Publications with Fulltext
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 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 Improving CO2 separation performance of MIL-53(Al) by incorporating 1-N-Butyl-3-methylimidazolium methyl sulfate(Wiley, 2019) Department of Chemical and Biological Engineering; N/A; Kulak, Harun; Polat, Hüsamettin Mert; Kavak, Safiyye; Keskin, Seda; Uzun, Alper; 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; N/A; N/A; N/A; 40548; 599171-n-Butyl-3-methylimidazolium methyl sulfate is incorporated into MIL-53(Al). Detailed characterization is done by X-ray fluorescence, Brunauer-Emmett-Teller surface area, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Results show that ionic liquid (IL) interacts directly with the framework, significantly modifying the electronic environment of MIL-53(Al). Based on the volumetric gas adsorption measurements, CO2, CH4, and N-2 adsorption capacities decreased from 112.0, 46.4, and 19.6 cc (STP) g(MIL-53(Al))(-1) to 42.2, 13.0, and 4.3 cc (STP) g(MIL-53(Al))(-1) at 5 bar, respectively, upon IL incorporation. Data show that this postsynthesis modification leads to more than two and threefold increase in the ideal selectivity for CO2 over CH4 and N-2 separations, respectively, as compared with pristine MIL-53(Al). The isosteric heat of adsorption (Qst) values show that IL incorporation increases CO2 affinity and decreases CH4 and N-2 affinities. Cycling adsorption-desorption measurements show that the composite could be regenerated with almost no decrease in the CO2 adsorption capacity for six cycles and confirm the lack of any significant IL leaching. The results offer MIL-53(Al) as an excellent platform for the development of a new class of IL/MOF composites with exceptional performance for CO2 separation.Publication Open Access Engineering human stellate cells for beta cell replacement therapy promotes in vivo recruitment of regulatory T cells(Elsevier, 2019) N/A; Department of Chemical and Biological Engineering; Oran, Dilem Ceren; Lokumcu, Tolga; Bal, Tuğba; İnceoğlu, Yasemin; Albayrak, Özgür; Erkan, Murat Mert; Kurtoğlu, Metin; Can, Füsun; Önder, Tuğba Bağcı; Kızılel, Seda; Akolpoğlu, Mükrime Birgül; Faculty Member; Faculty Member; Master Student; 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 Health Sciences; College of Engineering; School of Medicine; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 103165; 184359; 28376; N/AType 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance.Publication Open Access Al2O3 micro- and nanostructures affect vascular cell response(Royal Society of Chemistry (RSC), 2016) Kiefer, Karin; Akpınar, Gürler; Haidar, Ayman; Ikier, Tuba; Akkan, Çağrı Kaan; Akman, Erhan; Lee, Juseok; Miro, Marina Martinez; Kaçar, Elif; Demir, Arif; Veith, Michael; Kasap, Murat; Kesmez, Mehmet; Abdul-Khaliq, Hashim; Aktaş, Cenk; N/A; Ural, Dilek; Faculty Member; School of Medicine; 1057In-stent restenosis (ISR) is one of the most common and serious complications observed after stent implantation. ISR is characterized by the inordinate proliferation of smooth muscle cells (SMC) that leads to narrowing of the blood vessels. To achieve a healthy endothelium, it is critical to selectively enhance the growth of endothelial cells (EC) while suppressing the growth of smooth muscle cells, which is still a major challenge and yet to be achieved. In this study, novel surfaces have been developed to support the selective growth of endothelial cells. Micro-and nanostructured Al2O3 surfaces with unique topographical features were fabricated and tested. Surface characterization and cellular response of endothelial cells (HUVEC) as well as smooth muscle cells (HUVSMC) has been investigated at cellular and molecular levels. A topography driven selective cell response of ECs over SMCs was demonstrated successfully. This selective response of ECs was also analyzed at protein levels in order to understand the basic mechanism.Publication Open Access Tree-stack LSTM in transition based dependency parsing(Association for Computational Linguistics (ACL), 2018) Department of Computer Engineering; N/A; Yüret, Deniz; Faculty Member; Department of Computer Engineering; College of Engineering; Graduate School of Sciences and Engineering; 179996; N/AWe introduce tree-stack LSTM to model state of a transition based parser with recurrent neural networks. Tree-stack LSTM does not use any parse tree based or hand-crafted features, yet performs better than models with these features. We also develop new set of embeddings from raw features to enhance the performance. There are 4 main components of this model: stack's σ-LSTM, buffer's βLSTM, actions' LSTM and tree-RNN. All LSTMs use continuous dense feature vectors (embeddings) as an input. Tree-RNN updates these embeddings based on transitions. We show that our model improves performance with low resource languages compared with its predecessors. We participate in CoNLL 2018 UD Shared Task as the”KParse” team and ranked 16th in LAS, 15th in BLAS and BLEX metrics, of 27 participants parsing 82 test sets from 57 languages.Publication Open Access Weakening the strength of CO binding on subsurface alloyed Pt(111)(Elsevier, 2019) Ogasawara, Hirohito; Department of Chemistry; N/A; Kaya, Sarp; Gürlek, Sezen; Panahi, Mohammad; Solati, Navid; Faculty Member; PhD Student; Department of Chemistry; Koç University Tüpraş Energy Center (KUTEM) / Koç Üniversitesi Tüpraş Enerji Merkezi (KÜTEM); College of Sciences; Graduate School of Sciences and Engineering; 116541; N/A; N/A; N/AThe interaction of CO with Pt/3d/Pt(111) subsurface alloys (3d: Ni, Co, Fe) was investigated by combination of vibrational spectroscopy and temperature programmed desorption. The binding strength of CO is significantly reduced on Pt/Fe/Pt(111) and Pt/Co/Pt(111) and is sorted in the following order: Pt >Ni > Co approximate to Fe. Our analysis shows that the 3d admetal is stable in the subsurface region and CO is linearly bonded to the atop sites of the Pt(111) surface. At high CO coverage, compressed structures are obtained. At low CO coverage, the desorption activation energy of CO (similar to 143 kJ/mol for Pt(111)) drops to 124 kJ/mol for Pt/Ni/Pt(111), and goes further down to 111 and 110 kJ/mol for Pt/Co/Pt(111) and Pt/Fe/Pt(111), respectively. The enhancement in the surface activity is attributed to the modified backdonation to the antibonding states of adsorbed CO due to the downshifted 5d-band center of Pt upon embedding 3d metals in the subsurface region.Publication Open Access Dynamic accommodation measurement using Purkinje reflections and ML algorithms(Society of Photo-optical Instrumentation Engineers (SPIE), 2023) Department of Electrical and Electronics Engineering; N/A; Aygün, Uğur; Şahin, Afsun; Ürey, Hakan; Faculty Member; Faculty Member; Department of Electrical and Electronics Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; School of Medicine; N/A; N/A; N/A; 171267; 8579We developed a prototype device for dynamic gaze and accommodation measurements based on 4 Purkinje reflections (PR) suitable for use in AR and ophthalmology applications. PR1&2 and PR3&4 are used for accurate gaze and accommodation measurements, respectively. Our eye-model was developed in Zemax and matches the experiments well. Our model predicts the accommodation from 25cm to infinity (<4 diopters) with better than 0,25D accuracy. We performed repeatability tests and obtained accurate gaze and accommodation estimations using 15 subjects. We are generating a large synthetic data set using physically accurate models and machine learning algorithms.Publication Open Access Nanoengineering InP quantum dot-based photoactive biointerfaces for optical control of neurons(Frontiers, 2021) Ulgut, Burak; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; N/A; Nizamoğlu, Sedat; Kavaklı, İbrahim Halil; Şahin, Afsun; Karatüm, Onuralp; Aria, Mohammad Mohammadi; Eren, Güncem Özgün; Yıldız, Erdost; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Sürme, Saliha; Doğru-Yüksel, Itır Bakış; Jalali, Houman Bahmani; Faculty Member; Faculty Member; Faculty Member; PhD Student; Researcher; Teaching Faculty; PhD Student; Department of Electrical and Electronics Engineering; 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 Medicine; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; 130295; 40319; 171267; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/ALight-activated biointerfaces provide a non-genetic route for effective control of neural activity. InP quantum dots (QDs) have a high potential for such biomedical applications due to their uniquely tunable electronic properties, photostability, toxic-heavy-metal-free content, heterostructuring, and solution-processing ability. However, the effect of QD nanostructure and biointerface architecture on the photoelectrical cellular interfacing remained unexplored. Here, we unravel the control of the photoelectrical response of InP QD-based biointerfaces via nanoengineering from QD to device-level. At QD level, thin ZnS shell growth (similar to 0.65 nm) enhances the current level of biointerfaces over an order of magnitude with respect to only InP core QDs. At device-level, band alignment engineering allows for the bidirectional photoelectrochemical current generation, which enables light-induced temporally precise and rapidly reversible action potential generation and hyperpolarization on primary hippocampal neurons. Our findings show that nanoengineering QD-based biointerfaces hold great promise for next-generation neurostimulation devices.Publication Open Access HotRegion: a database of predicted hot spot clusters(Oxford University Press (OUP), 2012) N/A; Department of Computer Engineering; Department of Chemical and Biological Engineering; Çukuroğlu, Engin; Gürsoy, Attila; Keskin, Özlem; PhD Student; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 8745; 26605Hot spots are energetically important residues at protein interfaces and they are not randomly distributed across the interface but rather clustered. These clustered hot spots form hot regions. Hot regions are important for the stability of protein complexes, as well as providing specificity to binding sites. We propose a database called HotRegion, which provides the hot region information of the interfaces by using predicted hot spot residues, and structural properties of these interface residues such as pair potentials of interface residues, accessible surface area (ASA) and relative ASA values of interface residues of both monomer and complex forms of proteins. Also, the 3D visualization of the interface and interactions among hot spot residues are provided.