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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Nanoscale communication with molecular arrays in nanonetworks(Institute of Electrical and Electronics Engineers (IEEE), 2012) Galmes, Sebastia; Atakan, Barış; Akan, Özgür Barış; PhD Student; Faculty Member; College of EngineeringMolecular communication is a promising nanoscale communication paradigm that enables nanomachines to exchange information by using molecules as communication carrier. Up to now, the molecular communication channel between a transmitter nanomachine (TN) and a receiver nanomachine (RN) has been modeled as either concentration channel or timing channel. However, these channel models necessitate exact time synchronization of the nanomachines and provide a relatively low communication bandwidth. In this paper, the Molecular ARray-based COmmunication (MARCO) scheme is proposed, in which the transmission order of different molecules is used to convey molecular information without any need for time synchronization. The MARCO channel model is first theoretically derived, and the intersymbol interference and error probabilities are obtained. Based on the error probability, achievable communication rates are analytically obtained. Numerical results and performance comparisons reveal that MARCO provides significantly higher communication rate, i.e., on the scale of 100 Kbps, than the previously proposed molecular communication models without any need for synchronization. More specifically, MARCO can provide more than 250 Kbps of molecular communication rate if intersymbol time and internode distance are set to 2 mu s and 2 nm, respectively.Publication Open Access Efficient photocapacitors via ternary hybrid photovoltaic optimization for photostimulation of neurons(Optical Society of America (OSA), 2020) Department of Electrical and Electronics Engineering; Srivastava, Shashi Bhushan; Melikov, Rustamzhon; Yıldız, Erdost; Han, Mertcan; Şahin, Afsun; Nizamoğlu, Sedat; Researcher; PhD Student; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Electrical and Electronics Engineering; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 171267; 130295Optoelectronic photoelectrodes based on capacitive charge-transfer offer an attractive route to develop safe and effective neuromodulators. Here, we demonstrate efficient optoelectronic photoelectrodes that are based on the incorporation of quantum dots (QDs) into poly(3-hexylthiophene-2,5-diyl) (P3HT) and [6,6]-Phenyl-C61-butyric acid methyl ester (PCBM) bulk heterojunction. We control the performance of the photoelectrode by the blend ratio, thickness, and nanomorphology of the ternary bulk heterojunction. The optimization led to a photocapacitor that has a photovoltage of 450 mV under a light intensity level of 20 mW.cm(-2) and a responsivity of 99 mA/W corresponding to the most light-sensitive organic photoelectrode reported to date. The photocapacitor can facilitate action potential generation by hippocampal neurons via burst waveforms at an intensity level of 20 mW.cm(-2). Therefore, the results point to an alternative direction in the engineering of safe and ultra-light-sensitive neural interfaces.Publication Open Access 3D spatial organization and network-guided comparison of mutation profiles in Glioblastoma reveals similarities across patients(Public Library of Science, 2019) Dinçer, Cansu; Kaya, Tuğba; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; Department of Computer Engineering; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; 26605; 8745Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor. Molecular heterogeneity is a hallmark of GBM tumors that is a barrier in developing treatment strategies. In this study, we used the nonsynonymous mutations of GBM tumors deposited in The Cancer Genome Atlas (TCGA) and applied a systems level approach based on biophysical characteristics of mutations and their organization in patient-specific subnetworks to reduce inter-patient heterogeneity and to gain potential clinically relevant insights. Approximately 10% of the mutations are located in "patches" which are defined as the set of residues spatially in close proximity that are mutated across multiple patients. Grouping mutations as 3D patches reduces the heterogeneity across patients. There are multiple patches that are relatively small in oncogenes, whereas there are a small number of very large patches in tumor suppressors. Additionally, different patches in the same protein are often located at different domains that can mediate different functions. We stratified the patients into five groups based on their potentially affected pathways, revealed from the patient-specific subnetworks. These subnetworks were constructed by integrating mutation profiles of the patients with the interactome data. Network-guided clustering showed significant association between each group and patient survival (P-value = 0.0408). Also, each group carries a set of signature 3D mutation patches that affect predominant pathways. We integrated drug sensitivity data of GBM cell lines with the mutation patches and the patient groups to analyze the therapeutic outcome of these patches. We found that Pazopanib might be effective in Group 3 by targeting CSF1R. Additionally, inhibiting ATM that is a mediator of PTEN phosphorylation may be ineffective in Group 2. We believe that from mutations to networks and eventually to clinical and therapeutic data, this study provides a novel perspective in the network-guided precision medicine.Publication Open Access A cartridge based sensor array platform for multiple coagulation measurements from plasma(Royal Society of Chemistry (RSC), 2015) Bulut, Serpil; Yaralioglu, G. G.; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Çakmak, Onur; Ermek, Erhan; Kılınç, Necmettin; Barış, İbrahim; Kavaklı, İbrahim Halil; Ürey, Hakan; PhD Student; Other; Researcher; Teaching Faculty; Faculty Member; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; 109991; N/A; 111629; 40319; 8579This paper proposes a MEMS-based sensor array enabling multiple clot-time tests for plasma in one disposable microfluidic cartridge. The versatile LoC (Lab-on-Chip) platform technology is demonstrated here for real-time coagulation tests (activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)). The system has a reader unit and a disposable cartridge. The reader has no electrical connections to the cartridge. This enables simple and low-cost cartridge designs and avoids reliability problems associated with electrical connections. The cartridge consists of microfluidic channels and MEMS microcantilevers placed in each channel. The microcantilevers are made of electroplated nickel. They are actuated remotely using an external electro-coil and the read-out is also conducted remotely using a laser. The phase difference between the cantilever oscillation and the coil drive is monitored in real time. During coagulation, the viscosity of the blood plasma increases resulting in a change in the phase read-out. The proposed assay was tested on human and control plasma samples for PT and aPTT measurements. PT and aPTT measurements from control plasma samples are comparable with the manufacturer's datasheet and the commercial reference device. The measurement system has an overall 7.28% and 6.33% CV for PT and aPTT, respectively. For further implementation, the microfluidic channels of the cartridge were functionalized for PT and aPTT tests by drying specific reagents in each channel. Since simultaneous PT and aPTT measurements are needed in order to properly evaluate the coagulation system, one of the most prominent features of the proposed assay is enabling parallel measurement of different coagulation parameters. Additionally, the design of the cartridge and the read-out system as well as the obtained reproducible results with 10 mu l of the plasma samples suggest an opportunity for a possible point-of-care application.Publication Open Access Detection of biological switches using the method of Groebner bases(BioMed Central, 2019) Department of Chemical and Biological Engineering; Arkun, Yaman; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 108526Background: bistability and ability to switch between two stable states is the hallmark of cellular responses. Cellular signaling pathways often contain bistable switches that regulate the transmission of the extracellular information to the nucleus where important biological functions are executed. Results in this work we show how the method of Groebner bases can be used to detect bistability and output switchability. The method of Groebner bases can be seen as a multivariate, non-linear generalization of the Gaussian elimination for linear systems which conveniently seperates the variables and drastically simplifies the simultaneous solution of polynomial equations. A necessary condition for fixed-point state bistability is for the Grobner basis to have three distinct solutions for the state. A sufficient condition is provided by the eigenvalues of the local Jacobians. We also introduce the concept of output switchability which is defined as the ability of an output of a bistable system to switch between two different stable steady-state values. It is shown that bistability does not necessarily guarantee switchability of every state variable of the system. We further show that, for a bistable system, the necessary conditions for output switchability can be derived using the Groebner basis. The theoretical results are incorporated into an analysis procedure and applied to several systems including the AKT (Protein kinase B), RAS (Rat Sarcoma) and MAPK (Mitogen-activated protein kinase) signal transduction pathways. Results demonstrate that the Groebner bases can be conveniently used to analyze biological switches by simultaneously detecting bistability and output switchability. Conclusion: the Groebner bases provides a novel methodology to analyze bistability. Results clarify the distinction between bistability and output switchability which is lacking in the literature. We have shown that theoretically, it is possible to have an output subspace of an n-dimensional bistable system where certain variables cannot switch. It is possible to construct such systems as we have done with two reaction networks.Publication Open Access Applications of augmented reality in ophthalmology [invited](Optical Society of America (OSA), 2021) Artal, Pablo; Department of Physics; Department of Electrical and Electronics Engineering; Aydındoğan, Güneş; Kavaklı, Koray; Ürey, Hakan; Şahin, Afsun; Faculty Member; Faculty Member; Department of Physics; Department of Electrical and Electronics 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; 8579; 171267Throughout the last decade, augmented reality (AR) head-mounted displays (HMDs) have gradually become a substantial part of modern life, with increasing applications ranging from gaming and driver assistance to medical training. Owing to the tremendous progress in miniaturized displays, cameras, and sensors, HMDs are now used for the diagnosis, treatment, and follow-up of several eye diseases. In this review, we discuss the current state-of-the-art as well as potential uses of AR in ophthalmology. This review includes the following topics: (i) underlying optical technologies, displays and trackers, holography, and adaptive optics; (ii) accommodation, 3D vision, and related problems such as presbyopia, amblyopia, strabismus, and refractive errors; (iii) AR technologies in lens and corneal disorders, in particular cataract and keratoconus; (iv) AR technologies in retinal disorders including age-related macular degeneration (AMD), glaucoma, color blindness, and vision simulators developed for other types of low-vision patients.Publication Open Access Machine learning-enabled multiplexed microfluidic sensors(American Institute of Physics (AIP) Publishing, 2020) Yetişen, Ali Kemal; N/A; Department of Mechanical Engineering; Department of Electrical and Electronics Engineering; Dabbagh, Sajjad Rahmani; Rabbi, Fazle; Doğan, Zafer; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; Department of Electrical and Electronics 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); Graduate School of Social Sciences and Humanities; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 280658; 291971High-throughput, cost-effective, and portable devices can enhance the performance of point-of-care tests. Such devices are able to acquire images from samples at a high rate in combination with microfluidic chips in point-of-care applications. However, interpreting and analyzing the large amount of acquired data is not only a labor-intensive and time-consuming process, but also prone to the bias of the user and low accuracy. Integrating machine learning (ML) with the image acquisition capability of smartphones as well as increasing computing power could address the need for high-throughput, accurate, and automatized detection, data processing, and quantification of results. Here, ML-supported diagnostic technologies are presented. These technologies include quantification of colorimetric tests, classification of biological samples (cells and sperms), soft sensors, assay type detection, and recognition of the fluid properties. Challenges regarding the implementation of ML methods, including the required number of data points, image acquisition prerequisites, and execution of data-limited experiments are also discussed.Publication Open Access Tipping the scale from disorder to alpha-helix: folding of amphiphilic peptides in the presence of macroscopic and molecular interfaces(Public Library of Science, 2015) Globisch, Christoph; Peter, Christine; N/A; Department of Mechanical Engineering; Dalgıçdır, Cahit; Sayar, Mehmet; PhD Student; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 109820Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK) and EAA LAEALAEALAE (EALA), with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides' response to macroscopic and molecular interfaces (presented by an aggregation partner) can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides' aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.Publication Open Access Machine learning helps identify CHRONO as a circadian clock component(Public Library of Science, 2014) Anafi, Ron C.; Lee, Yoo; Sato, Trey K.; Venkataraman, Anand; Ramanathan, Chidambaram; Hughes, Michael E.; Baggs, Julie E.; Growe, Jacqueline; Liu, Andrew C.; Kim, Junhyong; Hogenesch, John B.; Kavaklı, İbrahim Halil; Faculty Member; College of Engineering; 40319Over the last decades, researchers have characterized a set of ‘‘clock genes’’ that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator). Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics.Publication Open Access Classification of drug molecules considering their IC(50) values using mixed-integer linear programming based hyper-boxes method(BioMed Central, 2008) Department of Industrial Engineering; Department of Chemical and Biological Engineering; Armutlu, Pelin; Özdemir, Muhittin Emre; Yüksektepe, Fadime Üney; Kavaklı, İbrahim Halil; Türkay, Metin; Faculty Member; Department of Industrial Engineering; Department of Chemical and Biological Engineering; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; N/A; N/A; N/A; 40319; 24956Background: A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC(50) values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. Results: We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC(50) values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naive Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Conclusion: Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed.