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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only Deep learning-augmented T-junction droplet generation(Elsevier Inc., 2024) N/A; Department of Mechanical Engineering; Ahmadpour, Abdollah; Shojaeian, Mostafa; Taşoğlu, Savaş; Department of Mechanical Engineering; KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of EngineeringDroplet generation technology has become increasingly important in a wide range of applications, including biotechnology and chemical synthesis. T-junction channels are commonly used for droplet generation due to their integration capability of a larger number of droplet generators in a compact space. In this study, a finite element analysis (FEA) approach is employed to simulate droplet production and its dynamic regimes in a T-junction configuration and collect data for post-processing analysis. Next, image analysis was performed to calculate the droplet length and determine the droplet generation regime. Furthermore, machine learning (ML) and deep learning (DL) algorithms were applied to estimate outputs through examination of input parameters within the simulation range. At the end, a graphical user interface (GUI) was developed for estimation of the droplet characteristics based on inputs, enabling the users to preselect their designs with comparable microfluidic configurations within the studied range.Publication Metadata only Objective-free ultrasensitive biosensing on large-area metamaterial surfaces in the near-IR(AMER CHEMICAL SOC, 2024) Department of Physics; Ramazanoğlu, Serap Aksu; Öktem, Evren; Department of Physics; College of Sciences; Graduate School of Sciences and EngineeringPlasmonic metamaterials have opened new avenues in medical diagnostics. However, the transfer of the technology to the markets has been delayed due to multiple challenges. The need of bulky optics for signal reading from nanostructures patterned on submillimeter area limits the miniaturization of the devices. The use of objective-free optics can solve this problem, which necessitates large area patterning of the nanostructures. In this work, we utilize laser interference lithography (LIL) to pattern nanodisc-shaped metamaterial absorber nanoantennas over a large area (4 cm(2)) within minutes. The introduction of a sacrificial layer during the fabrication process enables an inverted hole profile and a well-controlled liftoff, which ensures perfectly defined uniform nanopatterning almost with no defects. Furthermore, we use a macroscopic reflection probe for optical characterization in the near-IR, including the detection of the binding kinematics of immunologically relevant proteins. We show that the photonic quality of the plasmonic nanoantennas commensurates with electron-beam-lithography-fabricated ones over the whole area. The refractive index sensitivity of the LIL-fabricated metasurface is determined as 685 nm per refractive index unit, which demonstrates ultrasensitive detection. Moreover, the fabricated surfaces can be used multiple times for biosensing without losing their optical quality. The combination of rapid and large area nanofabrication with a simple optical reading not only simplifies the detection process but also makes the biosensors more environmentally friendly and cost-effective. Therefore, the improvements provided in this work will empower researchers and industries for accurate and real-time analysis of biological systems.Publication Metadata only Endometriosis and adenomyosis: shared pathophysiology(Elsevier Science Inc, 2023) Bulun, Serdar E.; Adli, Mazhar; Chakravarti, Debabrata; Parker, James Brandon; Milad, Magdy; Yang, Linda; Chaudhari, Angela; Tsai, Susan; Wei, Jian Jun; Yin, Ping; Yıldız, Şule; School of MedicineEndometriosis and adenomyosis are closely related disorders. Their pathophysiologies are extremely similar. Both tissues originate from the eutopically located intracavitary endometrium. Oligoclones of endometrial glandular epithelial cells with somatic mutations and attached stromal cells may give rise to endometriosis if they travel to peritoneal surfaces or the ovary via retrograde menstruation and/or may be entrapped in the myometrium to give rise to adenomyosis. In both instances, the endometrial cell populations possess survival and growth capabilities conferred by somatic epithelial mutations and epigenetic abnormalities in stromal cells. Activating mutations of KRAS are the most commonly found genetic variant in endometriotic epithelial cells, whereas the adenomyotic epithelial cells almost exclusively bear KRAS mutations. Epigenetic abnormalities in the stromal cells of endometriosis and adenomyosis are very similar and involve an abnormal expression pattern of nuclear receptors, including the steroid receptors. These epigenetic defects give rise to excessive local estrogen biosynthesis by aromatase and abnormal estrogen action via estrogen receptor-b. Deficient progesterone receptor expression results in progesterone resistance in both endometriosis and adenomyosis.Publication Metadata only Adenomyosis: single-cell transcriptomic analysis reveals a paracrine mesenchymal-epithelial interaction involving the WNT/SFRP pathway(Elsevier Science Inc, 2023) Kinali, Meric; Wei, Jian Jun; Milad, Magdy; Yin, Ping; Adli, Mazhar; Bulun, Serdar E.; Yıldız, Şule; School of MedicineObjective: To assess the cellular and molecular landscape of adenomyosis.Design: Single-cell analysis of genome-wide messenger RNA (mRNA) expression (single-cell RNA sequencing) of matched tissues of endometrium, adenomyosis, and myometrium using relatively large numbers of viable cells.Setting: Not applicable. Patient(s): Patients (n 1/4 3, age range 40-44 years) undergoing hysterectomy for diffuse adenomyosis. Main Outcome Measure(s): Definition of the molecular landscape of matched adenomyotic, endometrial and myometrial tissues from the same uterus using single-cell RNA sequencing and comparison of distinct cell types in these tissues to identify disease-specific cell populations, abnormal gene expression and pathway activation, and mesenchymal-epithelial interactions.Result(s): The largest cell population in the endometrium was composed of closely clustered fibroblast groups, which comprise 36% of all cells and seem to originate from pericyte progenitors differentiating to estrogen/progesterone receptor-expressing endometrial stromal-cells. In contrast, the entire fibroblast population in adenomyosis comprised a larger (50%) portion of all cells and was not linked to any pericyte progenitors. Adenomyotic fibroblasts eventually differentiate into extracellular matrix protein-expressing fibroblasts and smooth muscle cells. Hierarchical clustering of mRNA expression revealed a unique adenomyotic fibroblast population that clustered transcriptomically with endometrial fibroblasts, suggestive of an endometrial stromal cell population serving as progenitors of adenomyosis. Four other adenomyotic fibroblast clusters with disease-specific transcriptomes were distinct from those of endometrial or myometrial fibroblasts. The mRNA levels of the natural WNT inhibitors, named, secreted frizzled-related proteins 1, 2, and 4, were higher in these 4 adenomyotic fibroblast clusters than in endometrial fibroblast clusters. Moreover, we found that multiple WNTs, which originate from fibroblasts and target ciliated and unciliated epithelial cells and endothelial cells, constitute a critical paracrine signaling network in adenomyotic tissue. Compared with endometrial tissue, unciliated and ciliated epithelial cells in adenomyosis comprised a significantly smaller portion of this tissue and exhibited molecular evidence of progesterone resistance and diminished regulation of estrogen signaling.Conclusion(s): We found a high degree of heterogeneity in fibroblast-like cells in the adenomyotic uterus. The WNT signaling involving differential expression of secreted frizzled-related proteins, which act as decoy receptors for WNTs, in adenomyotic fibroblasts may have a key role in the pathophysiology of this disease.Publication Metadata only Pediatric-onset chronic inflammatory demyelinating polyneuropathy: a multicenter study(Elsevier Science Inc, 2023) Uzan, Gamze Sarikaya; Yuksel, Deniz; Aksoy, Erhan; Oztoprak, Ulkuhan; Canpolat, Mehmet; Ozturk, Selcan; Yildirim, Celebi; Gulec, Ayten; Per, Huseyin; Gumus, Hakan; Okuyaz, Cetin; Direk, Meltem Cobanoullari; Kosmur, Mustafa; Unalp, Aycan; Yilmaz, Unsal; Bektas, Omer; Teber, Serap; Aliyeva, Nargiz; Dundar, Nihal Olgac; Gencpinar, Pinar; Gurkas, Esra; Yilmaz, Sanem Keskin; Kanmaz, Seda; Tekgtil, Hasan; Aksoy, Ayse; Tuncer, Gokcen Oz; Arslan, Elif Acar; Tosun, Ayse; Ayanoglu, Muge; Bodur, Muhittin; Unay, Bulent; Kurul, Semra Hiz; Yis, Uluc; Vural, Atay; Yousefi, Mohammadreza; Kızılırmak, Ali Burak; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health SciencesBackground: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. Methods: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. Results: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 4 4.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). Conclusions: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.Publication Metadata only TW68, cryptochromes stabilizer, regulates fasting blood glucose levels in diabetic ob/ob and high fat-diet-induced obese mice(Pergamon-Elsevier Science Ltd, 2023) Gul, Seref; Akyel, Yasemin Kubra; Ipek, Ozgecan Savlug; Akarlar, Busra Aytul; Taskin, Ali Cihan; Goren, Ahmet Ceyhan; Baris, Ibrahim; Ozturk, Nuri; Guzel, Mustafa; Aydin, Cihan; Okyar, Alper; Department of Molecular Biology and Genetics; Sürme, Saliha; Ayva, Çağla Ergün; Gül, Zeynep Melis; Özcan, Onur; Türkay, Metin; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and EngineeringCryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the po-tential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS Bmal1-dLuc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 (PCK1) and Glucose-6-phosphatase (G6PC), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting diabetic animals from ob/ob and HFD-fed obese mice, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc. These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo, suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus.Publication Metadata only Magnetic mesoporous janus microrollers for combined chemo- and photothermal ablation therapy(John Wiley and Sons Inc, 2023) Aybar Tural, Gulsen; Bozuyuk, Ugur; Dogan, Nihal Olcay; Alapan, Yunus; Akolpoglu, Mukrime Birgul; Aghakhani, Amirreza; Lazovic, Jelena; Ozer, Ozgen; Department of Mechanical Engineering; Sitti, Metin; Department of Mechanical Engineering; College of Engineering; School of MedicineMobile microrobots have been proposed as a promising approach to overcome the limitations of traditional drug/gene delivery systems. Magnetically actuated surface rolling microrobots, or magnetic surface microrollers, have shown potential for navigation in physiologically relevant environments due to their robust locomotion characteristics. Although much is known about their locomotion abilities in various environments, the full extent of their potential in medical applications has yet to be fully explored. Here, the potential of surface microrollers for combined chemo- and photothermal ablation therapy under medical imaging modalities is demonstrated. The surface microrollers are half-coated with magnetic material, allowing for photothermal heating and magnetic locomotion, and loaded with a biopharmaceutics classification system (BCS) class IV anti-cancer drug, Docetaxel (DTX), for combined therapy. Synergistic action of on-demand photothermal ablation and the controlled release of DTX result in the efficient elimination of cancer cells. Furthermore, microrollers can be detected ex vivo with magnetic resonance imaging (MRI) and photoacoustic imaging (PA), highlighting the potential of surface microrollers for future targeted medical applications.Publication Metadata only Unveiling hidden connections in omics data via pyPARAGON: an integrative hybrid approach for disease network construction(Oxford University Press, 2024) Arici, Muslum Kaan; Department of Chemical and Biological Engineering; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; School of MedicineNetwork inference or reconstruction algorithms play an integral role in successfully analyzing and identifying causal relationships between omics hits for detecting dysregulated and altered signaling components in various contexts, encompassing disease states and drug perturbations. However, accurate representation of signaling networks and identification of context-specific interactions within sparse omics datasets in complex interactomes pose significant challenges in integrative approaches. To address these challenges, we present pyPARAGON (PAgeRAnk-flux on Graphlet-guided network for multi-Omic data integratioN), a novel tool that combines network propagation with graphlets. pyPARAGON enhances accuracy and minimizes the inclusion of nonspecific interactions in signaling networks by utilizing network rather than relying on pairwise connections among proteins. Through comprehensive evaluations on benchmark signaling pathways, we demonstrate that pyPARAGON outperforms state-of-the-art approaches in node propagation and edge inference. Furthermore, pyPARAGON exhibits promising performance in discovering cancer driver networks. Notably, we demonstrate its utility in network-based stratification of patient tumors by integrating phosphoproteomic data from 105 breast cancer tumors with the interactome and demonstrating tumor-specific signaling pathways. Overall, pyPARAGON is a novel tool for analyzing and integrating multi-omic data in the context of signaling networks.Publication Metadata only Effect of finger moisture on tactile perception of electroadhesion(Institute of Electrical and Electronics Engineers, 2024) Lefevre, Philippe; Martinsen, Orjan Grottem; Department of Mechanical Engineering; Aliabbasi, Easa; Muzammil, Muhammad; Şirin, Ömer; Başdoğan, Çağatay; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of EngineeringWe investigate the effect of finger moisture on the tactile perception of electroadhesion with 10 participants. Participants with moist fingers exhibited markedly higher threshold levels. Our electrical impedance measurements show a substantial reduction in impedance magnitude when sweat is present at the finger-touchscreen interface, indicating increased conductivity. Supporting this, our mechanical friction measurements show that the relative increase in electrostatic force due to electroadhesion is lower for a moist finger.Publication Metadata only Doxorubicin-loaded liposome-like particles embedded in chitosan/hyaluronic acid-based hydrogels as a controlled drug release model for local treatment of glioblastoma(Elsevier B.V., 2024) Adiguzel, Seyfure; Karamese, Miray; Kugu, Senanur; Kacar, Elif Ayse; Esen, Muhammed Fevzi; Erdogan, Hakan; Bacanli, Merve Güdül; Altuntas, Sevde; Department of Mechanical Engineering; Taşoğlu, Savaş; Department of Mechanical Engineering; College of EngineeringGlioblastoma (GBM) resection and medication treatment are limited, and local drug therapies are required. This study aims to create a hybrid system comprising liposome-like particles (LLP-DOX) encapsulated in chitosan/hyaluronic acid/polyethyleneimine (CHI/HA/PEI) hydrogels, enabling controlled local delivery of doxorubicin (DOX) into the resection cavity for treating GBM. CHI/HA/PEI hydrogels were characterized morphologically, physically, chemically, mechanically, and thermally. Findings revealed a high network and compact micro-network structure, along with enhanced physical and thermal stability compared to CHI/HA hydrogels. Simultaneously, drug release from CHI/HA/PEI/LLP-DOX hydrogels was assessed, revealing continuous and controlled release up to the 148th hour, with no significant burst release. Cell studies showed that CHI/HA/PEI hydrogels are biocompatible with low genotoxicity. Additionally, LLP-DOX-loaded CHI/HA/PEI hydrogels significantly decreased cell viability and gene expression levels compared to LLP-DOX alone. It was also observed that the viability of GBM spheroids decreased over time when interacting with CHI/HA/PEI/LLP-DOX hydrogels, accompanied by a reduction in total surface area and an increase in apoptotic tendencies. In this study, we hypothesized that creating a hybrid drug delivery system by encapsulating DOX-loaded LLPs within a CHI/HA/PEI hydrogel matrix could achieve sustained drug release, improve anticancer efficacy via localized treatment, and effectively mitigate GBM progression for 3D microtissues.