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Publication Open Access 3D printed personalized magnetic micromachines from patient blood-derived biomaterials(American Association for the Advancement of Science (AAAS), 2021) Ceylan, Hakan; Doğan, Nihal Olcay; Yaşa, İmmihan Ceren; Department of Mechanical Engineering; Sitti, Metin; Musaoğlu, Miraç Nur; Kulalı, Zeynep Umut; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104; N/A; N/AWhile recent wireless micromachines have shown increasing potential for medical use, their potential safety risks concerning biocompatibility need to be mitigated. They are typically constructed from materials that are not intrinsically compatible with physiological environments. Here, we propose a personalized approach by using patient blood-derivable biomaterials as the main construction fabric of wireless medical micromachines to alleviate safety risks from biocompatibility. We demonstrate 3D printed multiresponsive microswimmers and microrollers made from magnetic nanocomposites of blood plasma, serum albumin protein, and platelet lysate. These micro-machines respond to time-variant magnetic fields for torque-driven steerable motion and exhibit multiple cycles of pH-responsive two-way shape memory behavior for controlled cargo delivery and release applications. Their proteinaceous fabrics enable enzymatic degradability with proteinases, thereby lowering risks of long-term toxicity. The personalized micromachine fabrication strategy we conceptualize here can affect various future medical robots and devices made of autologous biomaterials to improve biocompatibility and smart functionality.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 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 All optical control of magnetization in quantum confined ultrathin magnetic metals(Nature Publishing Group (NPG), 2021) Department of Physics; Department of Electrical and Electronics Engineering; N/A; Müstecaplıoğlu, Özgür Esat; Onbaşlı, Mehmet Cengiz; Naseem, Muhammad Tahir; Zanjani, Saeedeh Mokarian; Faculty Member; Faculty Member; Department of Physics; Department of Electrical and Electronics Engineering; College of Sciences; College of Engineering; Graduate School of Sciences and Engineering; 1674; 258783; N/A; N/AAll-optical control dynamics of magnetization in sub-10 nm metallic thin films are investigated, as these films with quantum confinement undergo unique interactions with femtosecond laser pulses. Our theoretical analysis based on the free electron model shows that the density of states at Fermi level (DOSF) and electron-phonon coupling coefficients (G(ep)) in ultrathin metals have very high sensitivity to film thickness within a few angstroms. We show that completely different magnetization dynamics characteristics emerge if DOSF and G(ep) depend on thickness compared with bulk metals. Our model suggests highly efficient energy transfer from femtosecond laser photons to spin waves due to minimal energy absorption by phonons. This sensitivity to the thickness and efficient energy transfer offers an opportunity to obtain ultrafast on-chip magnetization dynamics.Publication Open Access An information theoretical analysis of human insulin-glucose system toward the internet of bio-nano things(Institute of Electrical and Electronics Engineers (IEEE), 2017) Department of Electrical and Electronics Engineering; Abbasi, Naveed Ahmed; Akan, Özgür Barış; Faculty Member; Department of Electrical and Electronics Engineering; Graduate School of Sciences and EngineeringMolecular communication is an important tool to understand biological communications with many promising applications in Internet of Bio-Nano Things (IoBNT). The insulin-glucose system is of key significance among the major intra-body nanonetworks, since it fulfills metabolic requirements of the body. The study of biological networks from information and communication theoretical (ICT) perspective is necessary for their introduction in the IoBNT framework. Therefore, the objective of this paper is to provide and analyze for the first time in the literature, a simple molecular communication model of the human insulin-glucose system from ICT perspective. The data rate, channel capacity, and the group propagation delay are analyzed for a two-cell network between a pancreatic beta cell and a muscle cell that are connected through a capillary. The results point out a correlation between an increase in insulin resistance and a decrease in the data rate and channel capacity, an increase in the insulin transmission rate, and an increase in the propagation delay. We also propose applications for the introduction of the system in the IoBNT framework. Multi-cell insulin glucose system models may be based on this simple model to help in the investigation, diagnosis, and treatment of insulin resistance by means of novel IoBNT applications.Publication Open Access An integrated computational-experimental hierarchical approach for the rational design of an IL/UiO-66 composite offering infinite CO2 selectivity(Wiley, 2022) Department of Chemical and Biological Engineering; Department of Chemistry; Zeeshan, Muhammad; Gülbalkan, Hasan Can; Durak, Özce; Haşlak, Zeynep Pınar; Ünal, Uğur; Keskin, Seda; Uzun, Alper; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Department of Chemistry; 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); College of Engineering; College of Sciences; Graduate School of Sciences and Engineering; N/A; N/A; N/A; N/A; 42079; 40548; 59917Owing to the possibility of generating theoretically unlimited numbers of ionic liquid (IL)-metal-organic framework (MOF) combinations, experimental studies on IL/MOF composites for gas separation applications are mostly conducted on a trial-and-error basis. To address this problem, an integrated computational-experimental hierarchical approach is presented for selecting the best IL-MOF combination for a target gas separation application. For this purpose, UiO-66 and pyrrolidinium-based ILs are chosen as the parent MOF and IL family, respectively, and three powerful computational tools, Conductor-like Screening Model for Realistic Solvents calculations, density functional theory calculations, and grand canonical Monte Carlo simulations, are integrated to identify the most promising IL-UiO-66 combination as 1-n-butyl-1-methylpyrrolidinium dicyanamide/UiO-66, [BMPyrr][DCA]/UiO-66. Then, this composite is synthesized, characterized in deep detail, and tested for CO2/N-2, CO2/CH4, and CH4/N-2 separations. Results demonstrate that [BMPyrr][DCA]/UiO-66 offers an extraordinary gas separation performance, with practically infinite CO2 and CH4 selectivities over N-2 at 15 degrees C and at low pressures. The integrated hierarchical approach proposed in this work paves the way for the rational design and development of novel IL/MOF composites offering exceptional performance for any desired gas separation application.Publication Open 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; 55583Sheep 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.Publication Open 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.Publication Open Access Asymmetry in mechanosensitive gene expression during aortic arch morphogenesis(Nature Publishing Group (NPG), 2018) Kowalski, William J.; Keller, Bradley B.; Department of Mechanical Engineering; Pekkan, Kerem; Karakaya, Cansu; Göktaş, Selda; Çelik, Merve; Faculty Member; Master Student; Researcher; Undergraduate Student; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; 161845; N/A; N/A; N/AEmbryonic aortic arches (AA) are initially bilaterally paired, transitional vessels and failures in remodeling based on hemodynamic and growth-related adaptations cause a spectrum of congenital heart disease (CHD) anatomies. Identifying regulatory mechanisms and cross-talk between the genetic elements of these vessels are critical to understand the ethiology of CHD and refine predictive computational models. This study aims to screen expression profiles of fundamental biological pathways in AA at early stages of chick embryo morphogenesis and correlate them with our current understanding of growth and mechanical loading. Reverse transcription-quantitative PCR (RT-qPCR) was followed by correlation and novel peak expression analyses to compare the behaviour and activation period of the genes. Available protein networks were also integrated to investigate the interactions between molecules and highlight major hierarchies. Only wall shear stress (WSS) and growth-correlated expression patterns were investigated. Effect of WSS was seen directly on angiogenesis as well on structural and apoptosis-related genes. Our time-resolved network suggested that WSS-correlated genes coordinate the activity of critical growth factors. Moreover, differential gene expression of left and right AA might be an indicator of subsequent asymmetric morphogenesis. These findings may further our understanding of the complex processes of cardiac morphogenesis and errors resulting in CHD.