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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/3
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Publication Metadata only Suppression of segmental chain dynamics on a particle's surface in well-dispersed polymer nanocomposites(AMER CHEMICAL SOC, 2024) Kim, Jihyuk; Thompson, Benjamin R.; Tominaga, Taiki; Osawa, Takahito; Egami, Takeshi; Foerster, Stephan; Ohl, Michael; Faraone, Antonio; Wagner, Norman J.; Department of Chemical and Biological Engineering; Şenses, Erkan; Department of Chemical and Biological Engineering; College of EngineeringThe Rouse dynamics of polymer chains in model nanocomposite polyethylene oxide/silica nanoparticles (NPs) was investigated using quasielastic neutron scattering. The apparent Rouse rate of the polymer chains decreases as the particle loading increases. However, there is no evidence of an immobile segment population on the probed time scale of tens of ps. The slowing down of the dynamics is interpreted in terms of modified Rouse models for the chains in the NP interphase region. Thus, two chain populations, one bulk-like and the other characterized by a suppression of Rouse modes, are identified. The spatial extent of the interphase region is estimated to be about twice the adsorbed layer thickness, or approximate to 2 nm. These findings provide a detailed description of the suppression of the chain dynamics on the surface of NPs. These results are relevant insights on surface effects and confinement and provide a foundation for the understanding of the rheological properties of polymer nanocomposites with well-dispersed NPs.Publication Metadata only Neurodevelopmental disorders and cancer networks share pathways, but differ in mechanisms, signaling strength, and outcome(Nature Portfolio, 2023) Yavuz, Bengi Ruken; Arici, M. Kaan; Demirel, Habibe Cansu; Tsai, Chung-Jung; Jang, Hyunbum; Nussinov, Ruth; Department of Chemical and Biological Engineering; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); College of Engineering; School of MedicineEpidemiological studies suggest that individuals with neurodevelopmental disorders (NDDs) are more prone to develop certain types of cancer. Notably, however, the case statistics can be impacted by late discovery of cancer in individuals afflicted with NDDs, such as intellectual disorders, autism, and schizophrenia, which may bias the numbers. As to NDD-associated mutations, in most cases, they are germline while cancer mutations are sporadic, emerging during life. However, somatic mosaicism can spur NDDs, and cancer-related mutations can be germline. NDDs and cancer share proteins, pathways, and mutations. Here we ask (i) exactly which features they share, and (ii) how, despite their commonalities, they differ in clinical outcomes. To tackle these questions, we employed a statistical framework followed by network analysis. Our thorough exploration of the mutations, reconstructed disease-specific networks, pathways, and transcriptome levels and profiles of autism spectrum disorder (ASD) and cancers, point to signaling strength as the key factor: strong signaling promotes cell proliferation in cancer, and weaker (moderate) signaling impacts differentiation in ASD. Thus, we suggest that signaling strength, not activating mutations, can decide clinical outcome.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 Dynamically driven correlations in elastic net models reveal sequence of events and causality in proteins(John Wiley and Sons Inc, 2024) Erkip Albert; Department of Chemical and Biological Engineering; Erman, Burak; Department of Chemical and Biological Engineering; College of EngineeringAn explicit analytic solution is given for the Langevin equation applied to the Gauss-ian Network Model of a protein subjected to both a random and a deterministic peri-odic force. Synchronous and asynchronous components of time correlation functionsare derived and an expression for phase differences in the time correlations of resi-due pairs is obtained. The synchronous component enables the determination ofdynamic communities within the protein structure. The asynchronous componentreveals causality, where the time correlation function between residues i and j differsdepending on whether i is observed before j or vice versa, resulting in directionalinformation flow. Driver and driven residues in the allosteric process of cyclophilin Aand human NAD-dependent isocitrate dehydrogenase are determined by a perturba-tion-scanning technique. Factors affecting phase differences between fluctuations ofresidues, such as network topology, connectivity, and residue centrality, are identi-fied. Within the constraints of the isotropic Gaussian Network Model, our resultsshow that asynchronicity increases with viscosity and distance between residues,decreases with increasing connectivity, and decreases with increasing levels of eigen-vector centrality.Publication Metadata only High-throughput computational screening of MOF adsorbents for efficient propane capture from air and natural gas mixtures(AIP Publishing, 2024) Department of Chemical and Biological Engineering; Erçakır, Göktuğ; Aksu, Gökhan Önder; Keskin, Seda; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of EngineeringIn this study, we used a high-throughput computational screening approach to examine the potential of metal-organic frameworks (MOFs) for capturing propane (C3H8) from different gas mixtures. We focused on Quantum MOF (QMOF) database composed of both synthesized and hypothetical MOFs and performed Grand Canonical Monte Carlo (GCMC) simulations to compute C3H8/N2/O2/Ar and C3H8/C2H6/CH4 mixture adsorption properties of MOFs. The separation of C3H8 from air mixture and the simultaneous separation of C3H8 and C2H6 from CH4 were studied for six different adsorption-based processes at various temperatures and pressures, including vacuum-swing adsorption (VSA), pressure-swing adsorption (PSA), vacuum-temperature swing adsorption (VTSA), and pressure-temperature swing adsorption (PTSA). The results of molecular simulations were used to evaluate the MOF adsorbents and the type of separation processes based on selectivity, working capacity, adsorbent performance score, and regenerability. Our results showed that VTSA is the most effective process since many MOFs offer high regenerability (>90%) combined with high C3H8 selectivity (>7 x 103) and high C2H6 + C3H8 selectivity (>100) for C3H8 capture from air and natural gas mixtures, respectively. Analysis of the top MOFs revealed that materials with narrow pores (<10 angstrom) and low porosities (<0.7), having aromatic ring linkers, alumina or zinc metal nodes, typically exhibit a superior C3H8 separation performance. The top MOFs were shown to outperform commercial zeolite, MFI for C3H8 capture from air, and several well-known MOFs for C3H8 capture from natural gas stream. These results will direct the experimental efforts to the most efficient C3H8 capture processes by providing key molecular insights into selecting the most useful adsorbents.Publication Metadata only Attenuation of Type IV pili activity by natural products(Taylor & Francis Inc, 2024) Yalkut, Kerem; Hassine, Soumaya Ben Ali; Kula, Ceyda; Ozcan, Aslihan; Avci, Fatma Gizem; Akbulut, Berna Sariyar; Ozbek, Pemra; Department of Chemical and Biological Engineering; Başaran, Esra; Keskin, Özlem; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of EngineeringThe virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control P. aeruginosa infections. Here, a computational approach has been pursued to screen natural products that can be used for this purpose. PilB, the elongation ATPase of the T4P machinery in P. aeruginosa, has been selected as the target subunit and virtual screening of FDA-approved drugs has been conducted. Screening identified two natural compounds, ergoloid and irinotecan, as potential candidates for inhibiting this T4P-associated ATPase in P. aeruginosa. These candidate compounds underwent further rigorous evaluation through molecular dynamics (MD) simulations and then through in vitro twitching motility and biofilm inhibition assays. Notably, ergoloid emerged as a particularly promising candidate for weakening the T4P activity by inhibiting the elongation ATPases associated with T4P. This repurposing study paves the way for the timely discovery of antivirulence drugs as an alternative to classical antibiotic treatments to help combat infections caused by P. aeruginosa and related pathogens.Publication Metadata only Review: cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide(Frontiers Media Sa, 2024) Nussinov, Ruth; Yavuz, Bengi Ruken; Arıcı, M. Kaan; Jang, Hyunbum; Department of Chemical and Biological Engineering; Demirel, Habibe Cansu; Tunçbağ, Nurcan; 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 EngineeringThe connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do individuals with neurodevelopmental disorders, such as autism and schizophrenia, face higher chances of cancer emerging throughout their lifetime? Our broad review emphasizes the multi-scale aspect of this type of reasoning. As these examples demonstrate, rather than focusing on a specific organ system or disease, we aim at the new understanding that can be gained. Within this framework, our review calls attention to computational strategies which can be powerful in discovering connections, causalities, predicting clinical outcomes, and are vital for drug discovery. Thus, rather than centering on the clinical features, we draw on the rapidly increasing data on the molecular level, including mutations, isoforms, three-dimensional structures, and expression levels of the respective disease-associated genes. Their integrated analysis, together with chromatin states, can delineate how, despite being connected, neurodevelopmental disorders and cancer differ, and how the same mutations can lead to different clinical symptoms. Here, we seek to uncover the emerging connection between cancer, including pediatric tumors, and neurodevelopmental disorders, and the tantalizing questions that this connection raises.Publication Metadata only SETD3 regulates endoderm differentiation of mouse embryonic stem cells through canonical Wnt signaling pathway(Wiley, 2024) Alganatay, Ceren; Balbasi, Emre; Sezginmert, Dersu; Cizmecioglu, Nihal Terzi; Department of Chemical and Biological Engineering; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; College of EngineeringWith self-renewal and pluripotency features, embryonic stem cells (ESCs) provide an invaluable tool to investigate early cell fate decisions. Pluripotency exit and lineage commitment depend on precise regulation of gene expression that requires coordination between transcription (TF) and chromatin factors in response to various signaling pathways. SET domain-containing 3 (SETD3 Delta) is a methyltransferase that can modify histones in the nucleus and actin in the cytoplasm. Through an shRNA screen, we previously identified SETD3 as an important factor in the meso/endodermal lineage commitment of mouse ESCs (mESC). In this study, we identified SETD3-dependent transcriptomic changes during endoderm differentiation of mESCs using time-course RNA-seq analysis. We found that SETD3 is involved in the timely activation of the endoderm-related gene network. The canonical Wnt signaling pathway was one of the markedly altered signaling pathways in the absence of SETD3. The assessment of Wnt transcriptional activity revealed a significant reduction in Setd3-deleted (setd3 increment ) mESCs coincident with a decrease in the nuclear pool of the key TF beta-catenin level, though no change was observed in its mRNA or total protein level. Furthermore, a proximity ligation assay (PLA) found an interaction between SETD3 and beta-catenin. We were able to rescue the differentiation defect by stably re-expressing SETD3 or activating the canonical Wnt signaling pathway by changing mESC culture conditions. Our results suggest that alterations in the canonical Wnt pathway activity and subcellular localization of beta-catenin might contribute to the endoderm differentiation defect of setd3 Delta increment mESCs.Publication Metadata only Reactive capture and electrochemical conversion of CO2 with ionic liquids and deep eutectic solvents(Royal Society of Chemistry, 2024) Dongare, Saudagar; Zeeshan, Muhammad; Dikki, Ruth; Coskun, Oguz Kagan; Munoz, Miguel; Banerjee, Avishek; Gautam, Manu; Ross, R. Dominic; Stanley, Jared S.; Brower, Rowan S.; Muchharla, Baleeswaraiah; Sacci, Robert L.; Velazquez, Jesus M.; Kumar, Bijandra; Yang, Jenny Y.; Hahn, Christopher; Morales-Guio, Carlos G. Spurgeon, Joshua M.; Gurkan, Burcu; Department of Chemical and Biological Engineering; Aydoğdu, Ahmet Safa; Öztulum, Samira Fatma Kurtoğlu; Uzun, Alper; Keskin, Seda; 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; College of EngineeringIonic liquids (ILs) and deep eutectic solvents (DESs) have tremendous potential for reactive capture and conversion (RCC) of CO2 due to their wide electrochemical stability window, low volatility, and high CO2 solubility. There is environmental and economic interest in the direct utilization of the captured CO2 using electrified and modular processes that forgo the thermal- or pressure-swing regeneration steps to concentrate CO2, eliminating the need to compress, transport, or store the gas. The conventional electrochemical conversion of CO2 with aqueous electrolytes presents limited CO2 solubility and high energy requirement to achieve industrially relevant products. Additionally, aqueous systems have competitive hydrogen evolution. In the past decade, there has been significant progress toward the design of ILs and DESs, and their composites to separate CO2 from dilute streams. In parallel, but not necessarily in synergy, there have been studies focused on a few select ILs and DESs for electrochemical reduction of CO2, often diluting them with aqueous or non-aqueous solvents. The resulting electrode-electrolyte interfaces present a complex speciation for RCC. In this review, we describe how the ILs and DESs are tuned for RCC and specifically address the CO2 chemisorption and electroreduction mechanisms. Critical bulk and interfacial properties of ILs and DESs are discussed in the context of RCC, and the potential of these electrolytes are presented through a techno-economic evaluation.Publication Metadata only Dynamically bonded cellulose nanocrystal hydrogels: structure, rheology and fire prevention performance(Elsevier Ltd, 2024) Kaynak-Uraz, Elif; Department of Chemical and Biological Engineering; Şenses, Erkan; Koparipek, Nazlınur Arslan; Department of Chemical and Biological Engineering; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); Koç University Boron and Advanced Materials Application and Research Center (KUBAM) / Koç Üniversitesi Bor ve İleri Malzemeler Uygulama ve Araştırma Merkezi (KUBAM); College of Engineering; Graduate School of Sciences and EngineeringFlame retardant composite hydrogels offer many advantages over conventional flame retardants, such as high water-retention capacity, enhanced fire resistance, and mechanical tunability. Herein, we developed flame-retardant dynamic covalent hydrogels using wood-derived cellulose nanocrystals (CNCs) crosslinked with boronate ester bonds, addressing environmental and health issues associated with the presence of non-biodegradable synthetic polymer and/or inorganic nanoparticle components in the existing systems. Our rheological investigation shows a liquid-to-soft-solid transition of CNC dispersions with tunable network elasticity ranging between ≈ 0.2 kPa to 3.5 kPa and an immediate self-healing ability. Coating pine wood with these hydrogels delayed ignition by about 30 s compared to native wood, and achieved a remarkable limiting oxygen index of 64.5 %. Also, the increased borax content of the gels was found to decrease and delay the first peak of the heat release rate up to 40 s, causing an increase in the fire retardancy index by 277 %. We correlate the microstructure and rheological behavior with the fire prevention mechanisms for the rational design of sustainable fire-retardant materials, and the results showcased a circular use of plant-based dynamic gels to prevent wood fires, even after drying- a feature lacking in conventional hydrogels.