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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6

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    PublicationOpen 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 Engineering
    The 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.
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    PublicationOpen Access
    Shifting evaluation windows: predictable forward primes with long SOAs eliminate the impact of backward primes
    (Public Library of Science, 2013) Fockenberg, Daniel A.; Koole, Sander L.; Lakens, Daniël; Department of Psychology; Semin, Gün Refik; Researcher; Department of Psychology; College of Social Sciences and Humanities; 58066
    Recent work suggests that people evaluate target stimuli within short and flexible time periods called evaluation windows. Stimuli that briefly precede a target (forward primes) or briefly succeed a target (backward primes) are often included in the target's evaluation. In this article, the authors propose that predictable forward primes act as ""go"" signals that prepare target processing, such that earlier forward primes pull the evaluation windows forward in time. Earlier forward primes may thus reduce the impact of backward primes. This shifting evaluation windows hypothesis was tested in two experiments using an evaluative decision task with predictable (vs. unpredictable) forward and backward primes. As expected, a longer time interval between a predictable forward prime and a target eliminated backward priming. In contrast, the time interval between an unpredictable forward primes and a target had no effects on backward priming. These findings suggest that predictable features of dynamic stimuli can shape target extraction by determining which information is included (or excluded) in rapid evaluation processes.
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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
    Dynamic transcriptional response of Saccharomyces cerevisiae cells to copper
    (Nature Publishing Group (NPG), 2020) Öç, Şebnem; Kırdar, Betül; Eraslan, Serpil; Other; Koç University Hospital
    Copper 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.
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    PublicationOpen 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 Sciences
    Prokaryotes 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.
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    PublicationOpen Access
    On the physical design of molecular communication receiver based on nanoscale biosensors
    (Institute of Electrical and Electronics Engineers (IEEE), 2016) Department of Electrical and Electronics Engineering; Kuşcu, Murat; Akan, Özgür Barış; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering
    Molecular communications, where molecules are used to encode, transmit, and receive information, are a promising means of enabling the coordination of nanoscale devices. The paradigm has been extensively studied from various aspects, including channel modeling and noise analysis. Comparatively little attention has been given to the physical design of molecular receiver and transmitter, envisioning biological synthetic cells with intrinsic molecular reception and transmission capabilities as the future nanomachines. However, this assumption leads to a discrepancy between the envisaged applications requiring complex communication interfaces and protocols, and the very limited computational capacities of the envisioned biological nanomachines. In this paper, we examine the feasibility of designing a molecular receiver, in a physical domain other than synthetic biology, meeting the basic requirements of nanonetwork applications. We first review the state-of-the-art biosensing approaches to determine whether they can inspire a receiver design. We reveal that the nanoscale field effect transistor-based electrical biosensor technology (bioFET) is particularly a useful starting point for designing a molecular receiver. Focusing on bioFET-based molecular receivers with a conceptual approach, we provide a guideline elaborating on their operation principles, performance metrics, and design parameters. We then provide a simple model for signal flow in silicon nanowire FET-based molecular receiver. Finally, we discuss the practical challenges of implementing the receiver and present the future research avenues from a communication theoretical perspective.
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    PublicationOpen 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 Engineering
    Molecular 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.
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    PublicationOpen 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; 1674
    We 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.
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    PublicationOpen 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 Engineering
    Nanonetworks 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.
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    PublicationOpen 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.