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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery(Elsevier, 2020) Ekinci, Duygu; N/A; Department of Chemical and Biological Engineering; Batool, Syeda Rubab; Nazeer, Muhammad Anwaar; Kızılel, Seda; Şahin, Afsun; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological 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; 28376; 171267Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.Publication Open Access Engagement rewarded actor-critic with conservative Q-learning for speech-driven laughter backchannel generation(Association for Computing Machinery (ACM), 2021) Department of Computer Engineering; Bayramoğlu, Öykü Zeynep; Erzin, Engin; Sezgin, Tevfik Metin; Yemez, Yücel; Faculty Member; Faculty Member; Faculty Member; Department of Computer Engineering; Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); College of Engineering; Graduate School of Sciences and Engineering; N/A; 34503; 18632; 107907We propose a speech-driven laughter backchannel generation model to reward engagement during human-agent interaction. We formulate the problem as a Markov decision process where speech signal represents the state and the objective is to maximize human engagement. Since online training is often impractical in the case of human-agent interaction, we utilize the existing human-to-human dyadic interaction datasets to train our agent for the backchannel generation task. We address the problem using an actor-critic method based on conservative Q-learning (CQL), that mitigates the distributional shift problem by suppressing Q-value over-estimation during training. The proposed CQL based approach is evaluated objectively on the IEMOCAP dataset for laughter generation task. When compared to the existing off-policy Q-learning methods, we observe an improved compliance with the dataset in terms of laugh generation rate. Furthermore, we show the effectiveness of the learned policy by estimating the expected engagement using off-policy policy evaluation techniques.Publication Open Access Evolutionary multiobjective feature selection for sentiment analysis(Institute of Electrical and Electronics Engineers (IEEE), 2021) Pelin Angın; Deniz, Ayça; Department of International Relations; Angın, Merih; Faculty Member; Department of International Relations; College of Administrative Sciences and Economics; 308500Sentiment analysis is one of the prominent research areas in data mining and knowledge discovery, which has proven to be an effective technique for monitoring public opinion. The big data era with a high volume of data generated by a variety of sources has provided enhanced opportunities for utilizing sentiment analysis in various domains. In order to take best advantage of the high volume of data for accurate sentiment analysis, it is essential to clean the data before the analysis, as irrelevant or redundant data will hinder extracting valuable information. In this paper, we propose a hybrid feature selection algorithm to improve the performance of sentiment analysis tasks. Our proposed sentiment analysis approach builds a binary classification model based on two feature selection techniques: an entropy-based metric and an evolutionary algorithm. We have performed comprehensive experiments in two different domains using a benchmark dataset, Stanford Sentiment Treebank, and a real-world dataset we have created based on World Health Organization (WHO) public speeches regarding COVID-19. The proposed feature selection model is shown to achieve significant performance improvements in both datasets, increasing classification accuracy for all utilized machine learning and text representation technique combinations. Moreover, it achieves over 70% reduction in feature size, which provides efficiency in computation time and space.Publication Open Access Conditional law and occupation times of two-sided sticky Brownian motion(Elsevier, 2020) Department of Mathematics; Çağlar, Mine; Can, Buğra; Faculty Member; Department of Mathematics; College of Sciences; 105131; N/ASticky Brownian motion on the real line can be obtained as a weak solution of a system of stochastic differential equations. We find the conditional distribution of the process given the driving Brownian motion, both at an independent exponential time and at a fixed time t>0. As a classical problem, we find the distribution of the occupation times of a half-line, and at 0, which is the sticky point for the process.Publication Open Access Autophagy and cancer dormancy(Frontiers, 2021) Akçay, Arzu; Akkoç, Yunus; Peker, Nesibe; Gözüaçık, Devrim; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; 40248Metastasis and relapse account for the great majority of cancer-related deaths. Most metastatic lesions are micro metastases that have the capacity to remain in a non-dividing state called "dormancy" for months or even years. Commonly used anticancer drugs generally target actively dividing cancer cells. Therefore, cancer cells that remain in a dormant state evade conventional therapies and contribute to cancer recurrence. Cellular and molecular mechanisms of cancer dormancy are not fully understood. Recent studies indicate that a major cellular stress response mechanism, autophagy, plays an important role in the adaptation, survival and reactivation of dormant cells. In this review article, we will summarize accumulating knowledge about cellular and molecular mechanisms of cancer dormancy, and discuss the role and importance of autophagy in this context.Publication Open Access The structural basis of Akt PH domain interaction with calmodulin(Elsevier, 2021) Jang, Hyunbum; Nussinov, Ruth; N/A; Department of Chemical and Biological Engineering; Department of Computer Engineering; Weako, Jackson; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 26605; 8745Akt plays a key role in the Ras/PI3K/Akt/mTOR signaling pathway. In breast cancer, Akt translocation to the plasma membrane is enabled by the interaction of its pleckstrin homology domain (PHD) with calmodulin (CaM). At the membrane, the conformational change promoted by PIP3 releases CaM and facilitates Thr308 and Ser473 phosphorylation and activation. Here, using modeling and molecular dynamics simulations, we aim to figure out how CaM interacts with Akt's PHD at the atomic level. Our simulations show that CaM-PHD interaction is thermodynamically stable and involves a beta-strand rather than an alpha-helix, in agreement with NMR data, and that electrostatic and hydrophobic interactions are critical. The PHD interacts with CaM lobes; however, multiple modes are possible. IP4, the polar head of PIP3, weakens the CaM-PHD interaction, implicating the release mechanism at the plasma membrane. Recently, we unraveled the mechanism of PI3K alpha activation at the atomistic level and the structural basis for Ras role in the activation. Here, our atomistic structural data clarify the mechanism of how CaM interacts, delivers, and releases Akt-the next node in the Ras/PI3K pathway-at the plasma membrane.Publication Open Access Low complexity adaptation for reconfigurable intelligent surface-based MIMO systems(Institute of Electrical and Electronics Engineers (IEEE), 2020) Yiğit, Zehra; Altunbaş, İbrahim; Department of Electrical and Electronics Engineering; Başar, Ertuğrul; Faculty Member; Department of Electrical and Electronics Engineering; College of Engineering; 149116Reconfigurable intelligent surface (RIS)-based transmission technology offers a promising solution to enhance wireless communication performance cost-effectively through properly adjusting the parameters of a large number of passive reflecting elements. This letter proposes a cosine similarity theorem-based low-complexity algorithm for adapting the phase shifts of an RIS that assists a multiple-input multiple-output (MIMO) transmission system. A semi-analytical probabilistic approach is developed to derive the theoretical average bit error probability (ABEP) of the system. Furthermore, the validity of the theoretical analysis is supported through extensive computer simulations.Publication Open Access SimMBM channel simulator for media-based modulation systems(Institute of Electrical and Electronics Engineers (IEEE), 2021) Yiğit Zehra; Altunbaş, İbrahim; Department of Chemical and Biological Engineering; Başar, Ertuğrul; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 149116Media-based modulation (MBM), exploiting rich scattering properties of transmission environments via different radiation patterns of a single reconfigurable antenna (RA), has brought new insights into future communication systems. In this study, considering this innovative transmission principle, we introduce the realistic, two-dimensional (2D), and open-source SimMBM channel simulator to support various applications of MBM systems at sub-6 GHz frequency band in different environments.Publication Open Access Throughput maximization in discrete rate based full duplex wireless powered communication networks(Wiley, 2020) Şadi, Yalçın; Department of Electrical and Electronics Engineering; Ergen, Sinem Çöleri; Iqbal, Muhammad Shahid; Faculty Member; PhD Student; Department of Electrical and Electronics Engineering; College of Engineering; Graduate School of Sciences and Engineering; 7211; N/AIn this study, we consider a discrete rate full-duplex wireless powered communication network. We characterize a novel optimization framework for sum throughput maximization to determine the rate adaptation and transmission schedule subject to energy causality and user transmit power. We first formulate the problem as a mixed integer nonlinear programming problem, which is hard to solve for a global optimum in polynomial-time. Then, we investigate the characteristics of the solution and propose a polynomial time heuristic algorithm for rate adaptation and scheduling problem. Through numerical analysis, we illustrate that the proposed scheduling algorithm outperforms the conventional schemes such as equal time allocation half-duplex and on-off transmission schemes for different initial battery levels, hybrid access point transmit power and network densities.Publication Open Access A proximity mapping journey into the biology of the mammalian centrosome/cilium complex(Multidisciplinary Digital Publishing Institute (MDPI), 2020) Department of Molecular Biology and Genetics; Arslanhan, Melis Dilara; Gülensoy, Dila; Karalar, Elif Nur Fırat; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 206349The mammalian centrosome/cilium complex is composed of the centrosome, the primary cilium and the centriolar satellites, which together regulate cell polarity, signaling, proliferation and motility in cells and thereby development and homeostasis in organisms. Accordingly, deregulation of its structure and functions is implicated in various human diseases including cancer, developmental disorders and neurodegenerative diseases. To better understand these disease connections, the molecular underpinnings of the assembly, maintenance and dynamic adaptations of the centrosome/cilium complex need to be uncovered with exquisite detail. Application of proximity-based labeling methods to the centrosome/cilium complex generated spatial and temporal interaction maps for its components and provided key insights into these questions. In this review, we first describe the structure and cell cycle-linked regulation of the centrosome/cilium complex. Next, we explain the inherent biochemical and temporal limitations in probing the structure and function of the centrosome/cilium complex and describe how proximity-based labeling approaches have addressed them. Finally, we explore current insights into the knowledge we gained from the proximity mapping studies as it pertains to centrosome and cilium biogenesis and systematic characterization of the centrosome, cilium and centriolar satellite interactomes.