Ph.D. Theses

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Modeling of nanoparticle-membrane interactions
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2022., 2022) Gül, Gülşah.; İleri Ercan, Nazar.
Understanding the toxicity behavior of NPs is of great importance to ensure efficient drug delivery to intracellular targets without causing cytotoxicity, to measure the long-term effects of nanoparticles (NPs), and to predict risks and hazards to humans and the environment. In this context, the current study involves (i) Coarse-grained (CG) Molecular Dynamics modeling of interactions of pristine and half polar (Janus) fullerenes with regular and peroxidized lipid membranes, (ii) cytotoxicity analysis of inorganic, organic and carbon based NPs by applying Association Rule Mining (ARM), (iii) Atomistic (AA) and CG modeling of pristine and polystyrene (PS) functionalized CNTs and their interactions with lipid bilayers. In the first part, the translocation of pure and semi-polar fullerenes along the DOPC and POPC bilayers was investigated by varying the fullerene concentration and the peroxidation level of the bilayers, and the distribution of fullerenes in the lipid bilayer was mainly explained by the degree of peroxidation and saturation level of the lipid acyl chains. In the second part, a meta-heuristic model was constructed by extracting information from the literature based on NP and cell-derived properties, as well as the conditions tested. It was determined that cytotoxicity in terms of cell viability was primarily related to the core and coating material of NPs, their synthesis pathways, and the cell type to which they were exposed. Finally, the end rings of CNT were modified at atomistic and CG level with PS and carboxyl- terminated PS (PSCOOH), which were found to be an alternative and safe material through ARM. While AA simulation results showed that PSCOOH modification was advantageous in terms of drug release, more comprehensive CG results revealed that PS chain length and grafting density should be investigated further to prevent PS blockade that may pose a threat to drug release. Increasing CNT concentration changed the structural and elastic properties of the bilayers without causing permanent membrane damage and limited the transmembrane movement of cholesterols. The penetration of the developed models to the lipid membrane occurred by non-endocytic routes.
Design of novel alkali activated materials exhibiting adsorption performance and photocatalytic activity
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2022., 2022) Kaya, Kardelen.; Uzun, Sezer Soyer.
Alkali activated materials (AAMs) are environmentally friendly alternatives to traditional cement binders with their comparable mechanical properties. Geopolymers are a subcategory of of AAMs and synthesized from aluminosilicate sources. The main motivation of this thesis is to understand the methylene blue (MB) adsorption and photocatalytic activity of AAMs and geopolymers by utilizing diffraction and microscopy techniques to establish an structure-performance relationship. Firstly, an industrial waste red mud together with metakaolin were used as raw materials and anatase amount in the geopolymer paste was varied to obtain a photocatalytically active geopolymer (RMGP) to remove MB dye from wastewaters. Findings implied that surface Ti species were responsible for the photocatalytic MB removal and 3.7 wt% addition of anatase was found to result in a tripled rate constant compared to that of pure anatase, due to synergistic effect of adsorption and photocatalysis processes. Secondly, novel and new Sep-based AAMs (Sep-AAM) as adsorbents for MB removal was introduced. Results showed that Sep-AAM has an enhanced MB adsorption capacity of 99.9 mg g-1 , adsorption occurs via chemical adsorption, and is slightly endothermic. MB adsorption performance of monolith-formed Sep-AAMs and metakaolin based counterparts (MKGP) with varying porosities were studied in the third part of this thesis. Outcomes of this part showed that it is possible to tune the MB adsorption performance and compressive strength by adjusting the porosity levels, and both of these monoliths can be regenerated up to four cycles. In the last part, MB adsorption performance of RMGP from part one was significantly enhanced by incorporating urea-based graphitic carbon nitride. The findings of this thesis demonstrate that AAMs and geopolymers with their economical and environmentally-friendly synthesis procedures offer high mechanical strength, enhanced adsorption and photocatalytic performance towards MB, and sustainable alternatives for wastewater treatment applications.
Characterization of the effect of critical design parameters on the electrochemical performance of a lithium-sulfur battery
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2022., 2022) Can, Hatice Merve.; Eroğlu Pala, Damla.
Lithium-sulfur (Li-S) batteries provides high theoretical specific energy and energy density and their performance is greatly sensitive to cell design as a result of the highly complex reaction and polysulfide shuttle mechanisms within the cathode. Electrolyte-to sulfur (E/S) ratio, carbon-to-sulfur (C/S) ratio, sulfur loading and carbon type are vital design parameters with a critical influence on the battery performance. Here, an integrated research methodology coupling experimental characterization and electrochemical modeling was applied to forecast the relation between the key design parameters and the discharge capacity, cycling performance and cell- and system-level specific energy and energy density of the Li-S battery. Firstly, the effect of the E/S ratio was examined; the highest initial discharge capacity was achieved with an E/S ratio of 20 μl mg−1, whereas, the best capacity retention was observed for 13 μl mg−1. Consequently, an E/S ratio of 13 μl mg−1 presented the best performance as the impact of the E/S ratio not only on the peak discharge capacity and capacity retention but also on cell- and system-level performance were considered. Secondly, the influence of the C/ S ratio was investigated; the Li-S cell having a C/S ratio of 2 and an E/S ratio of 13 μl mg-1 has provided the highest initial capacity in addition to the best capacity retention. Model predictions suggested that increasing the C/S ratio worsens the battery metrics at the pack level at low E/S ratios. Finally, Li-S cells with different carbon type and sulfur loading were studied. The capacity retention of Li-S cells with AB (Acetylene Black) was unaffected by the S loading, but Li-S cells with Super C65 retain capacity at higher S loadings. Li-S cells with KB (Ketjen Black) were unable to attain good performance at higher S loadings, which was surprising given their significantly larger surface area. Super C65 was projected to have the best pack performance. At medium S loadings, when discharge capacities are maximized, Li-S cells with both AB and Super C65 cathodes attain the greatest system-level metrics.
Production of Taq I restriction and modification enzymes by using two different expression systems
(Thesis (Ph.D)- Bogazici University. Institute for Graduate Studies in Science and Engineering, 2000, 2000.) Toksoy, Ebru.; Kırdar, Betül.; Önsan, Zeynep İlsen.
Taq I restriction-modification system has been cloned and expressed using two different expression systems. In the first system, Taq I restriction endonuclease was expressed as a fusion protein with the maltose-binding protein. Although the MBP-Taq I fusion protein was targeted to the periplasmic space, 80-90 per cent of Taq I endonuclease activity was found to be excreted to the growth medium without cell lysis. The fusion protein was also purified via amylose affinity chromatography from the cytoplasm, periplasm and medium of recombinant E. coli cells. Co-expression of the Taq I methylase gene improved the plasmid stability and the periplasmic and extracellular transport of the fusion protein under controlled bioreactor conditions resulting in 0.6x106 U/L extracellular Taq I endonuclease activity yield in E. coli XL1(pH185, pETMET) culture. For the second system, Taq I endonuclease gene was expressed under the control of the T7 RNA polymerase promoter. Growth and enzyme productivity of the unprotected and methylase protected E. coli cultures were analyzed under various fermentation conditions in shake flasks and bioreactor. Co-expression of the methylase gene resulted in higher enzyme production rates for longer periods yielding 250x106 U/L Taq I endonuclease activity in crude cellular extracts of E. coli BL21(DE3)[pTaqR, pMETaq] cells.
Analysis of folding kinetics for simplified model proteins
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2001., 2001.) Özkan, Ş. Banu.; Bahar, Ivet.
The conformational stochastics of simplified model chains that show an apparent two-state kinetics was explored.. A fundamental question addressed in the present analysis is to understand if the folding takes place through a continuum of paths, or if a preferred pathway involving subcooperative folding events can be discerned. To this aim, the complete sets of conformations for short model chains were generated as self-avoiding walks on a square lattice. Native-like contacts have been assigned attractive potentials, and transition rates have been assigned on the basis of native-like contacts and root-mean-square deviations between conformations. The time evolution of all conformational transitions has been analyzed starting from a uniform distribution of conformations, using a master equation formalism. A key conclusion is that: (i) The lack of intermediates that define two-state kinetics does not preclude folding through a specific sequence of events. (ii) F-value analysis, a measure of the stability and change in folding kinetics due to mutation reveals that non classical F-values can arise from parallel microscopic flow processes. Negative F values result when a mutation destabilizes a slow flow channel, causing an overflow into a faster flow channel. F-values greater than one occur when mutations redirect a fast flow into a slower channel.
Fermentation and recovery of EcoRI endonuclease using two different genetically engineered E.coli strains
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 1997., 1997.) Yıldır (Tamerler), Candan.; Kırdar, Betül.; Önsan, Zeynep İlsen.
A small scale procedure developed for the purification of EcoRI restriction enzyme has been applied to two different overproducing E.coli strains. The final purification yields obtained are 1.3x105 U/g cells for E.coli M5248 and 3.3x106 U6g cells for E.coli 294. For the E.coli 294 (pPG430) strain, 0.1 mM IPTG concentration at an optical density of 1.2 at 595 nm over an 6 hours period were determined to be the optimum conditions for induction. For the E.coli M5248 (pSCC2) strain, the induction of EcoRI enzyme was achieved by a temeparuter-shift at an optical density of 1.0 at 590 nm over an 5 hours period. Investigation of the stabiltiy of both recombinant plasmids showed that the enzyme productivity and the plasmid stabilty were effected fro the medium composition and the temperature increase.The unstructured modeling of cell growth has shown that substrate-inhibited kinetics is successful in predicting the growth behavior of both E.coli strains. A three-compartment model was developed to describe the dynamic changes in the intracellular components of E.coli 294 cells. The model gives a good description of the growth kinetics with an initial glucose concentraiton of 10 g/L.
Fermentation characteristics of four genetically engineered Saccharomyces cerevisiae strains
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 1997., 1997.) Birol (Deniz), Gülnur.; Önsan, Zeynep İlsen.; Kırdar, Betül.
The production of ethanol from starch has been investigated in four genetically modified Saccharomyces cerevisiae strains (YPG/AB, YA7, YPG/MM and YPB-G). Three of the four strains produce the Aspergillus awamori glucoamylase together with either the Bacillus subttilis (YPG/AB, YA7) or the mouse (YPG/MM) á-amylase as separately secreted polypeptides. YPB-G, on the other hand, secretes a bifunctional fusion protein that contains both the B.subtilis á,amylase and the A.awamori glucoamylase activities. Substrate utilisation, biomass growth, ethanol production and plasmid stability were all studied in both starch and glucose-containing media in shake flasks and in a New Brunswick fermenter. Much higher growth rates were found any of the four strains was grown on glucose. YPG/AB showed the most efficient utilisation of starch for ethanol production with the lowest levels of reducing sugars accumulating in the medium. This strain produced 18.8 g/L and 43.8 g/L ethanol from 50 g/L and 100 g/L starch respectively. The superior performance of YPG/AB and YA7 as compared to YPB-G was found to correlate with its higher level of á -amylase activity in starch containing media. YPB-G, which secretes the bifunctional fusion protein, could produce 35.2 g/L ethanol in media with starch concentrations above 100 g/L, while YPG/MM did not produce ethanol from starch because of its negligible secretion of glucoamylase. Furthermore, a simple structured mathematical model was proposed to analyze the growth and enzyme secretion kinetics of the recombinant strain (YPB-G) in a complex medium containing glucose. The parameters obtained by the nonlinear estimation techniques were validated against experiments that were not used in the calibration of the models.
A process for the deterpenation of essential oils by extraction/adsorption/desorption using supercritical carbon dioxide
(Thesis (Ph.D.)- Bogazici University. Institute for Graduate Studies in Science and Engineering, 1999., 1999.) Eskinazi, Orli A.; Hortaçsu, Öner.; Akman, Şükrü Uğur.
The main purpose of this study was to establish a supercritical-fluid-aided process in order to enhance the quality of essential-oils products through the removal of the monoterpene (MT) hydrocarbons. The example oil chosen for this study among the hundreds of essential oils is origanum oil (Origanum Munituflorum). A new process arrangement constituted by a dense-CO2 extraction coupled with continuous adsorption/desorption process has been developed, and is suggested for the fractionation and successful deterpenation of this essential oil. During the different forms of operations and procedures implemented, the non-monoterpene (NMT) cut having the essential odor and properties of the origanum oil, was intended to be separated from the unstable MT fraction of the oil. Based on the experimental results, enhanced fractionation of the oil is obtained via adsorption on activated carbon at 40C/7.5 MPa and desorption at 40C with step-wise pressure increase method: first at 8.0 MPa to recover the MT components and then, at 14.5 MPa to collect the NMT constituents. This process scheme, in which the mixing cell situated before the adsorber acts as a phase separation chamber, is more successful in deterpenating origanum oil since the mixing cell adds an extra degree of flexibility to the system through providing an additional separation between the MT and NMT hydrocarbons. Furthermore, compared to silanized silica gel, activated carbon was found to be a more promising adsorbent in fractionating and producing an origanum-oil product almost free of its MT constituents.
Dynamics of rising bubbles and stress measurements through birefringence in viscoelastic liquids
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2021., 2021.) Eribol, Pınar.; Uğuz, Abdullah Kerem.
Bubble dynamics in a viscoelastic liquid are studied to check the existence of a discontinuity in the terminal velocity that occurs at some critical bubble volume and cusp formation at the bubble tail and their relation with the stress around the bub ble, which is measured through flow birefringence. A wide range of bubble volumes, 5-2000 mm3 in 0.10-0.40 wt% polyacrylamide (PAAM) solutions is employed. The terminal velocity decreases with PAAM concentration and increases with bubble vol ume but plateaus. The plateau velocity is independent of PAAM concentration. No discontinuity in the terminal velocity is observed, which is supported by the bubble shape parameters of which circularity, the minor axis, and eccentricities are found to be concentration-dependent. Increasing the bubble volume changes the shape from spher ical to prolate, teardrop with a cusp and cap-shapes. The critical bubble volume for the cusp formation is independent of the PAAM concentration. With the addition of 100 ppm surfactant SDS leads less distortion of the bubbles and cusp formation at smaller volumes. Large bubbles and dilute solutions cause bubbles wobbling. Increasing the PAAM and the surfactant concentrations shows an increase in the lateral direction motion. The retardance and the stretching angle around the bubble are measured for PAAM and hydroxypropyl cellulose (HPC) solution. For small bubbles, the stress is proportional to the concentration; whereas for large ones, bubble shapes become im portant for the stress. No significant effect of the temperature gradient on the bubble dynamics is observed. Weak convection patterns are seen through Schlieren method.
Photocatalytic hydrogen production over ionic liquid coated semiconductors
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2021., 2021.) Can, Elif.; Yıldırım, Ramazan,
The objective of this thesis is to develop active and stable dye sensitized and ionic liquid (IL) encapsulated photocatalysts for hydrogen production, and to investigate the roles of photocatalysts constituents on hydrogen production rate. First, comprehensive experimental datasets for photocatalytic (PWS) and photoelectrochemical (PECWS) water splitting were constructed from literature while a large dataset for water solubility in ILs were created computationally using DFT and COSMO-RS. Then, these datasets were analyzed by machine learning (ML); association rule mining (ARM), decision tree (DT), random forest (RF) and deep learning (DL) were implemented in R and Python environment. In PWS analysis, the clear trends and the high fitness of the models constructed, especially those involved the band gap, indicates that PWS over perovskites is predictable but the sound solutions like ion doping, use of co-catalyst, or use of sacrificial donors did not help as much as desired. The prediction accuracies of DL and classification accuracy of DT models for the water solubility in ILs were also high, and the properties of anionic parts of ILs are more influential for water solubility. The band gap of semiconductors used in PECWS were also predicted successfully even though the prediction accuracy of photocurrent density was not satisfactory. In the experimental part of the thesis, the enhancement of photocatalytic hydrogen production over 1 wt% Pt/TiO2 sensitized by N719 dye and coated by a thin layer of ionic liquid ([BMIM][BF4]) has been investigated; SEM-EDAX, CTEM, FTIR, XRD, and UV-Vis characterization of the photocatalysts, and electrochemical analysis of the respective photoelectrodes were performed. The IL coating increased the performance of 1%Pt/TiO2 by providing better charge transfer between the photocatalyst and the aqueous reaction medium while simultaneously preventing the recombination of photogenerated electron-hole pairs; the improvement was much higher with the use of IL and N719 together. The performance of 1% Pt/SrTiO3 was also tested but the reproducible results could not be obtained. Finally, the factors related to the structure of the reactor and operational conditions (like dead volume, gas-liquid interfacial area, sweep gas flowrate and stirring speed) were also found to be influential over the hydrogen production rate.
A study on co-free hydrogen production from hydrocarbons and COx elimination through pre-combustion
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2020., 2020.) Eropak, Belkız Merve.; Aksoylu, Ahmet Erhan.
The goal of this research study is to design and develop active, stable and selective alkali promoted Pt-based catalysts and activated carbon-based adsorbents for COx elimination to be used in CO-free hydrogen production and CO2 removal. Firstly, Pt-Re-Na/CeO2 and Pt-Re-Na/TiO2 catalysts were designed and prepared for WGS reaction. The effect of Na loading, support type, reaction temperature, feed type and composition (H2O/CO ratio) on WGS performance were considered as the experimental parameters. Among the prepared catalysts, sequentially impregnated 1%Pt-1%Re-2%Na/CeO2 exhibited the highest performance under Realistic Feed with H2O/CO=6.7. Serial OSR-WGS tests were also conducted for two OSR feed compositions having different O/C ratio and the highest real WGS activity was achieved over sequentially impregnated 1%Pt-1%Re-1%Na/CeO2 at 350°C as 43.0% CO conversion. The freshly reduced and spent forms of the catalyst samples were characterized by SEM, XPS, XRD and Raman spectroscopy. Combined evaluation of the Na1s and Ce3d spectra of the highly active catalysts, suggests the NaOx species should be more influential than CeOx species in the WGS reaction mechanisms. Surface formate and carbonate species under reaction conditions were examined in operando FTIR-DRIFTs-MS tests over Pt-Re-Na/CeO2 catalysts. The combined evaluation of WGS performance and OSC results indicated that structural OSC (S-OSC) and effective OSC (E-OSC) have both significant effect on WGS performance. E-OSC values of the catalysts were found in direct accordance with their performance results. In the adsorbent design part, CO2 and CH4 adsorption capacities of AC-based NaOH impregnated samples were determined for various “temperature-pressure range” couples, their selective adsorption capacities were measured under CO2-CH4 gas mixtures through using a novel methodology developed by our group, and the adsorption on the samples was modelled. The best performing adsorbent in terms of selective CO2 adsorption under CO2:CH4=1:1 and 1:9 was determined as AC6-200, which is the air oxidized AC doped with Na.
Development of microfluidic platforms for therapeutic purposes
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2021., 2021.) Gençtürk, Elif.; Ülgen, Kutlu Ö.; Mutlu, Şenol.
This thesis describes the present state of the development and applications of microfluidic systems used in cell biology and analyses of experiments conducted with in house fabricated thermoplastic based microfluidic devices. COP based microbioreactors are produced by hot embossing and thermocompression bonding methods. Yeast and mammalian (THP-1) cells are employed in microfluidic experiments where RFP:Nop56 protein is used to track changes in cell cycle as well as protein synthesis within the yeast cells and GFP:ASC gene with a role in apoptosis is used to track the drug effects on THP-1 cells. HU, metformin, temsirolimus and HMF are administered to yeast cells and their response to these drugs are investigated. By computational systems biology approach, a genome-scale metabolic model specific to the yeast is reconstructed, and the inhibitory effect of HMF on growth and ethanol production is elaborated by estimating the internal flux distribution within the yeast metabolic network. To develop putative treatment strategies towards cancer, the COP based microbioreactor is integrated with Cr/Au interdigitated electrodes to test TTFields. In the high electrical field experiment, the yeast cells go through electroporation and in the low electrical field experiment, the cells have prolonged mitosis. Furthermore, human monocytic leukemia cell line THP-1 cells are tested in two-phase microfluidic devices, where cells are confined to droplets with several inhibitors/drugs. An increase in the fluorescence intensity of the ASC gene responsible for apoptosis is observed in cells under the influence of drugs. An important conclusion of this thesis is that these microfluidic platforms can be successfully used for studying the drug effects on tumors, observe cell to cell heterogeneity and may shed light on the putative treatment strategies towards cancer. These microbioreactors are still open for research and development, and solutions need to be found for each case separately.
Systems-level understanding of copper effect in Saccharomyces cerevisiae
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2019., 2019.) Öç, Şebnem.; Haliloğlu, Türkan.; Kırdar, Betül.
Copper is a crucial trace element for all living systems as it is required for the proper functioning of several biological processes. Copper homeostasis, which governs the mechanisms of copper uptake, delivery, utilization, and export, is impaired in a variety of human diseases which underscores the importance of the balancing of the intracellular copper levels. High similarity of the copper homeostatic systems in yeasts and humans makes Saccharomyces cerevisiae an ideal eukaryotic model organism for the studies related to copper transport. In this thesis, the effect of copper on yeast cells was investigated through integrative systems biology approaches. The dynamic transcriptomic response of the mutant cells lacking the copper transporter gene CCC2 as well as HO deleted cells, as reference, were evaluated based on the transcriptional changes in genome scale. Considering the fact that perturbation response experiments enables understanding of the dynamic changes as well as response mechanisms within the cells, copper impulse experiments were performed in order to investigate the copper effect. The strains were grown in chemostat cultures under copper deficient conditions, and copper is introduced into the media in excess amount which is not toxic. The investigation of the dynamic transcriptional profiles of the strains gave insight into the alterations in various biological processes including stress response, sulfur compound metabolism, DNA repair, and respiratory complex biogenesis as well as copper and iron homeostasis, in response to copper which differed between the strains especially as of the fifth minute. The identification of the significantly correlated paths within the reconstructed copper sensing network indicated possible involvement of several proteins in copper sensing and/or transport, and also indicated that copper homeostasis is controlled in mRNA level, and mRNA decay pathways may have central role in this regulation.
Knowledge extraction for organometallic perovskite solar cells from published data in literature
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2019., 2019.) Odabaşı, Çağla.; Yıldırım, Ramazan,
Orgonolead halide perovskite solar cells (PSCs) have been attracted great attention in recent years. This rapid progress is due to excellent light absorption and charge-carrier mobilities of the perovskite materials besides its low-cost and easy processing conditions. In addition to high power conversion efficiency (PCE), reproducibility, hysteresis and longterm stability of perovskite solar cells are major factors to be solved before commercialization of this technology . The objective of this dissertation is to extract useful knowledge from literature to improve the overall performance of this technology for commercialization. The extensive datasets for PCE, reproducibility, hysteresis and longterm stability of PSCs were constructed from the published papers in literature and analyzed using machine-learning tools to determine the effects of materials and perovskite deposition methods employed during cell manufacturing. The evolution of PCE with time was statistically analyzed under different circumstances (i.e. using different materials types or perovskite deposition methods). Then, the databases for PCE, hysteresis and long-term stability were modeled using random forest, association rule mining and decision tree methods to detect the most effective variables and combinations leading to high performance. For reproducibility, pooled variances of different factors were calculated and compared. The mixed cation perovskites, doped mesoporous TiO2 (second electron transfer layer) and LiTFSI+TBP+FK209 (additive to hole transfer materials) were found to promote high efficiency, reproducibility and stability while they lowered the hysteresis; SnO2 (compact ETL), DMF+DMSO (solvent) and diethyl ether (anti-solvent) also had positive effects on these cell characteristics except hysteresis. Hence, it was concluded that the common factors which leaded high PCE, also leaded high reproducibility, low hysteresis and long-term stability. Additionally, our findings were in a reasonable aggrement with the literature showing that the data mining and statistics can be used effectively to derive general results and detect trends, which can not be seen by naked eyes.
CO2 reforming of CH4 over structured Ni-based catalysts
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2017., 2017.) Leba, Aybüke.; Yıldırım, Ramazan,
The aim of this study was to contribute to the development of an economical CDRM process requiring less amount of energy and utilizing cheaper, more active and more stable catalyst. For this purpose, the photocatalytic assistance in CDRM process over Ni-Co impregnated MgO, ZnO and TiO2 were tested first at 0-500 °C under UV and visible light in a photocatalytic reaction system. However, no considerable CH4 or CO2 conversion was obtained even if TiO2 photocatalyst was tried to be improved by the addition of dye or organolead perovskite sensitizers to increase its visible light sensitivity. The study was proceeded with the use of various structured Ni-based catalysts such as wash-coated MgO, CeO2 or SiO2 over monoliths, NixCo3-xO4 nanowires and Ni-based nanorods due to their low pressure drop and high surface area. The performance tests of structured Ni-based catalysts were done at a temperature range from 600 °C to 900 °C with various gas hourly space velocities (GHSV) and CH4/CO2 ratios. SEM-EDX, XRD and XPS studies were also performed to understand the surface morphology of the catalysts. The results showed that 8wt.%Ni-2wt.%Co over MgO wash-coated monolith structure led to higher CH4 and CO2 conversions as well as closer H2/CO product ratio to one compared to particulate MgO catalysts and CeO2 or SiO2 wash-coated monoliths. SEM-EDX and XPS results of 8wt.%Ni- 2wt.%Co over MgO wash-coated monolith catalyst spent at 750 °C also showed considerable amount of coke formation; however, the use of 3% oxygen in the feed suppressed the coke formation significantly. The catalyst was stable for 48 h in the presence of O2 added feed (3%) over 42000 mlgcat -1h-1 at CH4/CO2 feed ratio of one and 750 °C. NixCo3-xO4 nanowire structures also showed high catalytic activity at the same conditions; however, they were not stable even under the O2 added feed. The addition of Pd to this catalyst did not improve its stability either. The performance test of Ni-based MgO nanorods and their coated form over monolith was also tested. Although they resulted lower catalytic activity than Ni-based MgO wash-coated monolith, they seemed to be more resistant to coke formation as the SEM analysis indicated.
Peptide drugs against antibiotic resistant bacteria
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2017., 2017.) Alaybeyoğlu, Begüm.; Özkırımlı, Elif.
Membrane active peptides have found great interest as drug candidates due to their unique mode of action and availability in nature. In the past 20 years, beta lactamase-mediated antibiotic resistance has become a lethal issue with the widespread of antibiotic cleaving beta-lactamase enzyme due to the misuse of beta-lactam type antibiotics. In this context, antimicrobial peptides are promising broad-spectrum al ternatives to conventional antibiotics in the era of evolving bacterial resistance. In an eﬀort to propose peptide drugs against antibiotic resistance, the understanding of how peptide drugs take action is essential. Here, the goal was to propose novel peptide an timicrobials that can eﬃciently inhibit periplasmic beta-lactamase and internalize into bacteria. For this aim, the cell-penetrating peptide pVEC and its ﬁrst ﬁve residues (LLIIL) deleted variant del5 pVEC, were analyzed using molecular dynamics simula tions to gain insights about the mechanism and free energy of the lipid bilayer translo cation, and the contribution of the LLIIL residues to this peptide’s uptake. Motivated by the pVEC sequence and the studies on pVEC emphasizing the importance of its LLIIL residues to the uptake of the peptide, the approach was to build chimeric se quences, by combining the LLIIL residues of pVEC with the beta-lactamase inhibitory peptides to facilitate their uptake. Our results show that the addition of LLIIL to the beta-lactamase inhibitory peptides increase their membrane permeabilizing potential. Interestingly, the addition of this short stretch of hydrophobic residues also modiﬁed the inhibitory peptides such that they acquired antimicrobial property. The results suggest that addition of the hydrophobic LLIIL residues to the peptide N-terminus may oﬀer a promising strategy to design novel antimicrobial peptides in the battle against antibiotic resistance.
Computational and experimental investigations into the mechanism of functional motion in biomolecular systems
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2016., 2016.) Fas, Ayşe Burcu Aykaç.; Haliloğlu, Türkan.
The seemingly random fluctuations that proteins exhibit in their native states actually harbor major contributions from the global/cooperative motions they undergo during functional transitions. Computationally efficient, robust approaches like elastic network models (ENM) that exploit the intrinsic dynamics of proteins are of great value in building up hybrid approaches bridging experimental and computational studies and extending each application's range. ENM global modes show functional significance and compares well with functional conformational changes. The purpose of this study is to build upon currently available computational techniques that generate transition pathways connecting end states. In this thesis, a practical hybrid approach, anisotropic network model (ANM) guided Langevin dynamics (LD) simulations (ANM-LD) has been developed, where the dominant ANM low-frequency modes are utilized to drive LD simulations. In ANM-LD, the initial conformation is moved along the selected ANM mode at each cycle, taking advantage of the evaluation of the interactions and energetics of the system via short cycles of all-atom implicit LD simulations. A detailed assessment of the method, in terms of creating physically meaningful pathways and approaching the final state, are carried out for a set of proteins. As exemplary cases, the analysis and results for adenylate kinase and maltose transporter is presented. ANM-LD was also applied to heat shock protein 90 (Hsp90) in apo, ATP-bound and Geldanamycin (GDM)-bound states, the latter combined with AFM experiments, to study the effect of temperature on the Hsp90-GDM binding dynamics. Lastly, conventional molecular dynamics simulations, ENM and ANM-LD are utilized to investigate CRP dynamics.
Optimal resilient retrofit design of heat-exchanger networks
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 1996., 1996.) Konukman, Alp Er Şevki.; Akman, Şükrü Uğur.; Çamurdan, Mehmet Cihan.
A new index, called Design Resiliency Index, which numerically indicates the size of feasible region in terms of uncertain source-temperature or flowrates for the fixed design parameters of a network structure, is proposed. A new retrofit design approach for given HEN structures, towards resilient and controllable designs at minimum cost is also proposed. The task of designing a heat-exchanger network for a pre-determined structure (retrofit design), which is not only economically at minimum cost but also has the ability to reject the disturbances predefined for all possible source-streams and in all directions (increasing or decreasing), is introduced as a single nonlinear programming problem. The objective of this constrained nonlinear optimization problem is to find the individual exchanger areas and nominal utility consumptions which minimize the total annualized cost of the given HEN structure and, at the same time, to satisfy the target-temperature constraints for set of disturbances predefined in all possible directions. For the definition of the expected disturbances for all possible directions in source-streams, a new index is also proposed, Retrofit Design Resiliency Index, to be used in the formulation. It is shown that designing a control system using conventional approaches which offers the placement of control variables after the design stage, not only limits the resiliency hence the controllability range of a HEN, but also could be more expensive than the solutions generated by the method proposed in this study.
Elastic network model based approaches for conformer generation and docking applications
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2015., 2015.) Soner, Zeynep Kürkçuoğlu.; Turgut, Pemra Doruker.
The dynamic nature of proteins poses challenging problems in computational biology, especially in terms of conformational sampling and transitions. In this thesis, an Elastic Network Model (ENM)-based computational method, namely ClustENM, was developed for sampling large conformational changes of biomolecules with various sizes and oligomerization states. ClustENM is an iterative method that combines ENM with energy minimization and clustering steps. It is an unbiased technique, which necessitates only an initial structure of the biomolecule as input but no information on target. To test the performance of ClustENM in conformational sampling, it was applied to six systems, namely adenylate kinase (AK), calmodulin, p38 MAP kinase, HIV-1 reverse transcriptase, triosephosphate isomerase (TIM), and supramolecule 70S ribosome. The generated atomistic conformers were found to be in agreement with experimental data (971 structures) and molecular dynamics (MD) simulations. ClustENM was used to model the trigger factor-50S subunit of ribosome complex, leading to structures consistent with the data from cryo-EM. Additionally, ligand e ects on TIM conformational dynamics were investigated based on MD simulations of its apo form and complexes with an inhibitor or its substrate. Generated conformers from ClustENM were further used in docking applications for AK, LAO-binding protein, dipeptide binding protein and biotin carboxylase. Close-to-native ligand binding poses were obtained especially in the rst three cases. Thus, ClustENM emerges as a computationally e cient method applicable to extremely large systems or transitions. Its utility relies on the generation of a manageable number of atomistic conformers that are entropically accessible to a folded starting structure, which can also assist ligand docking applications.
Network topology and dynamic data analysis in saccharomyces cerevisiae
(Thesis (Ph.D.) - Bogazici University. Institute for Graduate Studies in Science and Engineering, 2016., 2016.) Karabekmez, Muhammed Erkan.; Kırdar, Betül.
Biological systems which can be represented as networks and graphs are highly dynamic and responsive to environmental and genetic perturbations in a time dependent manner. These networks are hierarchically organized and consist of tightly clustered groups of proteins that work together as part of a biological process or a complex to achieve a specific function in a cell. With the emergence of high-troughput dynamic datasets, dynamic data analysis became a challenge in systems biology with the other challenges such as representation of biological systems as networks and elucidation of graph properties of these networks biologically and integration of multi –omics datasets in order to extract biologically meaningful results. The aim of this thesis is to develop a novel metric of centrality to identify biologically important nodes and to develop novel approaches to investigate dynamic datasets. In the first part, a novel global metric of centrality, weighted sum of loads eigenvector centrality (WSL-EC), counting all eigenvectors was proposed to identify essential and biologically central nodes. WSL-EC was found to outperform in capturing biologically central nodes, such as pathogen-interacting, HIV-1, cancer, ageing, and disease-related genes and genes involved in immune system process and related to autoimmune diseases in the human interactome compared with other metrics of centrality. In the second part dynamic transcriptional response of S. cerevisiae cells to doxorubicin, which is used as chemotherapeutic reagent in the treatment of different types of cancer, was monitored by quantification of RNA transcripts in cells which were grown in a chemostat fermenter, through microarray technology. Resulting dynamic transcriptome data were investigated by using different approaches and integrating interactome and regulome. The clustering and analysis of the transcriptomic response of S. cerevisiae cells to doxorubicin indicated that the genes involved in DNA replication, mismatched repair, cell cycle and base excision repair pathways were affected and several transcriptional factors were identified. In the third part the data collected from literature related to the transcriptional response of yeast cells to DNA damage was similarly investigated and compared with the response to doxorubicin.

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