour; Nakhjavani, Sattar Akbar; Taşoğlu, Savaş; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 291971Microneedles (MNs) are an emerging technology for user-friendly and minimally invasive injection, offering less pain and lower tissue damage in comparison to conventional needles. With their ability to extract body fluids, MNs are among the convenient candidates for developing biosensing setups, where target molecules/biomarkers are detected by the biosensor using the sample collected with the MNs. Herein, we discuss the 3D printing of microneedle arrays (MNAs) toward enabling point-of-care (POC) biosensing applications.Publication Open Access A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells(Nature Publishing Group (NPG), 2018) Seferoğlu, Ayşe Bengisu; Department of Molecular Biology and Genetics; Dunn, Cory David; Keskin, Abdurrahman; Akdoğan, Emel; Lutfullahoglu-Bal, Guleycan; Department of Molecular Biology and Genetics; College of SciencesProkaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential in the era of eukaryogenesis. Since eukaryotes are highly compartmentalized, it is worthwhile to consider the mechanisms by which newly transferred proteins might reach diverse organellar destinations. Toward this goal, we have focused our attention upon the behavior of bacteria-derived tail anchors (TAs) expressed in the eukaryote Saccharomyces cerevisiae. In this study, we report that a predicted membrane-associated domain of the Escherichia coli YgiM protein is specifically trafficked to peroxisomes in budding yeast, can be found at a pre-peroxisomal compartment (PPC) upon disruption of peroxisomal biogenesis, and can functionally replace an endogenous, peroxisome-directed TA. Furthermore, the YgiM(TA) can localize to peroxisomes in mammalian cells. Since the YgiM(TA) plays no endogenous role in peroxisomal function or assembly, this domain is likely to serve as an excellent tool allowing further illumination of the mechanisms by which TAs can travel to peroxisomes. Moreover, our findings emphasize the ease with which bacteria-derived sequences might target to organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.
Publication Metadata only A front-tracking method for computational modeling of viscoelastic two-phase flow systems(Elsevier, 2015) N/A; N/A; Department of Mechanical Engineering; Izbassarov, Daulet; Muradoğlu, Metin; PhD Student; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 46561A front-tracking method is developed for direct numerical simulations of viscoelastic two-phase systems in which one or both phases could be viscoelastic. One set of governing equations is written for the whole computational domain and different phases are treated as a single fluid with variable material and rheological properties. The interface is tracked explicitly using a Lagrangian grid while the flow equations are solved on a fixed Eulerian grid. The surface tension is computed at the interface using the Lagrangian grid and included into the momentum equations as a body force. The Oldroyd-B, FENE-CR and FENE-MCR models are employed to model the viscoelasticity. The viscoelastic model equations are solved fully coupled with the flow equations within the front-tracking framework. A fifth-order WENO scheme is used to approximate the convective terms in the viscoelastic model equations and second-order central differences are used for all other spatial derivatives. A log-conformation method-is employed to alleviate the high Weissenberg number problem (HWNP) and found to be stable and very robust for a wide range of Weissenberg numbers. The method has been first validated for various benchmark single-phase and two-phase viscoelastic flow problems. Then it has been applied to study motion and deformation of viscoelastic two-phase systems in a pressure-driven flow through a capillary tube with a sudden contraction and expansion. The method has been demonstrated to be grid convergent with second-order spatial accuracy for all the cases considered in this paper.Publication Open Access A new RIS architecture with a single power amplifier: energy efficiency and error performance analysis(Institute of Electrical and Electronics Engineers (IEEE), 2022) Alexandropoulos, George C.; Department of Electrical and Electronics Engineering; Başar, Ertuğrul; Taşçı, Recep Akif; Kılınç, Fatih; Faculty Member; Master Student; Researcher; Department of Electrical and Electronics Engineering; Graduate School of Sciences and Engineering; College of Engineering; 149116; N/A; N/AMany electrochemical devices are based on the fundamental process of ion migration and accumulation on surfaces. Complex interplay of molecular properties of ions and device dimensions control the entire process and define the overall dynamics of the system. Particularly, for ionic liquid-based electrolytes it is often not clear which property, and to what extent, contributes to the overall performance of the device. Herein we use X-ray photoelectron spectroscopy (XPS) while the device is under electrical bias. Such a procedure reveals localized electrical potential developments, through binding energy shifts of the atomic core levels, in a chemically specific fashion. Combining it with square-wave AC modulation, the information can also be extended to time domain, and we investigate devices configured as a coplanar capacitor, with an ionic liquid as the electrolyte, in macro-dimensions. Our analysis reveals that a nonlinear voltage profile across the device emerges from spatially non-uniform electrical double layer formation on electrode surfaces. Interestingly the coplanar capacitor has an extremely slow time response which is particularly controlled by IL film thickness. XPS measurements can capture the ion dynamics in the tens of seconds to microseconds range, and reveal that ionic motion is all over the device, including on metallic electrode regions. This behavior can only be attributed to motion in more than one dimension. The ion dynamics can also be faithfully simulated by using a modified PNP equation, taking into account steric effects, and device dimensions. XPS measurements on two devices with different dimensions corroborated and validated the simulation results. The present results propose a new experimental approach and provide new insights into the dynamics of ions across electrochemical devices.Publication Open Access A novel method for PEGylation of chitosan nanoparticles through photopolymerization(Royal Society of Chemistry (RSC), 2019) Department of Chemical and Biological Engineering; Bozüyük, Uğur; Gökulu, İpek Simay; Doğan, Nihal Olcay; Kızılel, Seda; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; N/A; N/A; N/A; 28376An ultrafast and convenient method for PEGylation of chitosan nanoparticles has been established through a photopolymerization reaction between the acrylate groups of PEG and methacrylated-chitosan nanoparticles. The nanoparticle characteristics under physiological pH conditions were optimized through altered PEG chain length, concentration and duration of UV exposure. The method developed here has potential for clinical translation of chitosan nanoparticles. It also allows for the scalable and fast synthesis of nanoparticles with colloidal stability.Publication Open Access A queueing-theoretical delay analysis for intra-body nervous nanonetwork(Elsevier, 2015) Department of Electrical and Electronics Engineering; Abbasi, Naveed Ahmed; Akan, Özgür Barış; Faculty Member; Department of Electrical and Electronics Engineering; College of EngineeringNanonetworks is an emerging field of study where nanomachines communicate to work beyond their individual limited processing capabilities and perform complicated tasks. The human body is an example of a very large nanoscale communication network, where individual constituents communicate by means of molecular nanonetworks. Amongst the various intra-body networks, the nervous system forms the largest and the most complex network. In this paper, we introduce a queueing theory based delay analysis model for neuro-spike communication between two neurons. Using standard queueing model blocks such as servers, queues and fork-join networks, impulse reception and processing through the nervous system is modeled as arrival and service processes in queues. Simulations show that the response time characteristics of the model are comparable to those of the biological neurons.Publication Open Access A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition(Nature Publishing Group (NPG), 2020) Christodoulou, Michael S.; Güzelcan, Ece Akhan; Koyaş, Altay; Karaca, Çiğdem; Passarella, Daniele; Çetin-Atalay, Rengül; Şahin, İrem Durmaz; Faculty Member; School of Medicine; 303825Hepatocellular carcinoma (HCC) ranks as the fifth most common and the second deadliest cancer worldwide. HCC is extremely resistant to the conventional chemotherapeutics. Hence, it is vital to develop new treatment options. Chalcones were previously shown to have anticancer activities in other cancer types. In this study, 11 chalcones along with quercetin, papaverin, catechin, Sorafenib and 5FU were analyzed for their bioactivities on 6 HCC cell lines and on dental pulp stem cells (DPSC) which differentiates into hepatocytes, and is used as a model for untransformed control cells. 3 of the chalcones (1, 9 and 11) were selected for further investigation due to their high cytotoxicity against liver cancer cells and compared to the other clinically established compounds. Chalcones did not show significant bioactivity (IC 50> 20 μ M) on dental pulp stem cells. Cell cycle analysis revealed that these 3 chalcone-molecules induced SubG1/G1 arrest. Akt protein phosphorylation was inhibited by these molecules in PTEN deficient, drug resistant, mesenchymal like Mahlavu cells leading to the activation of p21 and the inhibition of NFκB-p65 transcription factor. Hence the chalcones induced apoptotic cell death pathway through NFκB-p65 inhibition. On the other hand, these molecules triggered p21 dependent activation of Rb protein and thereby inhibition of cell cycle and cell growth in liver cancer cells. Involvement of PI3K/Akt pathway hyperactivation was previously described in survival of liver cancer cells as carcinogenic event. Therefore, our results indicated that these chalcones can be considered as candidates for liver cancer therapeutics particularly when PI3K/Akt pathway involved in tumor development.Publication Open Access A subspace method for large-scale eigenvalue optimization(Society for Industrial and Applied Mathematics (SIAM), 2018) Meerbergen, Karl; Michiels, Wim; Department of Mathematics; Kangal, Fatih; Mengi, Emre; Faculty Member; Department of Mathematics; College of Sciences; Graduate School of Sciences and Engineering; N/A; 113760We consider the minimization or maximization of the Jth largest eigenvalue of an analytic and Hermitian matrix-valued function, and build on Mengi, Yildirim, and Kilic [SIAM T. Matrix Anal. Appl., 35, pp. 699-724, 2014]. This work addresses the setting when the matrix-valued function involved is very large. We describe subspace procedures that convert the original problem into a small-scale one by means of orthogonal projections and restrictions to certain subspaces, and that gradually expand these subspaces based on the optimal solutions of small-scale problems. Global convergence and superlinear rate-of-convergence results with respect to the dimensions of the subspaces are presented in the infinite dimensional setting, where the matrix-valued function is replaced by a compact operator depending on parameters. In practice, it suffices to solve eigenvalue optimization problems involving matrices with sizes on the scale of tens, instead of the original problem involving matrices with sizes on the scale of thousands.Publication Metadata only Adaptation strategies for MGS scalable video streaming(Elsevier, 2012) N/A; Department of Electrical and Electronics Engineering; Görkemli, Burak; Tekalp, Ahmet Murat; N/A; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; College of Engineering; N/A; 26207An adaptive streaming framework consists of a video codec that can produce video encoded at a variety of rates, a transport protocol that supports an effective rate/congestion control mechanism, and an adaptation strategy in order to match the video source rate to the available network throughput. The main parameters of the adaptation strategy are encoder configuration, video extraction method, determination of video extraction rate, send rate control, retransmission of lost packets, decoder buffer status, and packetization method. This paper proposes optimal adaptation strategies, in terms of received video quality and used network resources, at the codec and network levels using a medium grain scalable (MGS) video codec and two transport protocols with built-in congestion control, TCP and DCCP. Key recommendations are presented to obtain the best results in adaptive video streaming using TCP or DCCP based on extensive experimental results over the Internet. (c) 2012 Elsevier B.V. All rights reserved.Publication Open Access AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation(BioMed Central, 2021) Philpott, Martin; Oppermann, Udo; Department of Molecular Biology and Genetics; Önder, Tamer Tevfik; Uğurlu Çimen, Deniz; Sevinç, Kenan; Küçük, Nazlı Ezgi Özkan; Özçimen, Burcu; Demirtaş, Deniz; Enüstün, Eray; Faculty Member; Faculty Member; PhD Student; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; College of Sciences; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; 42946; 105301; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/ABackground: the histone H3 lysine 79 (H3K79) methyltransferase DOT1L is a key chromatin-based barrier to somatic cell reprogramming. However, the mechanisms by which DOT1L safeguards cell identity and somatic-specific transcriptional programs remain unknown. Results: we employed a proteomic approach using proximity-based labeling to identify DOT1L-interacting proteins and investigated their effects on reprogramming. Among DOT1L interactors, suppression of AF10 (MLLT10) via RNA interference or CRISPR/Cas9, significantly increases reprogramming efficiency. In somatic cells and induced pluripotent stem cells (iPSCs) higher order H3K79 methylation is dependent on AF10 expression. In AF10 knock-out cells, re-expression wild-type AF10, but not a DOT1L binding-impaired mutant, rescues overall H3K79 methylation and reduces reprogramming efficiency. Transcriptomic analyses during reprogramming show that AF10 suppression results in downregulation of fibroblast-specific genes and accelerates the activation of pluripotency-associated genes. Conclusions: our findings establish AF10 as a novel barrier to reprogramming by regulating H3K79 methylation and thereby sheds light on the mechanism by which cell identity is maintained in somatic cells.