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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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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 PathoNet introduced as a deep neural network backend for evaluation of Ki-67 and tumor-infiltrating lymphocytes in breast cancer(Nature Publishing Group (NPG), 2021) Sabzi, R.; Pakniyat Jahromi, B.; Firouzabadi, D.; Movahedi, F.; Kohandel Shirazi, M.; Majidi, S.; Dehghanian, A.; N/A; Faculty Member; Graduate School of Sciences and EngineeringThe nuclear protein Ki-67 and Tumor infiltrating lymphocytes (TILs) have been introduced as prognostic factors in predicting both tumor progression and probable response to chemotherapy. The value of Ki-67 index and TILs in approach to heterogeneous tumors such as Breast cancer (BC) that is the most common cancer in women worldwide, has been highlighted in literature. Considering that estimation of both factors are dependent on professional pathologists’ observation and inter-individual variations may also exist, automated methods using machine learning, specifically approaches based on deep learning, have attracted attention. Yet, deep learning methods need considerable annotated data. In the absence of publicly available benchmarks for BC Ki-67 cell detection and further annotated classification of cells, In this study we propose SHIDC-BC-Ki-67 as a dataset for the aforementioned purpose. We also introduce a novel pipeline and backend, for estimation of Ki-67 expression and simultaneous determination of intratumoral TILs score in breast cancer cells. Further, we show that despite the challenges that our proposed model has encountered, our proposed backend, PathoNet, outperforms the state of the art methods proposed to date with regard to harmonic mean measure acquired. Dataset is publicly available in https://shiraz-hidc.com and all experiment codes are published in https://github.com/SHIDCenter/PathoNet.Publication Open 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; 316349Bio-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.Publication Open Access Dynamic transcriptional response of Saccharomyces cerevisiae cells to copper(Nature Publishing Group (NPG), 2020) Öç, Şebnem; Kırdar, Betül; Eraslan, Serpil; Other; Koç University HospitalCopper is a crucial trace element for all living systems and any deficiency in copper homeostasis leads to the development of severe diseases in humans. The observation of extensive evolutionary conservation in copper homeostatic systems between human and Saccharomyces cerevisiae made this organism a suitable model organism for elucidating molecular mechanisms of copper transport and homeostasis. In this study, the dynamic transcriptional response of both the reference strain and homozygous deletion mutant strain of CCC2, which encodes a Cu2+-transporting P-type ATPase, were investigated following the introduction of copper impulse to reach a copper concentration which was shown to improve the respiration capacity of CCC2 deletion mutants. The analysis of data by using different clustering algorithms revealed significantly affected processes and pathways in response to a switch from copper deficient environment to elevated copper levels. Sulfur compound, methionine and cysteine biosynthetic processes were identified as significantly affected processes for the first time in this study. Stress response, cellular response to DNA damage, iron ion homeostasis, ubiquitin dependent proteolysis, autophagy and regulation of macroautophagy, DNA repair and replication, as well as organization of mitochondrial respiratory chain complex IV, mitochondrial organization and translation were identified as significantly affected processes in only CCC2 deleted strain. The integration of the transcriptomic data with regulome revealed the differences in the extensive re-wiring of dynamic transcriptional organization and regulation in these strains.Publication Open Access Epithelial Wnt secretion drives the progression of inflammation-induced colon carcinoma in murine model(Cell Press, 2021) Değirmenci, Bahar; Dinçer, Cansu; Demirel, Habibe Cansu; Berkova, Linda; Moor, Andreas E.; Kahraman, Abdullah; Hausmann, George; Aguet, Michel; Valenta, Tomas; Basler, Konrad; Department of Chemical and Biological Engineering; Tunçbağ, Nurcan; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 245513Colon cancer is initiated by stem cells that escape the strict control. This process is often driven through aberrant activation of Wnt signaling by mutations in components acting downstream of the receptor complex that unfetter tumor cells from the need for Wnts. Here we describe a class of colon cancer that does not depend on mutated core components of the Wnt pathway. Genetically blocking Wnt secretion from epithelial cells of such tumors results in apoptosis, reduced expression of colon cancer markers, followed by enhanced tumor differentiation. In contrast to the normal colonic epithelium, such tumor cells autosecrete Wnts to maintain their uncontrolled proliferative behavior. In humans, we determined certain cases of colon cancers in which the Wnt pathway is hyperactive, but not through mutations in its core components. Our findings illuminate the path in therapy to find further subtypes of Wnt-dependent colon cancer that might be to Wnt secretion inhibitors.Publication Open Access Few-qubit quantum refrigerator for cooling a multi-qubit system(Nature Publishing Group (NPG), 2021) Arısoy, Onat; Department of Physics; Müstecaplıoğlu, Özgür Esat; Faculty Member; Department of Physics; College of Sciences; 1674We propose to use a few-qubit system as a compact quantum refrigerator for cooling an interacting multi-qubit system. We specifically consider a central qubit coupled to N ancilla qubits in a so-called spin-star model to be used as refrigerant by means of short interactions with a many-qubit system to be cooled. We first show that if the interaction between the qubits is of the longitudinal and ferromagnetic Ising model form, the central qubit is colder than the environment. We summarize how preparing the refrigerant qubits using the spin-star model paves the way for the cooling of a many-qubit system by means of a collisional route to thermalization. We discuss a simple refrigeration cycle, considering the operation cost and cooling efficiency, which can be controlled by N and the qubit–qubit interaction strength. Besides, bounds on the achievable temperature are established. Such few-qubit compact quantum refrigerators can be significant to reduce dimensions of quantum technology applications, can be easy to integrate into all-qubit systems, and can increase the speed and power of quantum computing and thermal devices.Publication Open Access Exciton recycling via InP quantum dot funnels for luminescent solar concentrators(Tsinghua University, 2021) Ow-Yang, Cleva W.; N/A; N/A; Department of Physics; Department of Electrical and Electronics Engineering; Jalali, Houman Bahmani; Sadeghi, Sadra; Toker, Işınsu Baylam; Han, Mertcan; Sennaroğlu, Alphan; Nizamoğlu, Sedat; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Physics; Department of Electrical and Electronics Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; N/A; 23851; 130295Luminescent solar concentrators (LSC) absorb large-area solar radiation and guide down-converted emission to solar cells for electricity production. Quantum dots (QDs) have been widely engineered at device and quantum dot levels for LSCs. Here, we demonstrate cascaded energy transfer and exciton recycling at nanoassembly level for LSCs. The graded structure composed of different sized toxic-heavy-metal-free InP/ZnS core/shell QDs incorporated on copper doped InP QDs, facilitating exciton routing toward narrow band gap QDs at a high nonradiative energy transfer efficiency of 66%. At the final stage of non-radiative energy transfer, the photogenerated holes make ultrafast electronic transitions to copper-induced mid-gap states for radiative recombination in the near-infrared. The exciton recycling facilitates a photoluminescence quantum yield increase of 34% and 61% in comparison with semi-graded and ungraded energy profiles, respectively. Thanks to the suppressed reabsorption and enhanced photoluminescence quantum yield, the graded LSC achieved an optical quantum efficiency of 22.2%. Hence, engineering at nanoassembly level combined with nonradiative energy transfer and exciton funneling offer promise for efficient solar energy harvesting.Publication Open Access Wireless MRI-powered reversible orientation-locking capsule robot(Wiley, 2021) Erin, Önder; Boyvat, Mustafa; Lazovic, Jelena; Tiryaki, Mehmet Efe; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104Magnetic resonance imaging (MRI) scanners do not provide only high-resolution medical imaging but also magnetic robot actuation and tracking. However, the rotational motion capabilities of MRI-powered wireless magnetic capsule-type robots have been limited due to the very high axial magnetic field inside the MRI scanner. Medical functionalities of such robots also remain a challenge due to the miniature robot designs. Therefore, a wireless capsule-type reversible orientation-locking robot (REVOLBOT) is proposed that has decoupled translational motion and planar orientation change capability by locking and unlocking the rotation of a spherical ferrous bead inside the robot on demand. Such an on-demand locking/unlocking mechanism is achieved by a phase-changing wax material in which the ferrous bead is embedded inside. Controlled and on-demand hyperthermia and drug delivery using wireless power transfer-based Joule heating induced by external alternating magnetic fields are the additional features of this robot. The experimental feasibility of the REVOLBOT prototype with steerable navigation, medical function, and MRI tracking capabilities with an 1.33 Hz scan rate is demonstrated inside a preclinical 7T small-animal MRI scanner. The proposed robot has the potential for future clinical use in teleoperated minimally invasive treatment procedures with hyperthermia and drug delivery capabilities while being wirelessly powered and monitored inside MRI scanners.nd. Such an on-demand locking/unlocking mechanism is achieved by a phase-changing wax material in which the ferrous bead is embedded inside. Controlled and on-demand hyperthermia and drug delivery using wireless power transfer-based Joule heating induced by external alternating magnetic fields are the additional features of this robot. The experimental feasibility of the REVOLBOT prototype with steerable navigation, medical function, and MRI tracking capabilities with an 1.33 Hz scan rate is demonstrated inside a preclinical 7T small-animal MRI scanner. The proposed robot has the potential for future clinical use in teleoperated minimally invasive treatment procedures with hyperthermia and drug delivery capabilities while being wirelessly powered and monitored inside MRI scanners.Publication Open Access Estimation of pulsatile energy dissipation in intersecting pipe junctions using inflow pulsatility indices(American Institute of Physics (AIP) Publishing, 2021) Dur, Onur; Department of Mechanical Engineering; Pekkan, Kerem; Rasooli, Reza; Faculty Member; Researcher; Department of Mechanical Engineering; Graduate School of Health Sciences; College of Engineering; 161845; N/AThis study aims to characterize the effect of inflow pulsatility on the hydrodynamic power loss inside intersecting double-inlet, double-outlet pipe intersection (DIPI) with cross-flow mixing. An extensive set of computational fluid dynamics (CFD) simulations was performed in order to identify the individual effects of flow pulsatility parameters, i.e., amplitude, frequency, and relative phase shift between the inflow waveform oscillations, on power loss. An experimentally validated second order accurate solver is employed in this study. To predict the pulsatile flow performance of any given arbitrary inflow waveforms, we proposed three easy-to-calculate pulsatility indices. The frequency-coupled quasi-steady flow theory is incorporated to identify the functional form of pulsatile power loss as a function of these indices. Our results indicated that the power loss within the inflow branch sections, lumped outflow-junction section, and the whole conduit correlates strongly with the pulsatility of each inflow waveform, the total inflow pulsatility, and inflow frequency content, respectively. The complete CFD simulation matrix provided a unified analytical expression that predicts pulsatile power loss inside a one-degree offset DIPI geometry. The predictive accuracy of this expression is evaluated in comparison to the CFD evaluation of arbitrary multi-harmonic inflow waveforms. These results have important implications on hydrodynamic pipe networks that employ complex junctions as well as in the patient-to-patient comparison of surgically created vascular connections. Coupling the present analytical pulsatile power loss expression with non-dimensional steady power loss formulation provided a valuable predictive tool to estimate the pulsatile energy dissipation for any arbitrary junction geometry with minimum use of the costly CFD computations.Publication Open Access Human mobility at Tell Atchana (Alalakh), Hatay, Turkey during the 2nd millennium BC: integration of isotopic and genomic evidence(Public Library of Science, 2021) Eisenmann, S.; Skourtanioti, E.; Akar, M.; Ilgner, J.; Gnecchi Ruscone, G. A.; le Roux, P.; Shafiq, R.; Neumann, G. U.; Keller, M.; Freund, C.; Marzo, S.; Lucas, M.; Krause, J.; Roberts, P.; Yener, K. A.; Stockhammer, P. W.; Ingman, Tara; Researcher; Koç University Research Center for Anatolian Civilizations (ANAMED) / Anadolu Medeniyetleri Araştırma Merkezi (ANAMED)The Middle and Late Bronze Age, a period roughly spanning the 2(nd) millennium BC (ca. 2000-1200 BC) in the Near East, is frequently referred to as the first 'international age', characterized by intense and far-reaching contacts between different entities from the eastern Mediterranean to the Near East and beyond. In a large-scale tandem study of stable isotopes and ancient DNA of individuals excavated at Tell Atchana (Alalakh, located in Hatay, Turkey), we explored the role of mobility at the capital of a regional kingdom, named Mukish during the Late Bronze Age, which spanned the Amuq Valley and some areas beyond. We generated strontium and oxygen isotope data from dental enamel for 53 individuals and 77 individuals, respectively, and added ancient DNA data of 10 newly sequenced individuals to a dataset of 27 individuals published in 2020. Additionally, we improved the DNA coverage of one individual from this 2020 dataset. The DNA data revealed a very homogeneous gene pool. This picture of an overwhelmingly local ancestry was consistent with the evidence of local upbringing in most of the individuals indicated by the isotopic data, where only five were found to be non-local. High levels of contact, trade, and exchange of ideas and goods in the Middle and Late Bronze Ages, therefore, seem not to have translated into high levels of individual mobility detectable at Tell Atchana.