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    PublicationOpen Access
    Fabrication and microfluidic analysis of graphene-based molecular communication receiver for Internet of Nano Things (IoNT)
    (Springer Nature, 2021) Ramezani, Hamideh; Dinç, Ergin; Akhavan, Shahab; Department of Electrical and Electronics Engineering; Akan, Özgür Barış; Kuşcu, Murat; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; 6647; 316349
    Bio-inspired molecular communications (MC), where molecules are used to transfer information, is the most promising technique to realise the Internet of Nano Things (IoNT), thanks to its inherent biocompatibility, energy-efficiency, and reliability in physiologically-relevant environments. Despite a substantial body of theoretical work concerning MC, the lack of practical micro/nanoscale MC devices and MC testbeds has led researchers to make overly simplifying assumptions about the implications of the channel conditions and the physical architectures of the practical transceivers in developing theoretical models and devising communication methods for MC. On the other hand, MC imposes unique challenges resulting from the highly complex, nonlinear, time-varying channel properties that cannot be always tackled by conventional information and communication tools and technologies (ICT). As a result, the reliability of the existing MC methods, which are mostly adopted from electromagnetic communications and not validated with practical testbeds, is highly questionable. As the first step to remove this discrepancy, in this study, we report on the fabrication of a nanoscale MC receiver based on graphene field-effect transistor biosensors. We perform its ICT characterisation in a custom-designed microfluidic MC system with the information encoded into the concentration of single-stranded DNA molecules. This experimental platform is the first practical implementation of a micro/nanoscale MC system with nanoscale MC receivers, and can serve as a testbed for developing realistic MC methods and IoNT applications.
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    PublicationOpen Access
    Modeling convection-diffusion-reaction systems for microfluidic molecular communications with surface-based receivers in Internet of Bio-Nano Things
    (Public Library of Science, 2018) Department of Electrical and Electronics Engineering; Kuşcu, Murat; Akan, Özgür Barış; Faculty Member; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; Graduate School of Sciences and Engineering
    We consider a microfluidic molecular communication (MC) system, where the concentration-encoded molecular messages are transported via fluid flow-induced convection and diffusion, and detected by a surface-based MC receiver with ligand receptors placed at the bottom of the microfluidic channel. The overall system is a convection-diffusion-reaction system that can only be solved by numerical methods, e.g., finite element analysis (FEA). However, analytical models are key for the information and communication technology (ICT), as they enable an optimisation framework to develop advanced communication techniques, such as optimum detection methods and reliable transmission schemes. In this direction, we develop an analytical model to approximate the expected time course of bound receptor concentration, i.e., the received signal used to decode the transmitted messages. The model obviates the need for computationally expensive numerical methods by capturing the nonlinearities caused by laminar flow resulting in parabolic velocity profile, and finite number of ligand receptors leading to receiver saturation. The model also captures the effects of reactive surface depletion layer resulting from the mass transport limitations and moving reaction boundary originated from the passage of finite-duration molecular concentration pulse over the receiver surface. Based on the proposed model, we derive closed form analytical expressions that approximate the received pulse width, pulse delay and pulse amplitude, which can be used to optimize the system from an ICT perspective. We evaluate the accuracy of the proposed model by comparing model-based analytical results to the numerical results obtained by solving the exact system model with COMSOL Multiphysics.
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    PublicationOpen Access
    Modelling and analysis of the impact of correlated inter-event data on production control using Markovian arrival processes
    (Springer, 2019) Department of Business Administration; Department of Industrial Engineering; N/A; Tan, Barış; Dizbin, Nima Manafzadeh; Faculty Member; Department of Business Administration; Department of Industrial Engineering; College of Administrative Sciences and Economics; College of Engineering; Graduate School of Business; 28600; N/A
    Empirical studies show that the inter-event times of a production system are correlated. However, most of the analytical studies for the analysis and control of production systems ignore correlation. In this study, we show that real-time data collected from a manufacturing system can be used to build a Markovian arrival processes (MAP) model that captures correlation in inter-event times. The obtained MAP model can then be used to control production in an effective way. We first present a comprehensive review on MAP modeling and MAP fitting methods applicable to manufacturing systems. Then we present results on the effectiveness of these fitting methods and discuss how the collected inter-event data can be used to represent the flow dynamics of a production system accurately. In order to study the impact of capturing the flow dynamics accurately on the performance of a production control system, we analyze a manufacturing system that is controlled by using a base-stock policy. We study the impact of correlation in inter-event times on the optimal base-stock level of the system numerically by employing the structural properties of the MAP. We show that ignoring correlated arrival or service process can lead to overestimation of the optimal base-stock level for negatively correlated processes, and underestimation for the positively correlated processes. We conclude that MAPs can be used to develop data-driven models and control manufacturing systems more effectively by using shop-floor inter-event data.
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    PublicationOpen Access
    The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD
    (Nature Publishing Group (NPG), 2022) Günsel, Gizem Güneş; Conlon, Thomas M.; Jeridi, Aicha; Kim, Rinho; Ertuez, Zeynep; Lang, Niklas J.; Ansari, Meshal; Novikova, Mariia; Jiang, Dongsheng; Strunz, Maximilian; Gaianova, Mariia; Hollauer, Christine; Gabriel, Christina; Angelidis, Ilias; Doll, Sebastian; Pestoni, Jeanine C.; Edelmann, Stephanie L.; Kohlhepp, Marlene Sophia; Guillot, Adrien; Bassler, Kevin; Van Eeckhoutte, Hannelore P.; Kanashova, Tamara; Rodius, Sophie; Ballester-Lopez, Carolina; Robles, Carlos M. Genes; Smirnova, Natalia; Rehberg, Markus; Agarwal, Charu; Krikki, Ioanna; Piavaux, Benoit; Verleden, Stijn E.; Vanaudenaerde, Bart; Koenigshoff, Melanie; Dittmar, Gunnar; Bracke, Ken R.; Schultze, Joachim L.; Watz, Henrik; Eickelberg, Oliver; Stoeger, Tobias; Burgstaller, Gerald; Tacke, Frank; Heissmeyer, Vigo; Rinkevich, Yuval; Schiller, Herbert B.; Conrad, Marcus; Schneider, Robert; Kayalar, Özgecan; Konyalılar, Nur; Bayram, Hasan; Yıldırım, Ali Önder; Researcher; PhD Student; Faculty Member; Other; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; 4890; N/A
    Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that in chronic obstructive pulmonary disease (COPD) patients, PRMT7 expression is elevated in the lung tissue and localized to the macrophages. In mouse models of COPD, lung fibrosis and skin injury, reduced expression of PRMT7 associates with decreased recruitment of monocytes to the site of injury and hence less severe symptoms. Mechanistically, activation of NF-kappa B/RelA in monocytes induces PRMT7 transcription and consequential mono-methylation of histones at the regulatory elements of RAP1A, which leads to increased transcription of this gene that is responsible for adhesion and migration of monocytes. Persistent monocyte-derived macrophage accumulation leads to ALOX5 over-expression and accumulation of its metabolite LTB4, which triggers expression of ACSL4 a ferroptosis promoting gene in lung epithelial cells. Conclusively, inhibition of arginine mono-methylation might offer targeted intervention in monocyte-driven inflammatory conditions that lead to extensive tissue damage if left untreated. Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages.
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    PublicationOpen Access
    Cross-linguistic patterns in the acquisition of quantifiers
    (National Academy of Sciences, 2016) Katsos, Napoleon; Cummins, Chris; Ezeizabarrena, Maria-Jose; Gavarro, Anna; Kraljevic, Jelena Kuvac; Hrzica, Gordana; Grohmann, Kleanthes K.; Skordi, Athina; de Lopez, Kristine Jensen; Sundahl, Lone; van Hout, Angeliek; Hollebrandse, Bart; Overweg, Jessica; Faber, Myrthe; van Koert, Margreet; Smith, Nafsika; Vija, Maigi; Zupping, Sirli; Kunnari, Sari; Morisseau, Tiffany; Rusieshvili, Manana; Yatsushiro, Kazuko; Fengler, Anja; Varlokosta, Spyridoula; Konstantzou, Katerina; Farby, Shira; Guasti, Maria Teresa; Vernice, Mirta; Okabe, Reiko; Isobe, Miwa; Crosthwaite, Peter; Hong, Yoonjee; Balciuniene, Ingrida; Nizar, Yanti Marina Ahmad; Grech, Helen; Gatt, Daniela; Cheong, Win Nee; Asbjornsen, Arve; Torkildsen, Janne von Koss; Haman, Ewa; Miekisz, Aneta; Gagarina, Natalia; Puzanova, Julia; Andelkovic, Darinka; Savic, Maja; Josic, Smiljana; Slancova, Daniela; Kapalkova, Svetlana; Barberan, Tania; Hassan, Saima; Chan, Cecilia Yuet Hung; Okubo, Tomoya; van der Lely, Heather; Sauerland, Uli; Noveck, Ira; Department of Psychology; Özge, Duygu; Department of Psychology; College of Social Sciences and Humanities
    Learners of most languages are faced with the task of acquiring words to talk about number and quantity. Much is known about the order of acquisition of number words as well as the cognitive and perceptual systems and cultural practices that shape it. Substantially less is known about the acquisition of quantifiers. Here, we consider the extent to which systems and practices that support number word acquisition can be applied to quantifier acquisition and conclude that the two domains are largely distinct in this respect. Consequently, we hypothesize that the acquisition of quantifiers is constrained by a set of factors related to each quantifier's specific meaning. We investigate competence with the expressions for "all," "none," "some," "some. not," and "most" in 31 languages, representing 11 language types, by testing 768 5-y-old children and 536 adults. We found a cross-linguistically similar order of acquisition of quantifiers, explicable in terms of four factors relating to their meaning and use. In addition, exploratory analyses reveal that language-and learner-specific factors, such as negative concord and gender, are significant predictors of variation.
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    PublicationOpen Access
    De novo mutations in Plxnd1 and Rev3l cause mobius syndrome
    (Nature Publishing Group (NPG), 2015) Tomas-Roca, Laura; Tsaalbi-Shtylik, Anastasia; Jansen, Jacob G.; Singh, Manvendra K.; Epstein, Jonathan A.; Altunoglu, Umut; Verzijl, Harriette; Soria, Laura; van Beusekom, Ellen; Roscioli, Tony; Iqbal, Zafar; Gilissen, Christian; Hoischen, Alexander; de Brouwer,Arjan P. M.; Erasmus, Corrie; Schubert, Dirk; Brunner, Han; Aytes, Antonio Perez; Marin, Faustino; Aroca, Pilar; Carta, Arturo; de Wind, Niels; Padberg, George W.; van Bokhoven, Hans; N/A; Kayserili, Hülya; Other; School of Medicine; 7945
    Mobius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Mobius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients.
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    PublicationOpen Access
    Archaeometric evidence for the earliest exploitation of lignite from the bronze age Eastern Mediterranean
    (Nature Publishing Group (NPG), 2021) Buckley, Stephen; Power, Robert C.; Andreadaki-Vlazaki, Maria; Akar, Murat; Becher, Julia; Belser, Matthias; Cafisso, Sara; Eisenmann, Stefanie; Fletcher, Joann; Francken, Michael; Hallager, Birgitta; Harvati, Katerina; Kataki, Efthymia; Maran, Joseph; Martin, Mario A. S.; McGeorge, Photini J. P.; Milevski, Ianir; Papadimitriou, Alkestis; Protopapadaki, Eftychia; Salazar-Garcia, Domingo C.; Schmidt-Schultz, Tyede; Schuenemann, Verena J.; Shafiq, Rula; Stuijts, Ingelise; Yegorov, Dmitry; Yener, K. Aslıhan; Schultz, Michael; Spiteri, Cynthianne; Stockhammer, Philipp W.; Ingman, Tara; Researcher; Koç University Research Center for Anatolian Civilizations (ANAMED) / Anadolu Medeniyetleri Araştırma Merkezi (ANAMED)
    This paper presents the earliest evidence for the exploitation of lignite (brown coal) in Europe and sheds new light on the use of combustion fuel sources in the 2nd millennium BCE Eastern Mediterranean. We applied Thermal Desorption/Pyrolysis-Gas Chromatography-Mass Spectrometry and Polarizing Microscopy to the dental calculus of 67 individuals and we identified clear evidence for combustion markers embedded within this calculus. In contrast to the scant evidence for combustion markers within the calculus samples from Egypt, all other individuals show the inhalation of smoke from fires burning wood identified as Pinaceae, in addition to hardwood, such as oak and olive, and/or dung. Importantly, individuals from the Palatial Period at the Mycenaean citadel of Tiryns and the Cretan harbour site of Chania also show the inhalation of fire-smoke from lignite, consistent with the chemical signature of sources in the northwestern Peloponnese and Western Crete respectively. This first evidence for lignite exploitation was likely connected to and at the same time enabled Late Bronze Age Aegean metal and pottery production, significantly by both male and female individuals.
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    PublicationOpen Access
    Bioinspired cilia arrays with programmable nonreciprocal motion and metachronal coordination
    (American Association for the Advancement of Science (AAAS), 2020) Dong, Xiaoguang; Lum, Guo Zhan; Hu, Wenqi; Zhang, Rongjing; Ren, Ziyu; Onck, Patrick R.; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 297104
    Coordinated nonreciprocal dynamics in biological cilia is essential to many living systems, where the emergent metachronal waves of cilia have been hypothesized to enhance net fluid flows at low Reynolds numbers (Re). Experimental investigation of this hypothesis is critical but remains challenging. Here, we report soft miniature devices with both ciliary nonreciprocal motion and metachronal coordination and use them to investigate the quantitative relationship between metachronal coordination and the induced fluid flow. We found that only antiplectic metachronal waves with specific wave vectors could enhance fluid flows compared with the synchronized case. These findings further enable various bioinspired cilia arrays with unique functionalities of pumping and mixing viscous synthetic and biological complex fluids at low Re. Our design method and developed soft miniature devices provide unprecedented opportunities for studying ciliary biomechanics and creating cilia-inspired wireless microfluidic pumping, object manipulation and lab- and organ-on-a-chip devices, mobile microrobots, and bioengineering systems.
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    PublicationOpen Access
    Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication
    (Nature Portfolio, 2021) Yurtman, Erinç; Özer, Onur; Yüncü, Eren; Dağtaş, Nihan Dilşad; Koptekin, Dilek; Çakan, Yasin Gökhan; Özkan, Mustafa; Akbaba, Ali; Kaptan, Damla; Atağ, Gözde; Vural, Kıvılcım Başak; Gündem, Can Yümni; Martin, Louise; Kılınç, Gülşah Merve; Ghalichi, Ayshin; Açan, Sinan Can; Yaka, Reyhan; Sağlıcan, Ekin; Lagerholm, Vendela Kempe; Krzewinska, Maja; Gunther, Torsten; Miranda, Pedro Morell; Pişkin, Evangelia; Sevketoğlu, Müge; Bilgin, C. Can; Atakuman, Ciğdem; Erdal, Yılmaz Selim; Sürer, Elif; Altınışık, N. Ezgi; Lenstra, Johannes A.; Yorulmaz, Sevgi; Abazari, Mohammad Foad; Hoseinzadeh, Javad; Baird, Douglas; Bıcakcı, Erhan; Çevik, Özlem; Gerritsen, Fokke; Gotherstrom, Anders; Somel, Mehmet; Togan, İnci; Özer, Füsun; Department of Archeology and History of Art; Özbal, Rana; Faculty Member; Department of Archeology and History of Art; College of Social Sciences and Humanities; 55583
    Sheep were among the first domesticated animals, but their demographic history is little understood. Here we analyzed nuclear polymorphism and mitochondrial data (mtDNA) from ancient central and west Anatolian sheep dating from Epipaleolithic to late Neolithic, comparatively with modern-day breeds and central Asian Neolithic/Bronze Age sheep (OBI). Analyzing ancient nuclear data, we found that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds relative to Asian breeds, a conclusion supported by mtDNA haplogroup frequencies. In contrast, OBI showed higher genetic affinity to present-day Asian breeds. These results suggest that the east-west genetic structure observed in present-day breeds had already emerged by 6000 BCE, hinting at multiple sheep domestication episodes or early wild introgression in southwest Asia. Furthermore, we found that ANS are genetically distinct from all modern breeds. Our results suggest that European and Anatolian domestic sheep gene pools have been strongly remolded since the Neolithic.
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    PublicationOpen Access
    Effect of body stiffness distribution on larval fish-like efficient undulatory swimming
    (American Association for the Advancement of Science (AAAS), 2021) Wang, Tianlu; Ren, Ziyu; Hu, Wenqi; Li, Mingtong; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104
    Energy-efficient propulsion is a critical design target for robotic swimmers. Although previous studies have pointed out the importance of nonuniform body bending stiffness distribution (k) in improving the undulatory swimming efficiency of adult fish-like robots in the inertial flow regime, whether such an elastic mechanism is beneficial in the intermediate flow regime remains elusive. Hence, we develop a class of untethered soft milliswimmers consisting of a magnetic composite head and a passive elastic body with different k. These robots realize larval zebrafish-like undulatory swimming at the same scale. Investigations reveal that uniform k and high swimming frequency (60 to 100 Hz) are favorable to improve their efficiency. A shape memory polymer-based milliswimmer with tunable k on the fly confirms such findings. Such acquired knowledge can guide the design of energy-efficient leading edge-driven soft undulatory milliswimmers for future environmental and biomedical applications in the same flow regime.