02. Fen Fakültesi / Faculty of Science
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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; Christianson, David W.; Peters, Reuben John; Potter, KevinBackground 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; Kasap, Safa O.We 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; Kasap, Safa O.We 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; Kasap, Safa O.Measurements 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; Johanson, Robert E.; Kasap, Safa O.Conductance 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, RecaiWe 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.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; Aksoy, Hatice Nurdan; Çağır, Ali; Çetinkaya, HakkıVarious 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; Örer, Sabiha; Turan, Raşit2-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; Gordan, Ovidiu D.; Le Lay, Guy; Şahin, Hasan; Cahangirov, Seymur; Zahn, Dietrich R. T.; Vogt, PatrickThe 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.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.; Akpınar, B.; Baran, Yusuf; Zhivotovsky, B.; Olsson, M.5-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.Research Project 5-Sübstitüentli alpha,beta -doymamış laktonların sentezlenmesi ve biyolojik aktivitelerinin incelenmesi(2009) Çağır, Ali; Kasaplar, Pınar; Akçok, İsmail5,6-dihidro-2H-pyran-2-on yapısını içeren birçok doğal ürünün çeşitli biyolojik aktivitelere sahip olduğu bilinmektedir. Bunların en ilginçlerinden olan goniothalamin sağlıklı hücreler üzerinde minimal etkiye sahipken kanserli hücrelerde sitotoksik etkisi olduğu bilinmektedir. Bu çalışmada goniothalaminin stiril sübstitüentinin 2-naftil grubuyla yerdeğiştirilmesiyle oluşacak konformasyonel olarak sınırlandırılmış molekülün (R)- ve (S)- enansiyomerleri 2-naftil aldehitten başlanarak literaturde bilinen yöntemlerle asimetrik olarak sentezlenmiş, PC-3, MCF-7, DU-145 ve LNCAP kanser hücreleri üzerinde test edilmiştir. Bulgular konformasyonel olarak sınırlandırılmış R enansiyomerinin aktivite üzerinde küçük bir artış gösterdiği yönündedir. 2-Naftil grubu sitiril grubuna göre daha büyük bir grup olduğundan siterik faktörlerin aktivite üzerindeki etkilerinin incelenmeside gerekli görülmüştür.Article Citation - WoS: 31Citation - Scopus: 346-Bicycloaryl Substituted (s)- and (r)-5,6 Asymmetric Synthesis, and Anti-Proliferative Properties(Elsevier Ltd., 2009-01) Kasaplar, Pınar; Yılmazer, Özgür; Çağır, Ali(R)-Goniothalamin, is a member of styryl lactones, possesses selective cytotoxicity against cancer cell lines. In this work, replacement of styryl substituent with 2-naphthyl and 3-quinoyl gave new analogues which may have less conformational changes compared to the lead compound. Anti-proliferative tests indicated that 2-naphthyl substituted (R)-5,6-dihydro-2H-pyran-2-one has slightly better cytotoxicity than (R)-goniothalamin. To clarify the effect of 2-naphthyl substituent additional aryl substituted (R)-5,6-dihydro-2H-pyran-2-ones have been synthesized enantioselectively and tested against PC-3 and MCF-7 cell lines.Article Citation - WoS: 3Citation - Scopus: 3A1-L10 Phase Boundaries and Anisotropy Via Multiple-Order Theory for an Fcc Alloy(European Mathematical Society Publishing House, 2003) Tanoğlu, Gamze; Braun, Richard J.; Cahn, John W.; McFadden, Geoffrey B.The dependence of thermodynamic properties of planar interphase boundaries (IPBs) and antiphase boundaries (APBs) in a binary alloy on an fcc lattice is studied as a function of their orientation. Using a recently developed diffuse interface model based on three non-conserved order parameters and the concentration, and a free energy density that gives a realistic phase diagram with one disordered phase (A1) and two ordered phases (L12 and L10) such as occur in the Cu-Au system, we are able to find IPBs and APBs between any pair of phases and domains, and for all orientations. The model includes bulk and gradient terms in a free energy functional, and assumes that there is no mismatch in the lattice parameters for the disordered and ordered phases.We catalog the appropriate boundary conditions for all IPBs and APBs. We then focus on the IPB between the disordered A1 phase and the L10 ordered phase. For this IPB we compute the numerical solution of the boundary value problem to find its interfacial energy, γ as a function of orientation, temperature, and chemical potential (or composition). We determine the equilibrium shape for a precipitate of one phase within the other using the Cahn-Hoffman "-vector" formalism. We find that the profile of the interface is determined only by one conserved and one non-conserved order parameter, which leads to a surface energy which, as a function of orientation, is "transversely isotropic" with respect to the tetragonal axis of the L10 phase. We verify the model's consistency with the Gibbs adsorption equation.Article Citation - WoS: 43Citation - Scopus: 46Aas, Xrpd, Sem/Eds, and Ftir Characterization of Zn2+ Retention by Calcite, Calcite–kaolinite, and Calcite–clinoptilolite Minerals(Elsevier Ltd., 2005-04-08) Shahwan, Talal; Zünbül, Banu; Tunusoğlu, Özge; Eroğlu, Ahmet EminIn this study, the sorption behavior of Zn2+ on calcite, kaolinite, and clinoptilolite, in addition to mixtures of calcite with kaolinite and clinoptilolite, was investigated at various loadings and mixture compositions using atomic absorption spectroscopy, scanning electron microscopy/energy dispersive X-ray spectroscopy, X-ray powder diffraction, and Fourier transform infrared techniques. According to the obtained results, within the experimental operating conditions, the sorption capacity was enhanced with increasing amount of calcite in both types of mixtures. Under neutral–alkaline pH conditions and high loadings, the order of Zn2+ retention was observed as calcite > clinoptilolite > kaolinite. The experiments on the retention of Zn2+ by pure calcite under conditions of oversaturation showed that the uptake process proceeds via an initial adsorption mechanism (possibly ion-exchange type) followed by a slower mechanism that leads to the overgrowth of the hydrozincite phase, Zn5(OH)6(CO3)2.Article Citation - WoS: 16Citation - Scopus: 17Ab Initio and Semiempirical Modeling of Excitons and Trions in Monolayer Tis3(American Physical Society, 2018-08) Torun, Engin; Şahin, Hasan; Chaves, A.; Wirtz, Ludger; Peeters, François M.We explore the electronic and the optical properties of monolayer TiS3, which shows in-plane anisotropy and is composed of a chain-like structure along one of the lattice directions. Together with its robust direct band gap, which changes very slightly with stacking order and with the thickness of the sample, the anisotropic physical properties of TiS3 make the material very attractive for various device applications. In this study, we present a detailed investigation on the effect of the crystal anisotropy on the excitons and the trions of the TiS3 monolayer. We use many-body perturbation theory to calculate the absorption spectrum of anisotropic TiS3 monolayer by solving the Bethe-Salpeter equation. In parallel, we implement and use a Wannier-Mott model for the excitons that takes into account the anisotropic effective masses and Coulomb screening, which are obtained from ab initio calculations. This model is then extended for the investigation of trion states of monolayer TiS3. Our calculations indicate that the absorption spectrum of monolayer TiS3 drastically depends on the polarization of the incoming light, which excites different excitons with distinct binding energies. In addition, the binding energies of positively and the negatively charged trions are observed to be distinct and they exhibit an anisotropic probability density distribution.Conference Object Citation - WoS: 7Citation - Scopus: 5Abelian Chern-Simons Vortices and Holomorphic Burgers Hierarchy(Pleiades Publishing, 2007-07) Pashaev, Oktay; Gürkan, Zeynep NilhanWe consider the Abelian Chern-Simons gauge field theory in 2+1 dimensions and its relation to the holomorphic Burgers hierarchy. We show that the relation between the complex potential and the complex gauge field as in incompressible and irrotational hydrodynamics has the meaning of the analytic Cole-Hopf transformation, linearizing the Burgers hierarchy and transforming it into the holomorphic Schrödinger hierarchy. The motion of planar vortices in Chern-Simons theory, which appear as pole singularities of the gauge field, then corresponds to the motion of zeros of the hierarchy. We use boost transformations of the complex Galilei group of the hierarchy to construct a rich set of exact solutions describing the integrable dynamics of planar vortices and vortex lattices in terms of generalized Kampe de Feriet and Hermite polynomials. We apply the results to the holomorphic reduction of the Ishimori model and the corresponding hierarchy, describing the dynamics of magnetic vortices and the corresponding lattices in terms of complexified Calogero-Moser models. We find corrections (in terms of Airy functions) to the two-vortex dynamics from the Moyal space-time noncommutativity.Article Citation - WoS: 17Citation - Scopus: 18The Ablowitz-Ladik Lattice System by Means of the Extended (g' / G)-Expansion Method(Elsevier Ltd., 2010-07) Aslan, İsmailWe analyzed the Ablowitz-Ladik lattice system by using the extended (G′ / G)-expansion method. Further discrete soliton and periodic wave solutions with more arbitrary parameters are obtained. We observed that some previously known results can be recovered by assigning special values to the arbitrary parameters. © 2010 Elsevier Inc. All rights reserved.Conference Object Abnormal Gm2 Accumulation Alters the Function of the Autophagic Pathway in Early-Onset Tay-Sachs Disease Mouse Model(Academic Press, 2018) Seyrantepe, Volkan; Ateş, Nurselin; Can, Melike; Şengül, Tuğçe; Akyıldız Demir, SeçilTay-Sachs disease (TSD) is an inborn error of metabolism, a prototypical lysosomal disease of the nervous system. In humans, the fatal infantile acute form is the most common, and with no current treatment, prevention and palliative care the only options. TSD mice did not mimic human infantile TSD, and although mice showed some early pathology and storage of GM2 ganglioside, clinical disease would take many months to develop. The extremely mild disease in the TSD mice was likely due to a biochemical bypass, a neuraminidase. We recently demostrated that at least one of the principal murine neuraminidase, Neu3, responsible for the biochemical bypass in the catabolism of the GM2 ganglioside.Article Citation - WoS: 31Citation - Scopus: 30Absence of Pseudogap in Heavily Overdoped Bi2sr2cacu2o8+? From Tunneling Spectroscopy of Break Junctions(Institute of Physics Publishing, 2002-05) Özyüzer, Lütfi; Zasadzinski, John F.; Gray, Kenneth E.; Kendziora, Christopher A.; Miyakawa, NobuakiWe report tunneling spectroscopy of superconductor-insulator-superconductor break junctions on heavily overdoped Bi2Sr2CaCu2O8+δ with Tc = 56 K. At T ≪ Tc, the junction conductances display well-defined quasiparticle peaks at ±2Δ and in some cases a Josephson current at zero bias. Gap values as small as Δ = 10.5 meV have been observed leading to 2Δ/kTc near the BCS limit for dx2-y2 pairing. Temperature dependence of the gap magnitude, Δ(T), follows the BCS relation and both the quasiparticle gap and Josephson current vanish for T > Tc. Above Tc, the tunneling conductance shows a flat background without any indication of a pseudogap near the Fermi level.Article Citation - WoS: 19Citation - Scopus: 22Absence of Superoxide Dismutase Activity Causes Nuclear Dna Fragmentation During the Aging Process(Academic Press Inc., 2014-02) Muid, Khandaker Ashfaqul; Karakaya, Hüseyin Çaglar; Koç, AhmetSuperoxide dismutases (SOD) serve as an important antioxidant defense mechanism in aerobic organisms, and deletion of these genes shortens the replicative life span in the budding yeast Saccharomyces cerevisiae. Even though involvement of superoxide dismutase enzymes in ROS scavenging and the aging process has been studied extensively in different organisms, analyses of DNA damages has not been performed for replicatively old superoxide dismutase deficient cells. In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay. We observed that extend of DNA damage was not significantly different among the young cells of wild type, sod1Δ and sod2Δ strains. However, ccs1Δ mutants showed a 60% higher amount of DNA damage in the young stage compared to that of the wild type cells. The aging process increased the DNA damage rates 3-fold in the wild type and more than 5-fold in sod1Δ, sod2Δ, and ccs1Δ mutant cells. Furthermore, ROS levels of these strains showed a similar pattern to their DNA damage contents. Thus, our results confirm that cells accumulate DNA damages during the aging process and reveal that superoxide dismutase enzymes play a substantial role in preserving the genomic integrity in this process.
