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Publication Metadata only Adaptive tracking algorithm for trajectory analysis of cells and layer-by-layer assessment of motility dynamics(Pergamon-Elsevier Science Ltd, 2022) Bayraktar, Halil; N/A; Department of Molecular Biology and Genetics; Qureshi, Mohammad Haroon; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; Graduate School of Sciences and Engineering; College of Sciences; N/A; 105301Tracking biological objects such as cells or subcellular components imaged with time-lapse microscopy enables us to understand the molecular principles about the dynamics of cell behaviors. However, automatic object detection, segmentation and extracting trajectories remain as a rate-limiting step due to intrinsic challenges of video processing. This paper presents an adaptive tracking algorithm (Adtari) that automatically finds the op-timum search radius and cell linkages to determine trajectories in consecutive frames. A critical assumption in most tracking studies is that displacement remains unchanged throughout the movie and cells in a few frames are usually analyzed to determine its magnitude. Tracking errors and inaccurate association of cells may occur if the user does not correctly evaluate the value or prior knowledge is not present on cell movement. The key novelty of our method is that minimum intercellular distance and maximum displacement of cells between frames are dynamically computed and used to determine the threshold distance. Since the space between cells is highly variable in a given frame, our software recursively alters the magnitude to determine all plausible matches in the trajectory analysis. Our method therefore eliminates a major preprocessing step where a constant distance was used to determine the neighbor cells in tracking methods. Cells having multiple overlaps and splitting events were further evaluated by using the shape attributes including perimeter, area, ellipticity and distance. The features were applied to determine the closest matches by minimizing the difference in their magnitudes. Finally, reporting section of our software were used to generate instant maps by overlaying cell features and trajectories. Adtari was validated by using videos with variable signal-to-noise, contrast ratio and cell density. We compared the adaptive tracking with constant distance and other methods to evaluate performance and its efficiency. Our algorithm yields reduced mismatch ratio, increased ratio of whole cell track, higher frame tracking efficiency and allows layer-by-layer assessment of motility to characterize single-cells. Adaptive tracking provides a reliable, accurate, time efficient and user-friendly open source software that is well suited for analysis of 2D fluorescence microscopy video datasets.Publication Metadata only Encapsulation of pancreatic islets within nano-thin functional polyethylene glycol coatings for enhanced insulin secretion(Mary Ann Liebert, Inc, 2010) Scavone, Andrew; Liu, Xiang; Nothias, Jean-Manuel; Ostrega, Diane; WitkoWSKi, Piotr; Millis, Michael; Department of Chemical and Biological Engineering; Kızılel, Seda; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 28376Covalent attachment of polymers to cells and tissues could be used to solve a variety of problems associated with cellular therapies. Insulin-dependent diabetes mellitus is a disease resulting from the autoimmune destruction of the beta cells of the islets of Langerhans in the pancreas. Transplantation of islets into diabetic patients is an attractive form of treatment, provided that the islets could be protected from the host's immune system to prevent graft rejection, and smaller numbers of islets transplanted in smaller volumes could be sufficient to reverse diabetes. Therefore, a need exists to develop islet encapsulation strategies that minimize transplant volume. In this study, we demonstrate the formation of nano-thin, poly(ethylene glycol) (PEG)-rich functional conformal coatings on individual islets via layer-by-layer assembly technique. The surface of the islets is modified with biotin-PEG-N-hydroxysuccinimide (NHS), and the islets are further covered by streptavidin (SA) and biotin-PEG-peptide conjugates using the layer-by-layer method. An insulinotropic ligand, glucagon-like peptide-1 (GLP-1), is conjugated to biotin-PEG-NHS. The insulinotropic effect of GLP-1 is investigated through layer-by-layer encapsulation of islets using the biotin-PEG-GLP-1 conjugate. The effect of islet surface modification using the biotin-PEG-GLP-1 conjugate on insulin secretion in response to glucose challenge is compared via static incubation and dynamic perifusion assays. The results show that islets coated with the functional PEG conjugate are capable of secreting more insulin in response to high glucose levels compared to control islets. Finally, the presence of SA is confirmed by indirect fluorescent staining with SA-Cy3, and the presence of PEG-peptide on the surface of the islets after treatment with biotin-PEG-GLP-1 is confirmed by indirect fluorescent staining with biotin-PEG-fluorescein isothiocyanate (FITC) and separately with an anti-GLP-1 antibody. This work demonstrates the feasibility of treating pancreatic islets with reactive polymeric segments and provides the foundation for a novel means of potential immunoisolation. With this technique, it may be possible to encapsulate and/or modify islets before portal vein transplantation and reduce transplantation volume significantly, and promote islet viability and insulin secretion due to the presence of insulinotropic peptides on the islet surface. Layer-by-layer self-assembly of PEG-GLP-1 offers a unique approach to islet encapsulation to stimulate insulin secretion in response to high glucose levels.Publication Metadata only Immune cell-based microrobots for remote magnetic actuation, antitumor activity, and medical imaging(Wiley, 2024) Dogan, Nihal Olcay; Suadiye, Eyluel; Wrede, Paul; Lazovic, Jelena; Dayan, Cem Balda; Soon, Ren Hao; Aghakhani, Amirreza; Richter, Gunther; Department of Mechanical Engineering; Sitti, Metin; Department of Mechanical Engineering; College of Engineering; School of MedicineTranslating medical microrobots into clinics requires tracking, localization, and performing assigned medical tasks at target locations, which can only happen when appropriate design, actuation mechanisms, and medical imaging systems are integrated into a single microrobot. Despite this, these parameters are not fully considered when designing macrophage-based microrobots. This study presents living macrophage-based microrobots that combine macrophages with magnetic Janus particles coated with FePt nanofilm for magnetic steering and medical imaging and bacterial lipopolysaccharides for stimulating macrophages in a tumor-killing state. The macrophage-based microrobots combine wireless magnetic actuation, tracking with medical imaging techniques, and antitumor abilities. These microrobots are imaged under magnetic resonance imaging and optoacoustic imaging in soft-tissue-mimicking phantoms and ex vivo conditions. Magnetic actuation and real-time imaging of microrobots are demonstrated under static and physiologically relevant flow conditions using optoacoustic imaging. Further, macrophage-based microrobots are magnetically steered toward urinary bladder tumor spheroids and imaged with a handheld optoacoustic device, where the microrobots significantly reduce the viability of tumor spheroids. The proposed approach demonstrates the proof-of-concept feasibility of integrating macrophage-based microrobots into clinic imaging modalities for cancer targeting and intervention, and can also be implemented for various other medical applications. Live macrophage-based microrobots integrate magnetic actuation, tracking, and targeted cancer treatment within a single microrobot system. Magnetic resonance and optoacoustic medical imaging of such microrobot swarms are demonstrated. Optoacoustic imaging-guided real-time magnetic actuation of macrophage-based microrobots is performed ex vivo and in vitro. Developing immune cell-based therapies based on this biohybrid design may pave the way for future medical applications.Publication Metadata only In vitro blastocyst implantation model by the use of synthetic polymer foam scaffolds(Mary Ann Liebert, Inc, 2022) Başöz, Deniz; Yücel, Deniz; N/A; Ergün, Yağmur; Kocabay, Ahmet; Taşkın, Ali Cihan; Karahüseyinoğlu, Serçin; Master Student; Other; Other; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; N/A; N/A; School of Medicine; N/A; N/A; 291296; 110772N/APublication Metadata only Integrating molecular simulations with machine learning guides in the design and synthesis of [bmim][bf(4)]/mof composites for co(2)/n(2) separation(American Chemical Society, 2023) N/A; N/A; N/A; N/A; Department of Chemical and Biological Engineering; Department of Chemical and Biological Engineering; Harman, Hilal Dağlar; Gülbalkan, Hasan Can; Habib, Nitasha; Durak, Özce; Uzun, Alper; Keskin, Seda; PhD Student; PhD Student; PhD Student; Undergraduate Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; 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); Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences; College of Engineering and Engineering; College of Engineering; N/A; N/A; N/A; N/A; 59917; 40548Considering the existence of a large number and variety of metal-organic frameworks (MOFs) and ionic liquids (ILs), assessing the gas separation potential of all possible IL/MOF composites by purely experimental methods is not practical. In this work, we combined molecular simulations and machine learning (ML) algorithms to computationally design an IL/MOF composite. Molecular simulations were first performed to screen approximately 1000 different composites of 1-n-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) with a large variety of MOFs for CO2 and N2 adsorption. The results of simulations were used to develop ML models that can accurately predict the adsorption and separation performances of [BMIM][BF4]/MOF composites. The most important features that affect the CO2/N2 selectivity of composites were extracted from ML and utilized to computationally generate an IL/MOF composite, [BMIM][BF4]/UiO-66, which was not present in the original material data set. This composite was finally synthesized, characterized, and tested for CO2/N2 separation. Experimentally measured CO2/N2 selectivity of the [BMIM][BF4]/UiO-66 composite matched well with the selectivity predicted by the ML model, and it was found to be comparable, if not higher than that of all previously synthesized [BMIM][BF4]/MOF composites reported in the literature. Our proposed approach of combining molecular simulations with ML models will be highly useful to accurately predict the CO2/N2 separation performances of any [BMIM][BF4]/MOF composite within seconds compared to the extensive time and effort requirements of purely experimental methods.Publication Metadata only Mustgan: multi-stream generative adversarial networks for MR image synthesis(Elsevier, 2021) Yurt, Mahmut; Dar, Salman U. H.; Oguz, Kader K.; Cukur, Tolga; Erdem, Erkut; Department of Computer Engineering; Erdem, Aykut; Faculty Member; Department of Computer Engineering; College of Engineering; 20331Multi-contrast MRI protocols increase the level of morphological information available for diagnosis. Yet, the number and quality of contrasts are limited in practice by various factors including scan time and patient motion. Synthesis of missing or corrupted contrasts from other high-quality ones can alleviate this limitation. When a single target contrast is of interest, common approaches for multi-contrast MRI involve either one-to-one or many-to-one synthesis methods depending on their input. One-to-one methods take as input a single source contrast, and they learn a latent representation sensitive to unique features of the source. Meanwhile, many-to-one methods receive multiple distinct sources, and they learn a shared latent representation more sensitive to common features across sources. For enhanced image synthesis, we propose a multi-stream approach that aggregates information across multiple source images via a mixture of multiple one-to-one streams and a joint many-to-one stream. The complementary feature maps generated in the one-to-one streams and the shared feature maps generated in the many to-one stream are combined with a fusion block. The location of the fusion block is adaptively modified to maximize task-specific performance. Quantitative and radiological assessments on T-1,- T-2-, PD-weighted, and FLAIR images clearly demonstrate the superior performance of the proposed method compared to previous state-of-the-art one-to-one and many-to-one methods. (C) 2020 Elsevier B.V. All rights reserved.Publication Metadata only Quantization and analysis of hippocampal morphometric changes due to dementia of alzheimer type using metric distances based on large deformation diffeomorphic metric mapping(Elsevier, 2011) Beg, Mirza Faisal; Ceritoglu, Can; Wang, Lei; Morris, John C.; Csernansky, John G.; Miller, Michael I.; Ratnanather, J. Tilak; Department of Mathematics; Ceyhan, Elvan; Faculty Member; Department of Mathematics; College of Sciences; N/AThe metric distance obtained from the large deformation diffeomorphic metric mapping (LDDMM) algorithm is used to quantize changes in morphometry of brain structures due to neuropsychiatric diseases. For illustrative purposes we consider changes in hippocampal morphometry (shape and size) due to very mild dementia of the Alzheimer type (DAT). LDDMM, which was previously used to calculate dense one-to-one correspondence vector fields between hippocampal shapes, measures the morphometric differences with respect to a template hippocampus by assigning metric distances on the space of anatomical images thereby allowing for direct comparison of morphometric differences. We characterize what information the metric distances provide in terms of size and shape given the hippocampal, brain and intracranial volumes. We demonstrate that metric distance is a measure of morphometry (i.e., shape and size) but mostly a measure of shape, while volume is mostly a measure of size. Moreover, we show how metric distances can be used in cross-sectional, longitudinal analysis, as well as left-right asymmetry comparisons, and provide how the metric distances can serve as a discriminative tool using logistic regression. Thus, we show that metric distances with respect to a template computed via LDDMM can be a powerful tool in detecting differences in shape. (C) 2011 Elsevier Ltd. All rights reserved.Publication Metadata only Recent advances in the design of implantable insulin secreting heterocellular islet organoids(Elsevier Sci Ltd, 2021) Sousa, Ana Rita; Oliveira, Mariana B.; Mano, Joao F.; N/A; N/A; N/A; Department of Chemical and Biological Engineering; Akolpoğlu, Mükrime Birgül; İnceoğlu, Yasemin; Bozüyük, Uğur; Kızılel, Seda; Master Student; Master Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; N/A; 28376Islet transplantation has proved one of the most remarkable transmissions from an experimental curiosity into a routine clinical application for the treatment of type I diabetes (T1D). Current efforts for taking this technology one-step further are now focusing on overcoming islet donor shortage, engraftment, prolonged islet availability, post-transplant vascularization, and coming up with new strategies to eliminate lifelong immunosuppression. To this end, insulin secreting 3D cell clusters composed of different types of cells, also referred as heterocellular islet organoids, spheroids, or pseudoislets, have been engineered to overcome the challenges encountered by the current islet transplantation protocols. beta-cells or native islets are accompanied by helper cells, also referred to as accessory cells, to generate a cell cluster that is not only able to accurately secrete insulin in response to glucose, but also superior in terms of other key features (e.g. maintaining a vasculature, longer durability in vivo and not necessitating immunosuppression after transplantation). Over the past decade, numerous 3D cell culture techniques have been integrated to create an engineered heterocellular islet organoid that addresses current obstacles. Here, we first discuss the different cell types used to prepare heterocellular organoids for islet transplantation and their contribution to the organoids design. We then introduce various cell culture techniques that are incorporated to prepare a fully functional and insulin secreting organoids with select features. Finally, we discuss the challenges and present a future outlook for improving clinical outcomes of islet transplantation.Publication Metadata only Ruthenium-induced corneal collagen crosslinking under visible light(Elsevier, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; Department of Mechanical Engineering; N/A; Department of Chemical and Biological Engineering; Gülzar, Ayesha; Yıldız, Erdost; Kaleli, Humeyra Nur; Nazeer, Muhammad Anwaar; Zibandeh, Noushin; Malik, Anjum Naeem; Taş, Ayşe Yıldız; Lazoğlu, İsmail; Şahin, Afsun; Kızılel, Seda; PhD Student; PhD Student; PhD Student; PhD Student; Researcher; PhD Student; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Department of Mechanical Engineering; 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; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; Graduate School of Sciences and Engineering; N/A; Graduate School of Sciences and Engineering; School of Medicine; College of Engineering; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; N/A; N/A; 200905; 179391; 171267; 28376Corneal collagen crosslinking (CXL) is a commonly used minimally invasive surgical technique to prevent the progression of corneal ectasias, such as keratoconus. Unfortunately, riboflavin/UV-A light-based CXL procedures have not been successfully applied to all patients, and result in frequent complications, such as corneal haze and endothelial damage. We propose a new method for corneal crosslinking by using a Ruthenium (Ru) based water-soluble photoinitiator and visible light (430 nm). Tris(bipyridine)ruthenium(II) ([Ru(bpy)(3)](2+)) and sodium persulfate (SPS) mixture covalently crosslinks free tyrosine, histidine, and lysine groups under visible light (400-450 nm), which prevents UV-A light-induced cytotoxicity in an efficient and time saving collagen crosslinking procedure. In this study, we investigated the effects of the Ru/visible blue light procedure on the viability and toxicity of human corneal epithelium, limbal, and stromal cells. Then bovine corneas crosslinked with ruthenium mixture and visible light were characterized, and their biomechanical properties were compared with the customized riboflavin/UV-A crosslinking approach in the clinics. Crosslinked corneas with a ruthenium-based CXL approach showed significantly higher young's modulus compared to riboflavin/UV-A light-based method applied to corneas. In addition, crosslinked corneas with both methods were characterized to evaluate the hydrodynamic behavior, optical transparency, and enzymatic resistance. In all biomechanical, biochemical, and optical tests used here, corneas that were crosslinked with ruthenium-based approach demonstrated better results than that of corneas crosslinked with riboflavin/ UV-A. This study is promising to be translated into a non-surgical therapy for all ectatic corneal pathologies as a result of mild conditions introduced here with visible light exposure and a nontoxic ruthenium-based photoinitiator to the cornea. Statement of significance Keratoconus, one of the most frequent corneal diseases, could be treated with riboflavin and ultraviolet light-based photo-crosslinking application to the cornea of the patients. Unfortunately, this method has irreversible side effects and cannot be applied to all keratoconus patients. In this study, we exploited the photoactivation behavior of an organoruthenium compound to achieve corneal crosslinking. Ruthenium-based organic complex under visible light demonstrated significantly better biocompatibility and superior biomechanical results than riboflavin and ultraviolet light application. This study promises to translate into a new fast, efficient non-surgical therapy option for all ectatic corneal pathologies. (c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.Publication Metadata only Segmentation of arteries in mprage images of the ventral medial prefrontal cortex(Elsevier, 2008) Penumetcha, N.; Jedynak, B.; Hosakere, M.; Botteron, K. N.; Ratnanather, J. T.; Department of Mathematics; Ceyhan, Elvan; Faculty Member; Department of Mathematics; College of Sciences; N/AA method for removing arteries that appear bright with intensities similar to white matter in Magnetized Prepared Rapid Gradient Echo images of the ventral medial prefrontal cortex is described. The Fast Marching method is used to generate a curve within the artery. Then, the largest connected component is selected to segment the artery which is used to mask the image. The surface reconstructed from the masked image yielded cortical thickness maps similar to those generated by manually pruning the arteries from surfaces reconstructed from the original image. The method may be useful in masking vasculature in other cortical regions. (c) 2007 Elsevier Ltd. All rights reserved.