WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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Article Citation - WoS: 3Citation - Scopus: 41,2-Diboranes With Strong Donor Substitutes: Synthesis, Ovicidal and Larvicidal Effect on Important Vector Species(Elsevier, 2024) Bursali, Fatma; Özgener, Hüseyin; Sahin, Yueksel; Aygun, Muhittin; Sevincek, Resul; Biyik, H. Halil; Özgener, Hüseyin; Gurbuz, Burcin; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyNovel control products are needed in the control of important insects like mosquitoes which are developing resistance to insecticides and larvicides currently in the market. Boron compounds have been demonstrated to exhibit antibacterial and anticancer effects. 1,2-diboranes with a long history and importance in boron chemistry have been described. These compounds are synthesized from reactions of 1,2-dichlordiborane derivatives with lidium amides (ArNHLi/Et2NLi, etc.). In addition to the three previously synthesized diborane compounds, five novel 1,2-diborane compounds were synthesized in good yield using the same method for the first time. The structures of the novel derivatives were characterized by nuclear magnetic resonance spectroscopy, and the molecular structure of one of them (2a) was also demonstrated using single crystal X-ray diffraction. In this preliminary study, the ovicidal and larvicidal effects of new 1,2-diamino-1,2-diborane derivatives against Aedes aegypti and Aedes albopictus eggs and larvae were investigated for the first time. Of these, 2a and 2e showed the highest ovicidal activity against both species, while 7, 4 and 2d showed particularly high larvicidal activity. Some 1,2-diborane derivatives were found to be significantly toxic, with LC50 values ranging from 14,930 to 27,975 mu g/mL. Some derivatives (6, 2a, 2c) were less effective against mosquito larvae. 1,2-Diborane derivatives have high ovicidal and larvicidal effects on mosquitoes and are therefore potential candidates for the development of new larvicides. Further studies are needed to evaluate its mode of action and safety. Understanding their mode of action against mosquito development is crucial to optimizing their use and reducing the potential development of resistance. Their potential effects on other mosquito species and non -target organisms need to be investigated.Article Citation - WoS: 6Citation - Scopus: 71,2-Diborolanes With Strong Donor Substituents: Synthesis and High Antimicrobial Activity(Academic Press, 2021) Şahin, Yüksel; Özgener, Hüseyin; Poyrazoğlu Çoban, Esin; Sevinçek, Resul; Bıyık, Halil H.; Özgener, Hüseyin; Aygün, Muhittin; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology1,2-diborolanes with strong and without strong donor substituents have been described, and are also referred to as 1,2-diboracyclopentane. The 1,2-diaryl/alkyl-amino-1,2-diboracyclopentanes 2, 3, and 4 were obtained in good yield after the reaction of 1,2-dichloro-1,2-diboracyclopentane 1 with ArNHLi and Me3Si-NR2. The structures of these new derivatives were characterized by nuclear magnetic resonance spectroscopy. The molecular structures of 2b, 2c, 2e, 4, and 5f were also determined by single-crystal X-ray diffraction. The newly synthesized 1,2-borolanes are stable in air and showed particularly high activity against some Gram-positive bacteria. © 2020 Elsevier Inc.Article Citation - WoS: 2Citation - Scopus: 31-Octanol Is a Functional Impurity Modifying Particle Size and Photophysical Properties of Colloidal Zncdsse/Zns Nanocrystals(American Chemical Society, 2021) Sevim Ünlütürk, Seçil; Özçelik, Serdar; Çağır, Ali; Varlıklı, Canan; Varlıklı, Canan; Çağır, Ali; Özçelik, Serdar; 04.01. Department of Chemistry; 04.04. Department of Photonics; 04. Faculty of Science; 01. Izmir Institute of TechnologyImpurities in trioctylphophine (TOP) strongly affect nanocrystal synthesis. 1-Octanol among other contaminants in TOP is identified for the first time as a functional impurity by H-1 NMR. The deliberate addition of 1-octanol into trioctylphosphine reduced particle size and modified photophysical properties of ZnCdSSe/ZnS colloidal nanocrystals. NMR analysis furthermore revealed that 1-octanol is bonded to the nanocrystal surfaces. The ratio of integrals for the O-CH2 protons of 1-octanol, which is the lowest compared to the other ligands, suggests that 1-octanol plays a critical role to tune the particle size of nanocrystals. The increased amount of 1-octanol added into TOP reduces the particle size from 9.8 to 7.2 nm, causing a progressive blue shift in the UV-vis and PL spectra but leaving the alloy composition unaffected. The rate of nonradiative processes is enhanced with the amount of 1-octanol added into TOP, correlating with higher dislocation density observed in the nanocrystals. As a conclusion, 1-octanol is proposed as a functional impurity that varies particle size and nonradiative photophysical processes in the ZnCdSSe/ZnS colloidal nanocrystals.Article Citation - WoS: 52Citation - Scopus: 581.55 Å-Resolution Structure of Ent-Copalyl Diphosphate Synthase and Exploration of General Acid Function by Site-Directed Mutagenesis(Elsevier, 2014) Köksal, Mustafa; Köksal, Mustafa; Christianson, David W.; Peters, Reuben John; Potter, Kevin; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyBackground The diterpene cyclase ent-copalyl diphosphate synthase (CPS) catalyzes the first committed step in the biosynthesis of gibberellins. The previously reported 2.25 Å resolution crystal structure of CPS complexed with (S)-15-aza-14,15-dihydrogeranylgeranyl thiolodiphosphate (1) established the αβγ domain architecture, but ambiguities regarding substrate analog binding remained. Method Use of crystallization additives yielded CPS crystals diffracting to 1.55 Å resolution. Additionally, active site residues that hydrogen bond with D379, either directly or through hydrogen bonded water molecules, were probed by mutagenesis. Results This work clarifies structure-function relationships that were ambiguous in the lower resolution structure. Well-defined positions for the diphosphate group and tertiary ammonium cation of 1, as well as extensive solvent structure, are observed. Conclusions Two channels involving hydrogen bonded solvent and protein residues lead to the active site, forming hydrogen bonded "proton wires" that link general acid D379 with bulk solvent. These proton wires may facilitate proton transfer with the general acid during catalysis. Activity measurements made with mutant enzymes indicate that N425, which donates a hydrogen bond directly to D379, and T421, which hydrogen bonds with D379 through an intervening solvent molecule, help orient D379 for catalysis. Residues involved in hydrogen bonds with the proton wire, R340 and D503, are also important. Finally, conserved residue E211, which is located near the diphosphate group of 1, is proposed to be a ligand to Mg2 + required for optimal catalytic activity. General significance This work establishes structure-function relationships for class II terpenoid cyclases.Conference Object Citation - WoS: 3Citation - Scopus: 31/F Noise in Amorphous Silicon and Silicon-Germanium Alloys(SPIE, 2003) Johanson, Robert E.; Güneş, Mehmet; Güneş, Mehmet; Kasap, Safa O.; 04.05. Department of Pyhsics; 04. Faculty of Science; 01. Izmir Institute of TechnologyWe report measurements of conductance noise of a-Si1-XGeX:H in two different geometries; one where the current flow is transverse to the surface and the other longitudinal to it. Because of the large increase in sample resistance in going from transverse to longitudinal conduction, it was not possible to measure both geometries at the same temperature. However, the temperature trends are compatible with a common noise source. For both geometries, alloying with up to 40% Ge reduces the noise magnitude by a factor of 50 over that found in a-Si:HArticle Citation - WoS: 10Citation - Scopus: 71/F Noise in Doped and Undoped Amorphous Silicon(Elsevier Ltd., 2000-05) Johanson, Robert E.; Güneş, Mehmet; Güneş, Mehmet; Kasap, Safa O.; 04.05. Department of Pyhsics; 04. Faculty of Science; 01. Izmir Institute of TechnologyWe measured the spectrum of conductance fluctuations in n-type, p-type, and undoped hydrogenated amorphous silicon (a-Si:H) as a function of temperature. In general, the spectra can be fit to a power law, 1/fα, although in the p-type and undoped samples deviations from a strict power law occur. For n-type and p-type samples, the noise magnitude increases with temperature by approximately a factor of 5 from 295 to 450 K. The slope parameter, α, also increases with temperature in the p-type samples from near unity to 1.4 but not in the n-type sample where it remains near 1.05 independent of temperature. The undoped sample could be measured only over a limited range of elevated temperatures, but α does trend larger. The undoped and lightly doped material have similar noise levels but larger p-type doping reduces the noise by two orders of magnitude. Correlation measurements indicate the 1/f noise is Gaussian for all samples. However, intermittent random-telegraph noise is observed in n-type material.Conference Object Citation - WoS: 6Citation - Scopus: 101/F Noise in Hydrogenated Amorphous Silicon-Germanium Alloys(Institute of Electrical and Electronics Engineers, 2003-08) Johanson, Robert E.; Güneş, Mehmet; Güneş, Mehmet; Kasap, Safa O.; 04.05. Department of Pyhsics; 04. Faculty of Science; 01. Izmir Institute of TechnologyMeasurements were made of conductance noise of a-Si:H and a-Si 1-xGex:H in two different geometries: one where the current flow is transverse to the surface and the other where it is longitudinal to the surface. Because of the large change in sample resistance between the two geometries, it was not possible to measure both geometries at the same temperature. For both geometries, alloyinzg with up to 40% Ge reduces the noise magnitude by several orders of magnitude over that found in a-Si:H. The decrease is incompatible with several popular noise models. Extrapolating the temperature trends for each geometry shows that it is possible that the noise observed in the transverse samples has the same origin as the higher frequency part of the double power law spectra observed in the longitudinal samples.Article Citation - WoS: 15Citation - Scopus: 141/F-noise Study of Undoped Intrinsic Hydrogenated Amorphous Silicon Thin Films(American Physical Society, 1999) Güneş, Mehmet; Güneş, Mehmet; Johanson, Robert E.; Kasap, Safa O.; 04.05. Department of Pyhsics; 04. Faculty of Science; 01. Izmir Institute of TechnologyConductance fluctuations in four samples of undoped intrinsic hydrogenated amorphous silicon (a-Si:H) were measured in the temperature range of 450 K to 500 K and for frequencies from 2 Hz to 3 kHz. The noise spectra divide into two regions that each fit a 1/fα power law but with different slope parameters α and different temperature dependences. At low frequencies, α is greater than unity and increases with temperature. At high frequencies, α is near 0.6 and temperature independent, but the noise magnitude decreases rapidly with temperature. We infer from the different dependences on temperature that the noise is generated by two independent mechanisms operating simultaneously in a-Si:H. We also observe that the 1/f noise exhibits a quadratic dependence on bias current and Gaussian statistics.Article 1/Nc Expansion and Anomaly Cancellation in the Presence of Electroweak Interactions(IOP Publishing Ltd., 1998-03) Erdem, Recai; Erdem, Recai; 04.05. Department of Pyhsics; 04. Faculty of Science; 01. Izmir Institute of TechnologyWe study the question of a consistent formulation of the 1/Nc expansion in the presence of electroweak interactions. We show that in some cases the previous formulation leads to an unrealistic picture. We improve the scheme. We derive the corresponding hypercharge and electric charge values of fermions under the requirement that the standard model in the large-Nc limit should be free of chiral gauge anomalies. We find that the resulting hypercharge and the electric charge values for quarks are the same as for the standard model.Conference Object Citation - WoS: 5Citation - Scopus: 6The 1st Workshop on Model-Based Verification & Validation: Directed Acyclic Graph Modeling of Security Policies for Firewall Testing(Institute of Electrical and Electronics Engineers Inc., 2009) Tuğlular, Tuğkan; Belli, Fevzi; Kaya, Özgür; Tuğlular, Tuğkan; Müftüoğlu, Can Arda; Belli, Fevzi; 03.04. Department of Computer Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyCurrently network security of institutions highly depend on firewalls, which are used to separate untrusted network from trusted one by enforcing security policies. Security policies used in firewalls are ordered set of rules where each rule is represented as a predicate and an action. This paper proposes modeling of firewall rules via directed acyclic graphs (DAG), from which test cases can be automatically generated for firewall testing. The approach proposed follows test case generation algorithm developed for event sequence graphs. Under a local area network setup with the aid of a specifically developed software for this purpose, generated test cases are converted to network test packets, test packets are sent to the firewall under test (FUT), and sent packets are compared with passed packets to determine test result.Article 2’-Methylklavuzon Causes Lipid-Lowering Effects on A549 Non-Small Cell Lung Cancer Cells and Significant Changes on Dna Structure Evidenced by Fourier Transform Infrared Spectroscopy(Elsevier, 2020) Ceylan, Çağatay; Çağır, Ali; Aksoy, Hatice Nurdan; Ceylan, Çağatay; Çağır, Ali; Çetinkaya, Hakkı; 03.08. Department of Food Engineering; 04.01. Department of Chemistry; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of TechnologyVarious chemical agents are used in the treatment of Non-Small Cell Lung Cancer (NSCLC). 2?-methylklavuzon was proposed as a potential chemotherapeutic agent in cancer treatment based on its topoisomerase inhibition activity. In this study the cellular effects of 2?-methylklavuzon was evaluated on A549 cancer cells using FTIR spectroscopy. 2?-methylklavuzon induced significant changes on both the whole cell lyophilizates and the lipid extracts of the A549 lung cancer cells. 2?-methylklavuzon caused significant structural changes in A549 cell DNA structure: T, A and G DNA breathing modes are lost after the drug application indicating the loss of topoisomerase activity. The level of transcription and RNA synthesis was enhanced. 2?-methylklavuzon induced single stranded DNA formation evidenced by the increase in the ratio of asymmetric/symmetric phosphate stretching modes. 2?-methylklavuzon induced band shifts only in the asymmetric mode of phosphate bonds not in the symmetrical phosphate bond stretching. 2?-methylklavuzon induced A form of DNA topography. In addition to the changes in the DNA structure and transcription 2?-methylklavuzon also caused lipid-lowering effect in A549 cancer cells. 2?-methylklavuzon suppressed lipid unsaturation, however, it induced formation of lipids with ring structures. 2?-methylklavuzon suppressed phosphate-containing lipids significantly and decreased carbonyl containing lipids and cholesterol slightly. 2?-methylklavuzon caused increases in the hydrocarbon chain length. Overall, 2?-methylklavuzon can be used as a lipid-lowering compound in the treatment of NSCLC and other cancer therapies. © 2020 Elsevier B.V.Article Citation - WoS: 17Citation - Scopus: 162-D Analysis of Ge Implanted Sio2 Surfaces by Laser-Induced Breakdown Spectroscopy(Elsevier Ltd., 2008-10) Yalçın, Şerife; Yalçın, Şerife; Örer, Sabiha; Turan, Raşit; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology2-D elemental distribution of Ge in silicon oxide substrates with differing implantation doses of between 3 × 1016 cm- 2 and 1.5 × 1017 cm- 2 has been investigated by Laser-Induced Breakdown Spectroscopy (LIBS). Spectral emission intensity has been optimized with respect to time, crater size, ablation depth and laser energy. Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) coupled with Energy-Dispersive X-Ray Spectroscopy (EDX) have been utilized to obtain crater depth, morphology and elemental composition of the sample material, respectively. LIBS spectral data revealed the possibility of performing 2-D distribution analysis of Ge atoms in silicon oxide substrate. EDX analysis results confirmed that LIBS is capable to detect Ge atoms at concentrations lower than 0.2% (atomic). LIBS as a fast semi-quantitative analysis method with 50 μm lateral and 800 nm depth resolution has been evaluated. Results illustrate the potential use of LIBS for rapid, on-line assessment of the quality of advanced technology materials during the manufacturing process. © 2008 Elsevier B.V. All rights reserved.Article Citation - WoS: 37Citation - Scopus: 362d Vibrational Properties of Epitaxial Silicene on Ag(111)(IOP Publishing Ltd., 2017-03) Solonenko, Dmytro; Şahin, Hasan; Gordan, Ovidiu D.; Le Lay, Guy; Şahin, Hasan; Cahangirov, Seymur; Zahn, Dietrich R. T.; Vogt, Patrick; 04.04. Department of Photonics; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe two-dimensional silicon allotrope, silicene, could spur the development of new and original concepts in Si-based nanotechnology. Up to now silicene can only be epitaxially synthesized on a supporting substrate such as Ag(111). Even though the structural and electronic properties of these epitaxial silicene layers have been intensively studied, very little is known about its vibrational characteristics. Here, we present a detailed study of epitaxial silicene on Ag(111) using in situ Raman spectroscopy, which is one of the most extensively employed experimental techniques to characterize 2D materials, such as graphene, transition metal dichalcogenides, and black phosphorous. The vibrational fingerprint of epitaxial silicene, in contrast to all previous interpretations, is characterized by three distinct phonon modes with A and E symmetries. Both, energies and symmetries of theses modes are confirmed by ab initio theory calculations. The temperature dependent spectral evolution of these modes demonstrates unique thermal properties of epitaxial silicene and a significant electron-phonon coupling. These results unambiguously support the purely two-dimensional character of epitaxial silicene up to about 300°C, whereupon a 2D-to-3D phase transition takes place. The detailed fingerprint of epitaxial silicene will allow us to identify it in different environments or to study its modifications.Conference Object Citation - Scopus: 13-D Switching Fabric Node Design(ACTA Press, 2004) Dinleyici, Mehmet Salih; Dinleyici, Mehmet Salih; Akın, Osman; 03.05. Department of Electrical and Electronics Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyIn this work we investigate an all-optical switching node that can be controlled by means of a transient grating, which is formed by interference of two Gaussian beams. This design considers 3-D architecture of switching fabrics.. real profile of Gaussian beams and fast switching time requirements. Four Wave Mixing (FWM) technique is applied in the evanescent field region of waveguide, showing chi((3)) nonlinearity. The formed grating is analysed by standart methods to obtain reflection coefficient and then coupling coefficient for power exchange between waveguides.Article Citation - WoS: 10Citation - Scopus: 143D Bioprinting of mouse pre-osteoblasts and human MSCs using bioinks consisting of gelatin and decellularized bone particles(Iop Publishing Ltd, 2024) Kara, Aylin; Kara, Aylin; Distler, Thomas; Tıhmınlıoğlu, Funda; Akkineni, Ashwini Rahul; Tihminlioglu, Funda; Gelinsky, Michael; Boccaccini, Aldo R.; 03.02. Department of Chemical Engineering; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyOne of the key challenges in biofabrication applications is to obtain bioinks that provide a balance between printability, shape fidelity, cell viability, and tissue maturation. Decellularization methods allow the extraction of natural extracellular matrix, preserving tissue-specific matrix proteins. However, the critical challenge in bone decellularization is to preserve both organic (collagen, proteoglycans) and inorganic components (hydroxyapatite) to maintain the natural composition and functionality of bone. Besides, there is a need to investigate the effects of decellularized bone (DB) particles as a tissue-based additive in bioink formulation to develop functional bioinks. Here we evaluated the effect of incorporating DB particles of different sizes (<= 45 and <= 100 mu m) and concentrations (1%, 5%, 10% (wt %)) into bioink formulations containing gelatin (GEL) and pre-osteoblasts (MC3T3-E1) or human mesenchymal stem cells (hTERT-MSCs). In addition, we propose a minimalistic bioink formulation using GEL, DB particles and cells with an easy preparation process resulting in a high cell viability. The printability properties of the inks were evaluated. Additionally, rheological properties were determined with shear thinning and thixotropy tests. The bioprinted constructs were cultured for 28 days. The viability, proliferation, and osteogenic differentiation capacity of cells were evaluated using biochemical assays and fluorescence microscopy. The incorporation of DB particles enhanced cell proliferation and osteogenic differentiation capacity which might be due to the natural collagen and hydroxyapatite content of DB particles. Alkaline phosphatase activity is increased significantly by using DB particles, notably, without an osteogenic induction of the cells. Moreover, fluorescence images display pronounced cell-material interaction and cell attachment inside the constructs. With these promising results, the present minimalistic bioink formulation is envisioned as a potential candidate for bone tissue engineering as a clinically translatable material with straightforward preparation and high cell activity.Article Citation - WoS: 6Citation - Scopus: 83d Electrode Use in Mdc for Enhanced Removal of Boron From Geothermal Water(Elsevier, 2022-05) Gören, Ayşegül Yağmur; Ökten, Hatice Eser; Ökten, Hatice Eser; Gören, Ayşegül Yağmur; 03.07. Department of Environmental Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyMicrobial desalination cell (MDC) is a significantly promising technology due to its simultaneous features of electricity production, wastewater treatment and desalination. In this paper, the three-dimensional (3D) sponge with activated carbon-chitosan (AC-CS) was synthesized to enhance the efficiency of the MDC system. Effects of operating parameters (boron concentration, electrode surface area, catholyte solution, and activated sludge volume) on MDC performance were also investigated. The MDC with 3D AC-CS anode provided a higher power density of 970 mW/m2, boron removal efficiency of 75.9%, and COD removal efficiency of >90% under optimized conditions. The maximum boron and COD removal efficiencies were 65.6 and 81.4% with the power density of 866.9 mW/m2 for geothermal brine. Moreover, BET analysis showed that the 3D AC-CS anode presented high surface area (230 m2/g) and pore volume (0.202 cm3/g). As an overall result, not only the production of 3D sponge anode electrodes with AC-CS composite was achieved but also desalination and power generation results that were comparable with the literature were presented.Correction 3D modelling of surface spreading and underground dam groundwater recharge: Egri creek subbasin, Turkey(Springer, 2023) Şahin, Yavuz; Tayfur, Gökmen; Tayfur, Gökmen; 03.03. Department of Civil Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyArticle Citation - WoS: 4Citation - Scopus: 43d Modelling of Surface Spreading and Underground Dam Groundwater Recharge: Egri Creek Subbasin, Turkey(Springer, 2023) Şahin, Yavuz; Tayfur, Gökmen; Tayfur, Gökmen; 03.03. Department of Civil Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyThis study investigated surface spreading and underground dam recharge methods to replenish groundwater in Turkey's Egri Creek Sub-basin of the Kucuk Menderes River Basin. A three-dimensional numerical model was employed for this purpose. Field and lab data are provided to the model for realistic simulations. Pumping test results were used to determine the aquifer parameters. The laboratory works involved sieve analysis, permeability tests, and porosity and water content prediction. The numerical model's boundary conditions were determined from the geological and hydrogeological characteristics of the study area. Initial conditions were expressed regarding water content and pressure head in the vadose zone. The numerical model was satisfactorily validated by simulating water levels in three different pumping wells in the study area. Seven different scenarios, each having a different pool size, were investigated for the surface spreading recharge method. The results showed that a pool size of 30 x 30 m with a 6-m depth basin was the most optimal choice, raising the groundwater level to about 29.3 m. On the other hand, it was found that an underground dam could raise the levels by an average of 9.5 m, which might not be significant to warrant the construction.Article Citation - WoS: 47Citation - Scopus: 543d Printed Gelatin/Decellularized Bone Composite Scaffolds for Bone Tissue Engineering: Fabrication, Characterization and Cytocompatibility Study(Elsevier, 2022-06) Kara, Aylin; Tıhmınlıoğlu, Funda; Distler, Thomas; Kara, Aylin; Polley, Christian; Schneidereit, Dominik; Seitz, Hermann; Friedrich, Oliver; Tıhmınlıoğlu, Funda; Boccaccini, Aldo R; 03.02. Department of Chemical Engineering; 03.01. Department of Bioengineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyThree-dimensional (3D) printing technology enables the design of personalized scaffolds with tunable pore size and composition. Combining decellularization and 3D printing techniques provides the opportunity to fabricate scaffolds with high potential to mimic native tissue. The aim of this study is to produce novel decellularized bone extracellular matrix (dbECM)-reinforced composite-scaffold that can be used as a biomaterial for bone tissue engineering. Decellularized bone particles (dbPTs, ∼100 μm diameter) were obtained from rabbit femur and used as a reinforcement agent by mixing with gelatin (GEL) in different concentrations. 3D scaffolds were fabricated by using an extrusion-based bioprinter and crosslinking with microbial transglutaminase (mTG) enzyme, followed by freeze-drying to obtain porous structures. Fabricated 3D scaffolds were characterized morphologically, mechanically, and chemically. Furthermore, MC3T3-E1 mouse pre-osteoblast cells were seeded on the dbPTs reinforced GEL scaffolds (GEL/dbPTs) and cultured for 21 days to assess cytocompatibility and cell attachment. We demonstrate the 3D-printability of dbPTs-reinforced GEL hydrogels and the achievement of homogenous distribution of the dbPTs in the whole scaffold structure, as well as bioactivity and cytocompatibility of GEL/dbPTs scaffolds. It was shown that Young's modulus and degradation rate of scaffolds were enhanced with increasing dbPTs content. Multiphoton microscopy imaging displayed the interaction of cells with dbPTs, indicating attachment and proliferation of cells around the particles as well as into the GEL-particle hydrogels. Our results demonstrate that GEL/dbPTs hydrogel formulations have potential for bone tissue engineering.Article Citation - WoS: 48Citation - Scopus: 485-Fluorouracil Signaling Through a Calcium-Calmodulin Pathway Is Required for P53 Activation and Apoptosis in Colon Carcinoma Cells(Nature Publishing Group, 2013-09) Can, G.; Baran, Yusuf; Akpınar, B.; Baran, Yusuf; Zhivotovsky, B.; Olsson, M.; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca 2+) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca 2+ through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca 2+ -chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53 -/- cells confirmed the importance of a Ca 2+ -CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes. © 2013 Macmillan Publishers Limited.
