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Kaspaz-1 için peptit bazlı ilaç tasarımı ve metabolik yol analizi
As one of the mostly studied protein in the literature, caspase-1 (ICE) attracts the attention of many scientists due to its crucial roles in inflammatory responses. It has other roles in the apoptotic path, for example, because of having more than 40 substrates. Increased expression of its substrates such as pro-IL-1beta results in inflammatory disorders. Consequently, inhibition and pathway studies related to caspase-1 have gained importance.Peptide based drug design for caspase-1 is performed and potent inhibitors are determined computationally. Bicylic (a molecule that contains two fused rings) and ketone structures with Asp and D-enantiomeric aminoacids are obtained as good inhibitors in accordance with previous experimental work. Moreover, multi-target drug determination in the caspase-1 pathway is made. Conformational factors in tripeptides are also taken into consideration with Viterbi Algorithm, which indicates whether a peptide can change its conformation from minimized state to bound state.Knockout analysis on the ICE pathway by Gaussian Network Model (GNM) shows knockouts of NLRP3, ASC, caspase-1, NF-kappaB, pro-IL-33, TLR4, TLR2, TRIF and MyD88 are effective.?
Silika aerojel polimer kompozitlerinin hazırlanması ve karakterize edilmesi
In this study, new nanotechnology-based high performance insulation systems for energy efficiency, nanostructured composites of silica aerogels with polymers are being developed as core materials for vacuum insulation panels in buildings. Monolithic composites of a wide variety of polymers with silica aerogels were synthesized by modification of the conventional sol-gel method to produce silica aerogels. The polymers used in the study are poly(ethylene block poly ethylene glycol) (PEPEG), poly(vinyl pyrrolidone) (PVP), poly(vinyl acetate) (PVAc) and poly(methyl vinyl ether) (PMVE). Characterization of the composite materials was performed by Fourier Transform Infrared - Attenuated Total Reflectance (FTIR-ATR) spectroscopy, Thermal Gravimetric Analysis (TGA) and by Nitrogen Physisorption using BET. Both transparent and opaque crack-free monolithic composites suitable for testing and use in VIPs were obtained. The presence of polymer in the composites was confirmed by IR spectroscopy and TGA. The composites were mesoporous materials with high surface areas around 800 m2/g and average pore sizes around 5 nm. Incorporation of polymers did not significantly change the pore size distribution and the specific surface area of the pure silica aerogels. The effects of the time of polymer addition at various stages of the conventional sol-gel process such as before/after the hydrolysis step and during the aging step, on the properties of the composites were investigated. Opacity was found to be correlated to the phase separation of the polymer from the reaction mixture. The effect of polymer content on the resulting properties was also investigated along with density, porosity and shrinkage calculations.
T-hücresi akut lenfoblastik lösemi için birbirine bağlı marker tanımlanması
T-cell acute lymphoblastic leukemia (T-ALL) is a very complex disease, resulting from proliferation of differentially arrested immature T-cells. The molecular mechanisms and the genes involved in the cause of T-ALL remain largely undefined. In this study, we found biomarkers to differentiate individuals with T-ALL from the non-leukemia/healthy ones, to discover markers that are not differential themselves but interconnect with highly differentially expressed genes, and to have a network-based view of T-ALL. Instead of applying only expression-based differential gene analysis and obtaining hundreds of candidate disease-causing genes, we integrated gene expression data of T-ALL and healthy samples with the human protein-protein interaction data in order to discover diagnostic biomarkers not as individual genes but as subnetworks. By using a network-based approach, we have identified 19 significant subnetworks, containing 102 genes (out of 409 genes). A given subnetwork contains up-to 12 genes. The classification/prediction accuracies of subnetworks are considerably high, as high as 98%. Some genes in the subnetworks were already known to be associated with T-ALL, but we found new ones to be involved in T-ALL development. The subnetworks were rich in transcription factors whose ectopic activation is known to be one of the reasons behind T-ALL. The Zinc-binding proteins are also abundant in subnetworks. Zinc levels are low in ALL-patients. Zinc supplement given to a T-ALL patient may increase the efficiency of chemotherapy. We recovered 6 tyrosine kinases which have important roles in T-cell survival, proliferation, and immune response. These important genes in our subnetworks may serve as an alternative to the traditional biomarkers used for the diagnosis of T-ALL. The aim of this study is also to help investigators to highlight potential disease gene candidates for further experimental validation.We also applied a typical hierarchical clustering method to most differential 100 and 200 genes between T-ALL and healthy samples. As opposed to the presumption that most differential 100 or 200 genes would classify the diseased samples better, our subnetworks achieved the same or, in some cases, higher classification accuracies. Doing the same/better job with 10 genes in a subnetwork, instead of 100 or 200 genes might be regarded as an accomplishment. In short, network-based classification techniques help us to identify biologically more meaningful subnetworks than expression-based techniques which return thousands of differential genes.
DNA tamirinin yüzey plazmon rezonansı ile gerçek zamanlı incelenmesi
DNA structure can be greatly affected by UV light exposure. The cyclobutane prymidine dimer (CPD) and 6-4 lesion formations along with the specific breaks on strands are the most common type of DNA damage caused by UV irradiation. Specific to UV-damaged DNA, CPD photolyase I and II construct two subfamilies of flavoproteins, and they have recognition and repair capabilities of CPD sites on both single stranded (ssDNA) and double stranded (dsDNA) DNA with the aid of blue light energy. The other types of flavoprotein family consist of cryptochromes (CRY), and the most commonly known types act as photoreceptors in plants, or circadian rhythm regulators in animals, but lack photorepair activity. Recently, it has been found that a specific type of cryptochrome also has photorepair activity on ssDNA. This protein, called cryptochrome-DASH (CRY-DASH), is yet to be studied for its binding to DNA with newly developed techniques. In this thesis, CRY-DASH-DNA interaction was investigated using Surface Plasmon Resonance (SPR) which is a common assay to characterize protein-DNA or protein-protein interactions. Next, interaction of UV damaged and undamaged DNA with CPD photolyase was then examined and compared with the interaction of damaged/undamaged DNA and CRY-DASH. SPR shows the immediate molecular binding of DNA to the surface and confirms the specific binding of photolyase and CRY-DASH with UV treated or UV untreated DNA by providing kinetic constants of binding. This study is significant for investigation of repair of lesions in the DNA structure using SPR.
Patates ADP glikoz pirofosforilaz enziminin allosterik özelliklerinin modulasyonu için önemli amino asitlerin belirlenmesi
ADP glucose pyrophosphorylase (AGPase) is a key regulatory enzyme of bacterial glycogen and plant starch synthesis as it controls carbon flux via its allosteric regulatory behavior. Whereas the bacterial enzyme is composed of a single subunit type, the plant AGPase is a heterotetrameric enzyme (?2ß2) with distinct roles for each of the two subunit types. The large subunit (LS) is involved mainly in allosteric regulation through its interaction with the catalytic small subunit (SS). Previously, critical amino acids of potato (Solanum tuberosum L.) LS that interact with SS in the native heterotetramer structure were identified both computationally and experimentally. In this study, we aimed to improve the heterotetrameric assembly of potato AGPase and to detect residues located on the interface involving the allosteric regulation of the enzyme with a reverse genetics approach. A mutant, ?2ß2 formation deficient, large subunit of potato AGPase named LSR88A was subjected to random mutagenesis using error prone PCR and screened for the capacity to form an enzyme restoring glycogen production in glgC- Escherichia coli, AGPase activity deficient, containing wild type SS by assessing iodine staining. Fifteen suppressor mutants were identified and sequence analysis of these mutants revealed that mutations are mainly clustered at subunit interface and nearby the subunit interface. Subsequently, R88A mutation was reversed with site directed mutagenesis to see the effect of these mutations in the absence of R88A mutation. Kinetic characterization showed that two random mutants, named RM2 and RM10, exhibit altered allosteric properties than the wild type. These results indicate that interfaces between the large and small subunits are significant for the allosteric properties of the AGPase. Obtaining stable and up-regulated AGPase variants will enable us to use these mutants to increase the starch yield in crop plants.
Küçük molekül ağırlıklı ilaçların proteinler ile etkileşimlerinin teorik ve deneysel olarak incelenmesi
In this study, interaction of small molecular weight drug compounds with proteins has been characterized. The binding constants of interactions were first theoretically calculated using molecular docking simulations. Next, these interactions were experimentally investigated via Surface Plasmon Resonance (SPR). The theoretical binding constants, KD, predicted from theoretical calculations have been compared with the experimental values obtained from SPR. As a model protein, Escherichia coli (E.coli) DNA photolyase was used due to its known crystal structure. Among the eight drugs analyzed, theoretical and experimental values have shown similar binding affinities between selected drug and protein pairs. The results obtained in this study may be significant to characterize the unknown interactions of existing drugs with various proteins.
İnterlökin 1 beta (IL-1ß) için peptid kökenli inhibitör dizaynı
Interleukin 1 beta (IL-1ß) is a pro-inflammatory cytokine which is activated intracellularly by the cleavage of Caspase-1 (Interleukin converting enzyme, ICE). Upon activation, IL-1ß is secreted to the extracellular region. Increased expression of IL-1ß is associated with several diseases such as rheumatoid arthritis and intestinal inflammation. Thus in controlling these kinds of diseases, blocking IL-1ß has great importance. IL-1ß has an embedded receptor (IL-1R) and an accessory protein (IL-1RAcP) in the cell surface. IL-1ß binds to its receptor and to the accessory protein which juxtaposes the intracellular domains of its receptors and causes more expression of IL-1ß. In this study, inhibition of active IL-1ß has been studied extensively by using computational docking tools and techniques. Binding residues of IL-1ß to its receptor were accepted as docking regions. Genetic Algorithm (GA) and Viterbi algorithm (VA) based on the Hidden Markov Model were applied to obtain the most suitable inhibitor candidate by considering its binding free energy and secondary structure conformation. As a result, tripeptide and pentapeptide candidates from Genetic Algorithm and thirty heptapeptide candidates from the Viterbi Algorithm were obtained. Elimination of the candidates was achieved by Molecular Dynamics Simulations by calculating binding free energies of the ligands. Most potent inhibitor for IL-1ß was observed to inhibit IL-1? as well. The unbinding process of ligands was investigated and their probability distribution graphs were examined.
Endüstriyel bir hidrokraker reaktörünün modellenmesi
The aim of this study is to model an industrial hydrocracker reactor. As preliminary work, the industrial hydrocracker reactor was simulated by the Aspen HYSYS Hydrocracker. Next, a first principle model was developed in which the discrete lumping approach was adopted. Since the model consists of a set of ordinary differential equations and algebraic equations which have to be solved simultaneously, a code was written by using MATLAB. Parameter estimation was performed to match model predictions with real plant data. Under constant conversion operating conditions model estimates matched the plant data closely. In order to investigate the effect of catalyst deactivation on parameters, the constant-conversion model was updated using data corresponding to operating days with different catalyst activity. While significant changes in the product distribution parameters and heat of reaction parameters were not observed, rate constant parameters correlated well with catalyst deactivation. Since the reactor inlet temperatures are the major independent and adjustable process variables, their effect on plant products and conversion was also studied. For the constant conversion training data, the model showed low sensitivity of conversion to reactor inlet temperatures. Next, a new model was developed by estimating the parameters using operating data at two different conversion levels. Simulations showed that an overall 3.1 °C increase in inlet temperatures along the reactor affected the conversion by 0.75 % which is a remarkable value for an Hydrocracker unit. Finally, the predictive ability of the model was questioned by analyzing the plant data. It was observed that increase in inlet temperatures resulted in the same conversion for some days of operation. This means that in order to keep conversion constant the reactor inlet temperatures are adjusted by the existing advanced control system to reject disturbances such as feed properties, catalyst deactivation or other operation conditions. The developed model cannot predict such changes. However its parameters can be updated on-line to match different plant data that includes disturbance effects. Alternatively, a fundamental or empirical disturbance model can be integrated into the developed model in order to predict the behavior of the process under realistic disturbances.
Structural and functional analysis of perforin mutations in association with clinical data of familial hemophagocytic lymphohistiocytosis type 2 (FHL2) patients
The immune system is the defense mechanism of the body against pathogenic agents and tumor cells. Perforin, a multi-domain pore-forming protein, plays a key role in the immune system as a cytotoxic effector molecule secreted by T-lymphocytes and Natural killer (NK) cells within granules, which also contain granzyme B that induces apoptosis. In synergy with granzyme B, perforin acts via pore formation at the cell membrane of virus-infected and transformed cells that are targeted to be eliminated. A vast number of observed mutations in perforin impairs this mechanism resulting in a rare but fatal disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL2). FHL2 is an autosomal recessive disorder characterized by fever, hepatosplenomegaly, cytopenia, hyperferritinemia, hypertriglyceridemia and/or hypofibrinogenemia, decreased NK cell activity, increased CD25 level and hemophagocytosis. Here we report a comprehensive structural analysis of a collection of 76 missense perforin mutations associated with FHL2 based on a proposed pre-pore model. In our model, perforin monomers oligomerize having cyclic symmetry in consistent with previously found experimental constraints yet having flexibility in the size of the pore and the number of monomers involved. Clusters of the mutations on the model map to three distinct functional regions of the perforin. Stability change (??G) calculations show that the mutations mainly destabilize the protein structure, interestingly however, A91V change, often suggested as a polymorphism, leads to a more stable one. Structural characteristics of mutations help explain the severe functional consequences on perforin deficient patients. Our study provides a structural approach to the mutation effects on the perforin oligomerization and impaired cytotoxic function in FHL2 patients.
Biyolojik saat modellemesi
Circadian rhythms are endogenously driven periodic oscillations of physiological, biochemical and behavioral processes within approximately 24 hours periodicity in diverse species range of orgaisms. In this thesis, we developed a detailed, predictive mathematical model for mammalian circadian clock. The concentrations of proteins are represented by ordinary differential equations, and first order mass action kinetic is assumed for every biological rate. These differential equations are solved by GAMS solver.In the first part of this thesis, we try to optimize the equations by orthogonal collocation method, which is performed by GAMS, Those equations represent mRNA concentrations of oscilatting clock genes (Pers and Crys) and they are optimized to show a circadian behavior. After obtaining the results, the profiles are compared with real time data, and it is seen that the model is accordant with empirical results.In the second part of the thesis, the aim is to knock out the genes that play role in the circadian clock mechanism. Equations, which are related to the knocked out gene, are removed from the model. Then the kinetic data set, which is obtained from the optimization, is fixed, and finally, simulation is performed. This procedure is applied for all the genes in the circadian clock. After obtaining the concentration profiles, those profiles are compared with the RT-PCR results which are found from the literature. It is seen that the model is capable of simulating the knock-out procedure.In the last part, gene dosing is performed on core clock genes. Transcriptional rate that is obtained from the optimization part is multiplied by a certain number, and the rest of the system is left with the original kinetic data set. Per1, Per2, Cry1, Cry2 genes are subjected to gene dosing and it is seen that changing the transcription rates affects the circadian clock dramatically.We built a predictive, detailed circadian model which is capable of simulating the RT-PCR concentration profiles of clock mRNAs. The most important advantage of this model is that it uses real time data, which makes the simulation biologically meaningful. Also including the post-translational modifications makes the system more realistic. The most important contribution of this study is the usage of optimization in order to find the kinetic parameters.
Aurora B ve cSrc kinazlara özgü inhibitör moleküllerin bulunması
Many cancers have been associated with the deregulation of kinases that have become a prime target for cancer treatment. In this project, we aim to determine Aurora B kinase specific and cSrc kinase specific inhibitors by conducting virtual screening on ZINC database molecules. In our first project, our vision includes different binding site of drugs for the inhibition of Aurora B that have not yet been taken into account in previous reported studies. Indeed not only we aim to find the compounds that inhibit Aurora B but we also want to find drugs that are specific to Aurora B. Those molecules, which are theoretically shown to act as good inhibitors, are also verified experimentally. Promising results are obtained which display that our inhibitors cause reduction in Aurora B activity. As a second project, we identify cSrc specific inhibitors theoretically. The molecules found for cSrc are bound in the ATP pocket and extended into the allosteric site in the inactive conformation of the cSrc kinase. They are bound in conserved ATP pocket by hydrophobic interactions and resided in the allosteric site by making direct hydrogen bonds with residue GLU310. The binding mode of these inhibitors is the same as of type II kinase inhibitors. They bind to less conserved allosteric site and conserved ATP pocket simultaneously.
Grafen ve karbon nanotüp doyabilen soğurucular ile çok yansımalı kovuklu femtosaniye kip-kilitli katı-hal lazerinin enerjisinin ölçeklendirilmesi
In mode-locking applications, single-walled carbon nanotube saturable absorbers (SWCNT-SAs) and graphene saturable absorbers (graphene-SAs) have emerged as important alternatives to semiconductor saturable absorber mirrors (SESAMs) due to their favorable optical characteristics, low cost, and relatively simple fabrication scheme. Therefore, it is of great interest to explore the limits of energy scaling in lasers mode-locked with SWCNT-SAs and graphene-SAs.In this thesis work, due to their unique wavelength range for biomedical applications, a room-temperature Cr4+: forsterite laser operating near 1.3 ?m was used in the mode-locking experiments. By incorporating a q-preserving multi-pass cavity (MPC) extension to the short x-cavity, an effective optical path length of ~ 60 m was obtained and the repetition rate of the pulses was reduced to 4.51 MHz from 144 MHz. In addition, by using double chirped (DCM) and Gires-Tournois interferometer (GTI) mirrors, nonlinear phase distortions due to self phase modulation were compensated to generate solitary femtosecond pulses. Furthermore, the power efficiency of different laser resonator architectures containing the graphene-SA or SWCNT-SA was investigated.The Cr4+: forsterite laser, mode-locked with a SWCNT-SA produced 121-fs pulses with 10-nJ pulse energy and 84-kW peak power at the wavelength of 1247 nm. The mode-locked spectrum had a width of 16 nm, corresponding to a time-bandwidth product of 0.37. Hence, the pulses were nearly transform-limited with a temporal profile of sech2.For graphene-SA mode-locking experiments, graphene samples with different number of layers were fabricated and characterized. The Cr4+: forsterite laser mode-locked with a single layer graphene-SA produced 96-fs pulses with 5.3-nJ pulse energy and 55-kW peak power at 1252 nm. In this case, the mode-locked spectrum had a width of 18.2 nm and the measured time-bandwidth product came to 0.33, also indicating that nearly transform limited solitary pulses were generated.To our knowledge, both of the results report the highest peak powers obtained to date from a femtosecond solid-state bulk laser mode locked by using SWCNT-SA and graphene-SA. Limitations to energy scaling were further explored during the experiments.
Protein yapısal verisinin protein-protein etkileşim ağlarıyla geniş çapta birleştirilmesi
Protein-protein interaction networks provide a global picture of cellular function and biological processes. Structural prediction and modeling of protein-protein interactions at the network level is crucial; it helps in assigning protein function, elucidating functional mechanisms, and drug discovery. In the first part of this dissertation, we illustrate the importance of integrating protein structural information into interaction networks, particularly in identification of selective drug targets or drugs targeting multiple proteins. Next, we present a large, proteome-scale strategy that predicts protein associations based on interface structural motifs, to analyze human ubiquitination pathway. Substrate ubiquitination is mediated by the interactions between E2 enzymes and E3 ligases. Although these E2 and E3 proteins function in a concerted manner, the principles of selectivity between them are still not entirely understood. Our method allows elucidation of which E3s interact with which E2s and how they interact with each other. Interface analysis of E2-E3 complexes reveals important clues for inferring the specificity of the interactions. In the last part, the focus is directed towards studying circadian clock regulation in p53-deficient background. p53-deficient cells are prone to tumorigenesis and cancer. However, upon circadian clock disruption by Cry knockout, they show an increased sensitivity to apoptosis by genotoxic agents and hence are protected from the early onset of cancer. We aim to elucidate how apoptotic signals are activated in p53-null cells upon Cry knockout by combining experiments with a large-scale computational approach. In particular, we perform a large-scale integration of microarray expression profiles with protein-protein interaction networks. As such, we observe that the expressions of several apoptotic genes are increased upon Cry knockout in p53-null cells and a minor amount of genes would promote cell survival leading to, in overall, a shift towards cell apoptosis. In addition, we highlight the pathways that intersect with circadian clock and illustrate how these pathways response to circadian clock disruption. Our findings would assist in identifying targets in treatment of cancers associated with p53-deficiency.
Moleküler simülasyonlar ve teorik korelasyonlar kullanarak soy gazların MOF'lardaki adsorpsiyon, difüzyon ve ayırımlarının hesaplanması
Atomically detailed simulations have been widely used to assess gas storage and gas separation properties of nanoporous materials. Metal organic frameworks (MOFs) are new potential candidates for gas separation applications due to their well defined pore structures, large surface areas and porosities. In the first part of this thesis, grand canonical Monte Carlo (GCMC) and equilibrium molecular dynamics (EMD) simulations were used to compute adsorption and diffusion of noble gases, Xe, Kr, Ar and their binary mixtures in several MOFs. Ten representative MOFs having different metal sites, organic linkers, topologies and pore sizes were chosen to examine the effects of structural properties of MOFs on their noble gas separation performances. Several properties of MOFs such as adsorption selectivity, working capacity, diffusion selectivity, permeation selectivity, and gas permeability were evaluated and compared with those of traditional nanoporous materials. Results showed that several MOFs exhibit higher selectivities than traditional zeolites in adsorption-based separation of Xe/Kr and Xe/Ar mixtures. According to simulation results, MOFs are promising candidates for Xe/Kr and Xe/Ar separations due to their high Xe selectivity and permeability. In the second part, Krishna-Paschek (KP) correlations and Ideal Adsorbed Solution Theory (IAST) were applied to predict self-diffusivities and adsorption isotherms of Xe/Kr and Xe/Ar mixtures at various compositions, respectively. These predictions were then compared with the results of molecular simulations obtained in the first part. Gas permeabilities and selectivities of MOFs obtained from theoretical correlations were compared with the ones obtained from simulations and reasons for deviations were discussed. Our results suggested that theoretical correlations can make accurate predictions and can be used instead of detailed molecular simulations for initial screening of MOFs in noble gas separation applications.
Glutamik asit 358, patates adp-glikoz pirofosforilazının normal allosterik fonksiyonu ve heterotetramer oluşumu için önemlidir
ADP-glucose pyrophosphorylase (AGPase) is a key enzyme in plant starch biosynthesis. It contains large (LS) and small (SS) subunits encoded by two different genes. Experimental and computational studies indicated that interfacial amino acids in potato AGPase are important for the subunit-subunit interactions and allosterism. Among identified amino acid residues; A91, F101, F311 and E358 on LS (identified through error prone PCR) was found to be potent for influencing the allosteric and the catalytic properties potato AGPase. In this study, effect of these mutations on heterotetramer assembly and allosteric and catalytic properties of potato AGPase were investigated. All mutations were applied on to wild type (WT) potato AGPase large subunit cDNA using site directed mutagenesis PCR. Mutants LS, together with WT-LS, was transformed to E.coli glgC- containing the potato SS cDNA plasmid, that are deficient in glycogen production. All the LS mutants except LS-E358G were able complement glgC- in E.coli. LS-E358G mutant subjected to the detailed biochemical characterization to investigate its catalytic allosteric and structural properties. Compared to WT AGPase, AGPase with mutant LS-E358G was found to have a different assembly profile, having more heterotetramers and less monomers and dimers. Its regulatory properties were noticeably altered, its affinity towards its activator reduced and inhibitor increased. Interestingly, although large subunit of potato AGPase is mostly regulatory, this mutation considerably reduced the affinity of the AGPase towards its reverse and forward direction substrates ATP and ADP-glucose, showing potato tuber AGPase large subunit affects the catalytic performance of enzyme.
Silika aerojellerin büyük ölçekli üretimi için sol-jel parametrelerinin, termal ve optik özelliklerinin incelenmesi
Transparency in thermal insulation systems provides new practical opportunities for insulation industry since transparent insulation materials can replace conventional window glazing. Silica aerogels are promising candidates to be used in such insulation systems because they are transparent and have very low thermal conductivity (10-15 mW/m.K). Silica alcogels are synthesized by sol-gel chemistry, gelled in a mold and dried by supercritical extraction with CO2 to get highly porous (porosity > 90%), low density (0.1-0.4 g/cm3) aerogels. The purpose of this study is to investigate the effects of synthesis parameters such as types and compositions of solvents on properties of silica aerogel to produce large scale silica aerogels with optimum thermal conductivity and transparency values and to use these large scale silica aerogels in a transparent vacuum insulation panel. Pore diameters, surface areas, and pore size distributions of the synthesized silica aerogels were measured with N2 adsorption-desorption technique. Optical properties were determined with using UV-VIS spectrophotometer. Transient Hot-Disk plane source and steady-state Guarded Hot Plate methods were used for analyses of thermal transport properties. It was found that decreasing the molar ratios of the solvents to precursor in the sol mixture increases transparency of resulting silica aerogel. Theoretical calculations on thermal conductivity showed that the lowest values can be reached when the density of the aerogel is between 100-200 kg/m3. Based on this information, a large scale (30x30x2.0 cm3) and transparent silica aerogel panel was produced with density of 180 kg/m3. Transparency ratio and thermal conductivity of the aerogel were measured as 88% (at 600 nm) and 16 mW/m.K, respectively.
Kuvvet alanı paramatrelerinin ZIFlerin gaz ayırımı performansları üzerine etkisi
Metal organic frameworks (MOFs) are newly emerging promising candidates for gas separation and gas storage. Zeolitic imidazolate frameworks (ZIFs) are highly robust sub-family of MOFs and they have large surface areas, high porosities and well-defined pore structures. In the first part of this thesis, Grand Canonical Monte Carlo (GCMC) and Equilibrium molecular dynamics (EMD) simulations are used and a diverse collection of ZIFs are studied to evaluate their performances in adsorption- and membrane-based gas separations. These molecular simulations are performed for both single- component gases (CH4, CO2, H2 and N2) and binary gas mixtures (CO2/CH4, CO2/N2, CO2/H2 and CH4/H2) to predict the intrinsic and mixture selectivities of ZIFs. These two selectivities are compared to discuss the importance of multi-component mixture effects on making predictions about the separation performance of a material. Gas separation performances of ZIFs are compared with other nanoporous materials and results show that several ZIFs can outperform well-known zeolites and metal-organic frameworks in CO2 separations. Several other properties of ZIFs such as gas permeability, working capacity and sorbent selection parameter are computed to identify the most promising materials in adsorption- and membrane-based separation of CO2/CH4, CO2/N2, CO2/H2 and CH4/H2. In the second part, the effect of different force field parameters on the selectivity estimation is examined. In the literature, a significant number of molecular simulation studies exists for assessing single-component gas adsorption capacities of ZIFs and all these simulations are performed using different force field parameters. Molecular simulations are carried out to predict both adsorption-based and membrane-based separation performances of ZIF-68 and ZIF-69 for CH4/H2, CH4/N2, CO2/CH4, CO2/N2 and CO2/H2 mixtures using three different force fields. Results show that adsorption selectivity of ZIFs may vary significantly depending on the force field parameters whereas membrane selectivity is much less sensitive to the force field. In addition to adsorption and membrane selectivities, various separation properties of ZIFs are estimated such as working capacity, sorbent selection parameter, regenerability, permeability and compared with the properties of other well-known nanoporous adsorbents and membranes. Results suggest that ZIF-68 and ZIF-69 can outperform traditional zeolites in separation of CH4/H2 and CO2/H2 mixtures
Endüstriyel dizel hidro-işleme ünitesinin kinetik modellenmesi ve simülasyonu
In refineries, hydroprocessing is a vital technology for upgrading the quality of petroleum. For example hydrotreating is used to remove impurities like sulfur, nitrogen and metals from feedstocks and hydrocracking is used to crack the larger molecules into valuable products. Sulfur removal is a very important issue since governments mandate lower sulfur content fuels because of air pollution by SOx which is produced during combustion of petroleum products. This study focuses on kinetic modeling of an industrial diesel hydroprocessing (DHP) process which consists of three catalytic reactor beds that carry out hydrodesulfurization and hydrocracking. Steady-state non-isothermal, pseudo-homogeneous plug flow models for the catalytic hydrodesulfurization and hydrocracking reactors are separately developed. Continuous lumping approach is used to characterize the complex reaction mixture. Three adjustable hydrodesulfurization parameters and one adjustable hydrocracking parameter are fine-tuned using available industrial data. The main purpose of developing the reactor models is to be able to do simulations under different scenarios and to predict the best operating conditions for the DHP process. Simulations show that the developed model is able to accurately predict temperature profiles in each bed, sulfur content of the product and the product distribution in the hydrocracker.
Kontrollü ilaç salımı için yeni geliştirilen ph'a duyarlı hibrid hidrojellerin görünür ışık altında sentezlenmesi
In the current research on drug delivery systems hydrogels have become an important topic due to their unique properties such as high water content and sensitivity to the physiological changes in the body. In this study, a novel method was developed for the visible-light-induced synthesis of a pH responsive composite hydrogels for controlled delivery of an anticonvulsant model drug pregabalin (PGB). The pH sensitive layer of the composite hydrogel was based on methacrylic acid grafted with poly(ethylene glycol) tethers P(MAA-g-EG). In addition, the hydrogel was functionalized with hydrophobic domains, through incorporation of crosslinked styrene-butadiene-styrene (SBS) copolymer. Swelling ratios were decreased with the addition of SBS, and as a result high hydrogel crosslink densities were observed. The composites were investigated for controlled release of PGB, and the release was analyzed to describe the mode of transport through the network under neutral and low pH conditions. In vitro human fibroblast survival assay and in vivo rabbit implantation experiments demonstrated that, these hybrid hydrogels were not toxic and had desirable biocompatibility properties. This is the first report about the synthesis of a pH responsive composite hydrogels via visible light photopolymerization. This technique could be useful for incorporation of molecules with specific functionalities so that sequential molecule delivery in response to specific stimuli could be achieved. This approach can also be used for the design of multifunctional membranes for various tissue engineering applications.
HLA-B51 ve HLA-B52'nin karşılaştırmalı moleküler dinamik çalışması: HLA-B51'in Behçet Hastalığı'ndaki patojenik rolü üzerine bulgular
Beh çet's Disease (BD) is a chronic inflammatory disorder and its aetiology is unknown. Nearly every genetic study related to BD has confi rmed the association of HLA-B51 with BD since the time the association was first recognized forty years ago. Despite the recurrent affi rmation of HLA-B51 as the strongest genetic risk factor in BD, the exact mechanism of action of HLA-B51 is still unknown. Even though BD is strongly associated with HLA-B51, it is found to be not associated with HLA-B52, which diff ers from HLA-B51 by only two residues found on the peptide-binding region. In order to understand the eff ect of these variations on the dynamics of the bound and unbound forms of the two proteins, we performed comparative molecular dynamics simulations on the two MHC class I proteins in the absence and presence of sixteen diff erent peptides. Distance distribution analysis showed that peptide binding results in a shift to a more coherent conformation in HLA-B52, while there is no signifi cant conformational shift in -B51. Atomic fluctuation analysis additionally showed that peptide binding makes HLA-B52 more stable, which is the expected case, whereas it does not have such an e ffect on -B51. Based on these observations, we speculate that the instability and floppiness of the overall peptide-bound structure of mature HLA-B51 molecules may contribute to its pathogenic role in BD, by causing ER stress induced proinflammatory signaling through unfolded protein response (UPR).
1-bütil-3-metilimidazolyum katyonlu iyonik sıvıların saf halde ve metal-oksit destekler üzerindeki kısa ve uzun dönemli ısıl dayanıklılık limitlerini belirleyen yapısal faktörler
Ionic liquids (ILs) are the first choice in many applications such as synthesis, electrochemistry, and especially in catalysis because of their tunable physicochemical properties. In catalysis field, determination of thermal stability limits of metal-oxide supported ILs is crucial for proper choice of ILs at application conditions because determined stability limits of pure ILs are not applicable for these systems. Because, ILs directly interact with metal-oxides and these interactions influence thermal stability of ILs significantly. In the first part of this study, structural factors determining thermal stability of ILs with 1-n-butyl-3-methylimidazolium, [BMIM]+, cation on SiO2, TiO2, γ-Al2O3, and MgO were determined. Results show that thermal stability limits of ILs increase with decreasing inter-ionic interaction strength. Stability limits of ILs linearly increase with increasing acidity of C2 proton on imidazolium ring, controlling inter-ionic interaction strength. Moreover, anion size significantly influences stability limits. Presence of metal-oxide lowers stability limits significantly as surface acidity decreases with increasing point of zero charge (PZC) of metal-oxide. Based on these findings a model was developed as a function of PZC and ν(C2H) to estimate stability limits of [BMIM]+-based metal-oxide-supported ILs. Finally, γ-Al2O3-supported ILs' long-term thermal stabilities were determined by isothermal TGA measurements based on 1 % mass loss after 6 h treatments. Long-term stability limits were lower more than 60 °C from short-term stability limits. Furthermore, activation energy Ea required for decomposition were determined from the results of isothermal treatments. This study was the first step of the studies on catalysts with the IL-coated supported metal complexes.
IL-1 ailesinin yapısal yönlerinin moleküler dinamik simülasyonu kullanılarak araştırılması
Interleukin-1 (IL-1) is a master mediator of innate immunity and inflammation. There is a tight regulation by receptor antagonists, decoy and soluble receptors both extracellular and intracellular levels. Members of the IL-1 Receptor family include type I IL-1 receptor (IL-1RI), IL-1 receptor-like 1 (IL-1RPL1, also called as ST2) and IL-18 receptor as primary receptors, type II IL-1 (IL-1RII) receptor as a decoy receptor, IL-1 receptor accessory protein (IL-1RAcP) as a secondary receptor. One of the IL-1 family receptor ligands, IL-1β, has a major role in immune responses. It signals through binding its primary receptor IL-1RI and its secondary receptor IL- 1RAcP. IL-1 has also a naturally occurring antagonist functions via binding to IL-1RI. Therefore, targeting IL-1R is a common therapeutic strategy for autoinflammatory diseases. However, structural basis of IL-1 antagonism is still unknown. Here we used classical molecular dynamics to reveal key aspects of the signalling complex of IL-1β and interaction between its primary and secondary receptors. We showed that high D3 domain fluctuation of IL-1RI when it is bound to antagonist can have an important role in inhibiting IL-1 signalling. In addition to IL-1 complexes, we have performed classical molecular dynamics simulations of single soluble forms of IL-1 receptors. We have found that in the absence of ligand, IL-1RI, ST2 and IL-18R1 take conformations that are dramatically different from their complex conformations. There are also experimental studies which support our findings on these different conformations. One of them is from a x-ray structure in which close form of IL- 1RI is in complex with a short peptide. In addition, SAXS studies confirm that ligand-free ST2 has different conformers in solution. These different conformers cannot participate in ligand binding; therefore, this can be a new finding on inhibitory mechanism of IL-1 superfamily.
Microçubukların frekans tepkisi ölçümleri kullanılarak yoğunluk ve ağdalık değerlerinin belirlenmesi
In this study, we investigate the resonant frequency and Q-factor of ferromagnetic nickel microcantilever immersed in Ar, N2, CO2 and CO2-N2 binary mixtures at 308.15 K and pressures up to 24 MPa. Measurements were performed using an experimental setup that includes a temperature controlled high-pressure vessel which can operate within a temperature range of 273 – 423 K and a pressure range of 1 – 30 MPa. A microchip containing microcantilevers and an electromagnet for microcantilever actuation were placed inside the vessel. The procedure followed for the determination of microcantilever frequency response then involved driving of microcantilevers with AC magnetic field at varying frequencies and detecting of the corresponding laser deflections from the driven cantilevers with a quadrant photodiode (QPD). At a constant temperature, resonant frequency and Q factor of microcantilever oscillations were found to decrease with increasing pressure as a result of increasing density and viscosity of the fluid. Experimental data was analyzed using Sader's model which describes oscillatory motion of immersed cantilevers incorporating the effects of density- and viscosity-dependent hydrodynamic forces. A very good agreement between the experimentally obtained cantilever resonant frequencies and quality factors and the predictions of Sader's model was observed. The low difference in experimental and theoretical values illustrates that our experimental approach is suitable for the density and viscosity measurement of gas and supercritical fluids and fluid mixtures at a wide range of pressures. Based on these results, we carried out simultaneous measurement of density and viscosity of nitrogen from the measured frequency responses of an oscillated microcantilever immersed in N2. To this end, using argon as a reference fluid of known density and viscosity, cantilever calibration parameters were obtained from nonlinear regression of cantilever resonant frequencies and quality factors recorded in argon. Subsequently, these calibration parameters were used in the model equations to determine the density and viscosity of nitrogen at the given experimental pressure and temperature. In the studied pressure range, the root-mean-square deviations of the measured density and viscosity of nitrogen from the reference values obtained from NIST database were 2.5% and 5.2%, respectively. Finally, we studied thermophysical properties of more complex fluid systems represented by fluid mixtures. In order to investigate the density and viscosity of fluid mixtures, CO2-N2 binary mixture was chosen as a model fluid. The average relative deviation range for different compositions of CO2-N2 binary mixture was found to be 0.96 % -13.27 % for density and 2.42 %- 15 % for viscosity when N2 was used as reference fluid.
Saf ve iyonik sıvı i̇çerikli metal organik kafesli yapılarda CH4 adsorpsiyonunun deneysel ve hesaplamalı olarak i̇ncelenmesi
Natural gas is an abundant and relatively clean energy source with a potential to replace petroleum towards a low-carbon energy future. The most challenging part of utilizing natural gas for various applications is the development of a feasible method for its high density storage. Natural gas is commonly stored as compressed or liquefied natural gas which both create economical and safety issues. An alternative approach for safe and efficient storage of natural gas, adsorbed natural gas (ANG), has drawn attention recently. For the efficient implementation of ANG specifically tailored high capacity adsorbents are required. Metal organic frameworks (MOFs) have emerged as crystalline porous materials constructed from organic linkers and metal clusters. MOFs are considered as very promising adsorbents as a result of their extraordinary structural characteristics, such as high surface area, high porosity, low density as well good thermal and mechanical stability. In the first part of this thesis, grand canonical Monte Carlo (GCMC) simulations were performed to investigate CH4 (main component of natural gas) storage performance of MOFs. Structural/chemical properties of MOFs were calculated and simple multivariate linear models were constructed to predict CH4 uptake of over 1500 different MOF structures using these properties. Moreover, the structural/chemical characteristics resulting in high CH4 uptake were identified and optimum ranges for these properties were presented. In the second part, experimental characterization and high pressure adsorption measurements for CH4, CO2, N2, and H2 were performed for one of the top performing MOFs, HKUST-1 (commercially available as Basolite C300). Incorporation of ionic liquids (ILs) were examined using 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) to enhance gas storage and separation capabilities of Basolite C300. Results suggest that incorporation of ILs in MOFs results in modified adsorption capacities for different gases, with the highest affinity towards CH4. The high pressure gas storage capacities were lowered with the addition of IL however, improved gas separation performance was observed. As a result, IL-incorporated MOFs are identified as new type of adsorbents with high potential for various gas storage/separation applications.
Nanojel içeren pH'a duyarlı kompozit hidrojel sisteminin kontrollü ılaç salımı için kullanımı
In this study, both ultraviolet (UV) and visible-light have been used for the synthesis of novel hybrid pH responsive systems composed of poly(methacrylic acid-grafted-ethylene glycol), P(MAA-g-EG), and acryloyl group modified-cholesterol-bearing pullulan (CHPOA) nanogels. The system developed here has been utilized for controlled delivery of an anticonvulsant model drug pregabalin (PGB). The hydrophilic P(MAA-g-EG) network allows for pH dependent release of a loaded therapeutic agent, where CHPOA nanogel allows for the loading of a protein or hydrophobic drug into its structure. The hybrid hydrogels were synthesized under both UV and visible light, where bulk and surface initiated photopolymerization approaches were used. Bulk polymerized hydrogels were obtained through suspension of photoinitiator within the prepolymer solution, where uniform permeability properties were achieved for the synthesized pH responsive gel network. Surface initiated photo-polymerization was based on adsorption of photoinitiator onto an underlying substrate, where pH responsive hybrid gels with crosslink density gradients were obtained. Covalently attached nanogel within P(MAA-g-EG) hydrogel was characterized by Field Emission- Scanning Electron Microscope (FE-SEM). Swelling and release studies were carried out at pH 2.2 and 7.4 to mimic the physiological conditions in stomach and small intestine. Dynamic and reversible swelling experiments demonstrated higher swelling ratio profiles for visible light cured composite hydrogels. In addition, hybrid hydrogels incorporated with 5% nanogel, or synthesized with bulk photopolymerization demonstrated higher swelling. PGB release profiles at neutral pH demonstrated similarities for altered nanogel concentrations within the composite network. Biocompatibility of the hybrid network was also characterized using HeLa cell line in vitro. This approach for multifunctional membranes could be utilized for incorporation of specific molecules such as drug or protein with specific functionalities, so that sequential molecule delivery in response to specific stimuli could be achieved.
Gözenekli koordinasyon ağı dolgulu karışık yataklı membranların baca gazı ayırımı için moleküler simulasyonu
In this thesis, the challenge of selecting porous coordination networks (PCNs) as filler particles in mixed matrix membranes (MMMs) was examined using molecular simulations. PCNs are promising nanoporous materials in gas separations because of their tunable pore sizes, high porosities, good thermal and mechanical stabilities. Gas permeability and selectivity of 200 new MMMs composed of 20 different PCNs and 10 different polymers were calculated for CO2/N2 separation. We showed that selecting the appropriate PCN as filler particles in polymers results in MMMs that have high CO2/N2 selectivities and high CO2 permeabilities compared to pure polymer membranes. Several PCN/polymer MMMs were identified to exceed the upper bound established for CO2/N2 separation. Effect of framework flexibility of PCNs on the performance of MMMs was also examined. Results showed that considering flexibility of PCNs is important for predicting gas permeability of pure PCNs but has less significance for predicting gas permeability of PCN-filled MMMs whenever the PCN volume fraction is low. For rapid screening of PCN/polymer MMMs, flexibility of the fillers can be neglected as a reasonable approximation if the filler volume fraction is less than 0.3. The methods introduced in this thesis will create many opportunities for selecting PCN/polymer combinations for MMMs with useful properties in CO2 separation applications.
Endüstriyel bir dizel hidro-işleme ünitesinin modellenmesi, en iyilenmesi ve kontrolü
Diesel hydroprocessing is an important refinery process which consists of hydrodesulfurization to remove the undesired sulfur from the oil feedstock followed by hydrocracking and fractionation to obtain diesel with desired properties. Due to the new emission standards to improve the air quality, there is an increasing demand for the production of ultra low sulfur diesel fuel. The first of the thesis is addressing the development of a reliable dynamic process model which can be used for real-time optimization and control purposes to improve the process conditions of existing plants to meet the low-sulfur demand. The overall plant model consists of a hydrodesulfurization (HDS) model for the first two reactor beds followed by a hydrocracking (HC) model for the last cracking bed. The models are dynamic, non-isothermal, pseudo-homogeneous plug flow reactor models. Reaction kinetics are modeled using the method of continuous lumping which treats the reaction medium as a continuum of species whose reactivities depend on the true boiling point of the mixture. The key modeling parameters are estimated using industrial data. Steady-state and dynamic model predictions of the reactor bed temperatures, sulfur removal, and diesel production match closely the plant data. The industrial Diesel Hydroprocessing plant operates with varying feed-stocks and large throughputs. Also, changing market conditions have significant effects on the diesel product specifications. In the presence of such a dynamic environment, the DHP plant has to run in the most profitable and safe way while satisfy the product requirements and not violating specified constraints. In the second part of the thesis, a hierarchical, cascaded model predictive control structure is proposed to be used for real-time optimization of the industrial DHP plant using developed models. The performance of the control structure is checked with closed loop simulations for both set point tracking and disturbance rejection cases.
Nanoyapılı aerojellerin ilaç taşıyıcı sistemi olarak incelenmesi
Over the past few years, nanoporous aerogels have shown a great promise as drug delivery vehicles. In this study, inorganic and organic aerogels such as silica aerogel and alginate aerogel were investigated as drug delivery systems. Moreover, a novel layered material consisting of these two distinct aerogels was prepared for the first time by encapsulating a silica aerogel with an alginate aerogel layer. To investigate aerogels as drug delivery vehicles, different methods are utilized to load drugs into them such as the addition of the drug to the reaction mixture in one of the steps before the gel formation or by supercritical deposition to the aerogels. These techniques have disadvantages such as low solubility of pharmaceutical compounds in scCO2 and possible reactions of pharmaceutical compounds with reactants used to form gels. An alternative technique is to load the drug after gel formation by contacting the gel with a solution of the drug. The drug diffuses into the liquid inside the pores. When this drug-loaded gel is subjected to supercritical drying, scCO2 not only removes the solvent from the pores but also acts as an antisolvent, which causes the precipitation of the drug in the pores of the aerogel. This is similar to the gas antisolvent crystallization (GAS) process but in this case the process takes place inside the pores. In this study, this technique was used to load paracetamol into silica and alginate aerogels with densities ranging 0.13 to 0.15 g/cm3 and 0.055 to 0.062 g/cm3 respectively. The initial concentration of the paracetamol-ethanol solution ranged from 0.25 M to 0.8 M. The factors affecting the amount and distribution of the drug inside the aerogel matrix were investigated. The Attenuated Total Reflectance (ATR) results indicated that the paracetamol diffused inside of the aerogel and X-ray Diffraction (XRD) analysis demonstrated that the paracetamol was in crystalline form. It was possible to control loading by changing the concentration of the drug in the contacting solution and also by changing the pore volume of the alcogel matrix which in turn depended on the reactant concentrations. Moreover, the process enabled very high amount of loadings such as 40 wt. % for silica aerogels and 75 wt.% for alginate aerogels compared to conventional systems and also offers an advantage for aerogels as it combines two processes such as drying and loading in a single one reducing the time and the operating expenses. On the other hand, diffusion of paracetamol inside the pores was also theoretically modeled by solving partial differential equations. Experimental paracetamol uptake was shown to be in good agreement with the model predictions without any adjustable parameters. Finally, the release of paracetamol from loaded aerogel supports in PBS buffer was investigated showing the promise of these materials as drug delivery vehicles. It was shown that native aerogels could be used as carriers for fast acting medications whereas the hybrid aerogel was suitable to achieve a retarded release profile. A mathematical model was also developed to describe the release kinetics of paracetamol from alginate aerogels comprising the swelling of the aerogel matrix, the dissolution of the drug into the pore liquid followed by its diffusion from the pores into the surrounding medium. The inclusion of these physical phenomena in the mathematical model had greatly reduced the deviations from the experimental data and resulted in good model predictions.
Toll-benzeri reseptörlerin yapısal yolaklarını oluşturarak kanser ile enflamasyon arasındaki ilişkiyi anlamak
Toll-like receptor (TLR) pathway is one of the major pathways that give rise to inflammation, which is the first line of defense against pathogens. Although it is essential for host defense, inflammation also contributes to almost all phases of tumor development. TLR pathway plays a key role in inflammation-cancer crosstalk, but the exact mechanisms how they contribute to this remain elusive. Construction of structural TLR pathway provides insights into its roles in this crosstalk. The classical node-and-edge representation of pathways provides the big picture in a simple way, but it is incomplete. Structural pathways can help complete missing parts of such diagrams: they can help in understanding how an upstream signal is transduced to downstream; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists affect the signaling and change cellular outcome; and which alternative parallel pathways can be activated simultaneously. Constructing structural pathways is a challenging task. In this dissertation, I constructed structural network of TLR pathway by employing the powerful PRISM (PRotein Interactions by Structural Matching) algorithm and available mutational/biochemical data. I built the structural network of TLR pathway; its regulatory pathways; and also other pathways that have important roles in inflammation-cancer relation, such as different cytokine pathways, and CASP8, and TRAF3 centered pathways. The architectures that I obtained provide the structural basis for TLR clustering upon stimulation and assembly of key signaling complexes, such as "TIR domain signalosome". They also demonstrate that almost all downstream parallel pathways of TLRs are competitive and clarify decisions at pathway branching points. I showed that several negative regulators restrict TLR signaling by interfering with the formation of the key interactions and signalosomes. I also performed in silico mutagenesis analysis to characterize the effects of oncogenic mutations and found that some mutations that fall on the interfaces disrupt the interactions with their targets and enable constitutive activation of NF-κB, which might lead to chronic inflammation, which promotes oncogenesis. Our results help to understand the crosstalk between cancer and inflammation from a structural perspective.
Çok değişkenli PID kontrol döngülerinin performans değerlendirmesi ve kök neden analizi
Industrial processes are controlled with different types of controllers. Among those, PID controllers are very popular. These controllers manipulate the process inputs to keep the process stable, to reject disturbances and to regulate the process outputs at the desired set-points. PID loops include different digital and mechanical hardware. In general, control engineers at the plants are responsible for the maintenance and performance of these loops. Nevertheless, with the increasing number of the control loops at the plants, diagnosis of each loop becomes tedious. Control Loop Performance Monitoring (CPM) philosophy aims to solve this problem. Incorporating basic to advanced algorithms, CPM tries to deliver the most accurate assessment of control loops discovering the underlying causes for performance degradation. While doing that, CPM also does not manipulate the processes, instead it analyzes the already generated data. These analyses can be listed as performance assessment, oscillation detection, non-linearity detection, stiction detection and quantification, controller tuning assessment and root cause analysis. In this study, each component building the CPM philosophy is examined. The methods for each analysis component are selected based on industrial popularity. The methods are described and their strengths and weaknesses are discussed extensively. The analysis starts with the assessment of control loop performances in terms of both stochastic and deterministic techniques. Then, a common problem, oscillation, is explained and the possible methods to detect oscillations in control loops are discussed. After that, non-linearities which are the reasons behind the oscillations are discussed. Then, stiction problem which is the most frequent cause of non-linearities in control valves is described. Later, multivariable PID controllers are assessed to detect the root causes. Finally, the examined methods are connected in a single algorithm aiming to detect the root cause of performance degradation. The examined methods and the overall algorithm were tested in a plant of T¨ UPRAS¸ ˙ Izmit Refinery. The advantages and disadvantages of the methods examined are explained. The analysis showed that 47% of the loops have acceptable performance. The reasons of performance degradation were found out as oscillations, stiction and tuning problem. Finally, the root cause analysis shows that oscillations propagate and affect the other loops. 4 possible candidates for plant-wide disturbance are detected in the plant.
Amonyaktan COx açığa çıkartmadan hidrojen üretimi için yüksek ve stabil performanslı, çevre dostu ve maliyetsiz katalizör: Basit metodlarla modifiye edilmiş kırmızı çamur
Hydrogen, considered as one of the most promising alternative energy carriers, faces storage and transportation problems due to its very low boiling point, extremely low density in gaseous phase and very high density in liquid phase. Therefore, the utilization of ammonia as a storage medium for hydrogen can be a solution to the safe and effective storage problem of hydrogen. Because, it is carbon free, has a high hydrogen density (17.7 wt.%), and has an already existing infrastructure. Best performing catalysts for hydrogen production by ammonia decomposition are Ru-based catalysts suffering from high costs, whereas Ni- and Fe-based counterparts have significantly lower costs. Red mud is a by-product formed during the alumina production process, produced approximately two tons for each ton of aluminum produced. It is considered as a hazardous industrial waste due to its high alkalinity and toxic content, which makes it harmful to the environment. It contains compounds which are the oxides of mainly Fe, Al, Si, and Ti. These elements makes red mud attractive in utilizing it in application areas such as ceramics, construction, and catalysis. In this thesis, Turkish red mud, from Seydişehir, with an iron oxide content of more than 35%, was converted into a cost-free catalyst for hydrogen production by ammonia decomposition with record high stable performance. Firstly, as received red mud was subjected to simple treatment methods including acid digestion followed by ammonia precipitation to enhance the physical and chemical properties. While performing these modifications, treatment parameters were systematically varied and resulting samples were deeply characterized by XRD, XRF, and FTIR spectroscopy, SEM, TGA, and ICP-MS before and after modification. The parameters which were investigated were the type of acid used for digestion (HCl and H2SO4), molarity of the acid (2M-6M), digestion temperature (85 and 220 °C), and calcination temperature (300 - 500 °C). In general, in the modified samples, iron oxide amount was enhanced and surface area values were increased. After performing the catalytic activity measurements of these modified red mud samples at 500 °C, it was revealed that the sample with the highest surface area value of 232 m2/g (that was digested at 220 °C in 6M HCl, MRM-2) has an exceptionally high activation energy indicating a high temperature dependency. Thus, this modified red mud sample was further investigated for hydrogen production by ammonia decomposition at a higher temperature, at 700°C. MRM-700R@700 provided stable 97 0.5 % conversion for a space velocity of 72 000 cm3 NH3 h-1 gcat-1 at 700 °C, which is a record high value among all non-noble metal catalyst reported in the literature. It was elucidated that an activation period of 10 h under NH3 flow prior to the reaction forms the nitrided iron specie -Fe2N in MRM-700R@700, which is responsible for this high and stable performance. Detailed feasibility study was also performed on the economics of hydrogen production on such a cost-free catalyst based on these performance values. Utilization of red mud as a catalyst for hydrogen production by ammonia decomposition provides opportunities for i) the utilization of such a hazardous waste produced in vast amounts; ii) having a cost-free, highly active and stable catalyst for COx-free hydrogen production by ammonia.
Deterjan kalıntılarının cam yüzeylerde karaketerizasyonu
The problem of white spots on dishwasher-washed dishes has been receiving significant attention with increased health awareness of consumers. There is a need for characterization of such white spots on dishes. In this thesis, we focused on identifying the chemical components in these white spots by considering penta-Sodium triphosphate (STPP, Na5P3O10) and tri-Sodium citrate dihydrate (sodium citrate, Na3C6H5O7), the most widely used components in detergent formulations. Spectroscopic and diffraction measurements have been carried out to analyze the dishwasher washed glass sample surfaces both qualitatively and quantitatively. For qualitative analysis, surfaces of the dishware were analyzed by Fourier transform infrared spectroscopy in the attenuated total reflectance mode (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), and laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS). For quantitative analysis, UV-VIS-NIR absorption spectroscopy, Fourier transform infrared spectroscopy in the attenuated total reflectance mode (ATR-FTIR), Raman spectroscopy, laser ablation-inductively coupled plasma mass spectroscopy (LA-ICP-MS) were utilized to obtain quantitative calibration models for a range of STPP and sodium citrate concentrations (1 to 8% w/w) precipitated on glass surfaces. Then using these calibration curves, STPP and sodium citrate residues on the dishwasher-washed dishes were determined quantitatively by ATR-FTIR. In addition to these, a simple colorimetric analysis was also developed to detect residues of STPP and sodium citrate on dishwasher washed glass surfaces. Moreover, the hydrophilicity of these chemicals was measured by contact angle measurements and the toxicity assays were performed to elucidate the influence of STPP and sodium citrate on human kidney cells viability. Cell viability results showed a decreasing trend in the number of cells cultured with increasing concentrations and exposure time of sodium tripolyphosphate and sodium citrate in the medium. Results of this study provide opportunities for quantifying the detergent residues on dishwasher-washed dishes and assess their possible toxicity on live cells.
Aerojel kullanımı ile ılık hisli malzemelerin geliştirilmesi
The warm sensation is related to the amount of heat extracted from the human skin when it is in contact with a material. This heat extraction can be described by the time dependent heat flux which occurs from the skin to the object. The heat flux depends on the material properties such as thermal conductivity, density and heat capacity. Increasing warm sensation requires decreasing these properties. Urea formaldehyde is a thermoplastic polymer which is most commonly used to make toilet seats. Improving warm sensation of toilet seat has become a good marketing strategy. To enhance the thermal comfort of the seats electric heaters are currently in use. However it raises safety issues because of high possibility of water contact with the heater. This project aims to give the urea formaldehyde based toilet seats to warm sensation by incorporating aerogels which exhibits high resistance to heat flow. Urea formaldehyde grains were mixed with aerogels (silica and resorcinol formaldehyde aerogels) and hot pressed together to obtain an aerogel incorporated composite. Composites were manufactured by hot pressing this mixture at elevated pressures and temperatures in the industrial size hot press molds at the manufacture site of toilet seats. Thermal conductivity and density of the composites were measured. Changes in aerogels' density and pore properties were determined at different pressures with a laboratory scale cold press. Denser aerogels were synthesized to make aerogels more resistant to the composite manufacture pressure. Composites with dense aerogels (0.361-0.48 g/cm3) successfully reduced the thermal conductivity of native urea formaldehyde by up to 40% by using volume fractions up to 0.38. With reduced contact coefficient parameters, up to 45% reduction in the heat flux was obtained. Thermal conductivity of composites was also predicted with effective thermal conductivity models such as Maxwell and effective medium theory (EMT). At lower volume fractions Maxwell and Rayleigh models gave good predictions for the composite thermal conductivity. Effective thermal conductivity of composites with dense silica aerogels were best predicted with EMT.
Polimer elektrolit membranlı yakıt pilleri için elektrokatalizör olarak karbon aerojel destekli saf Pt ve Pt-Cu ikili alaşım nanoparçacıklarının süperkritik depozisyon yöntemi ile hazırlanması ve karakterizasyonu
Supercritical deposition method was used to synthesize carbon aerogel supported Pt, Pt-Cu and carbon black supported Pt-Cu nanoparticles. CAs with average pore diameters of 6, 8 and 19 nm (CA6, CA8 and CA19, respectively) were synthesized and impregnated with Pt(cod)me2 precursor using supercritical carbon dioxide followed by the thermal conversion at various temperatures between 200-1000˚C. All of the prepared CAs have high surface areas with very sharp pore size distributions. XRD and TEM results show increased Pt particle size with increasing conversion temperature with a homogenous distribution of nanoparticles on the CA supports. Cyclic voltammetry was used to determine the effect of CA pore properties on electrocatalytic activity. At a conversion temperature of 400 oC, the highest electrochemical surface area value were obtained for the CAs with higher average mesopore size (Pt/CA19). Furthermore, Pt/CA19 showed good mass activity whereas Pt/CA6 and Pt/CA8 had lower activity values towards ORR. The mass activity values for Pt/CA19 increased with increasing conversion temperature, except for the sample converted at 1000 ˚C which exhibited the lowest mass activity. The specific activity increased significantly with the conversion temperature up to 600 oC which gave a value six times that obtained at 200 oC. At 800 oC, the specific activity decreased slightly, probably due to a change in the CA structure at this elevated conversion temperature. The adsorption isotherms of Cu(tfa)2 on CA19 were measured in 35 oC and 10.7 MPa in scCO2 and fitted to Langmuir adsorption model. Both simultaneous and sequential SCD methods were applied for the preparation of preliminary Pt-Cu/CA19 samples, however, simultaneous SCD resulted low Cu loadings due to competitive adsorption of Pt(cod)me2 and Cu(tfa)2 on CA19. Sequential SCD was used to prepare Pt-Cu/CA19 samples. Decomposition of the precursors were carried out thermally under H2 flow, followed by the annealing under N2 at three different temperatures, 600 oC, 800 oC and 950 oC. The effects of deposition order, annealing temperature and metal composition on the average Pt-Cu particle size, dispersion, and particle morphology and electrocatalytic activity were investigated. Two sets of Pt-Cu/CA19 samples were prepared with different Pt:Cu mole ratios; first set was prepared with Pt:Cu mole ratio of 1:1 and the second set was prepared with Pt:Cu mole ratio of 1:3 using the single component adsorption isotherms of Pt(cod)me2 and Cu(tfa)2 in scCO2 and changing the deposition order. XRD and EDX mapping showed that all prepared samples formed disordered Pt-Cu alloy nanoparticles on CA19. The metal composition did not have a significant effect on the average particle size or dispersion of Pt-Cu nanoparticles. XRD and TEM images showed homogenous distribution of Pt-Cu nanoparticles on CA19 with narrow particle size distributions for all samples. All prepared samples have average Pt-Cu nanoparticles sizes between 1.8 nm and 4.5 nm. Furthermore, increasing annealing temperatures found to promote alloying process without excessive growth of Pt-Cu nanoparticles. Adsorption of first Cu(tfa)2 on CA19 resulted in low electrocatalytic activities for both 1:1 and 1:3 samples whereas the samples prepared by first adsorbing Pt(cod)me2 on CA19 had promising electrocatalytic activities. Samples with Pt:Cu mole ratios of 1:3 showed better catalytic activities than the ones with 1:1. Enhanced catalytic activity as compared to pure Pt/CA19 was obtained for Pt-Cu/CA19 sample (0.123 A/mgPt) annealed at 800 oC, where Pt(cod)me2 adsorbed firstly, with a Pt:Cu mole ratio of 1:3. The effect of support was also investigated by impregnating CA19 and Vulcan (carbon black) with Pt(cod)me2 and Cu(tfa)2 via in-situ sequential SCD method with Pt:Cu mole ratios of 1:3. The average particle size of Pt-Cu on CA19 was significantly lower (2.8 nm) than the average particle size on carbon black (4.9). Mole ratios obtained from XRD and XRF were quite close to each other when compared to other Pt-Cu/CA19 samples. Moreover, Pt-Cu/Vulcan sample resulted in higher electrocatalytic activity than the Pt-Cu/CA19 sample (0.09 A/mgPt and 0.04 A/mgPt).
CLOCK-BMAL1 transaktivasyonunu etkileyen yeni transkripsiyon faktorlerinin tanımlanması
Circadian clocks are self-sustained time-keeping systems that generate circadian rhythms with a period of approximately 24 hours. Circadian clocks are internal pacemakers that influence human physiology, endocrinology, xenobiotic detoxification, cell growth, and behavior. In mammals, the circadian clock mechanism involves several proteins that participate in positive and negative transcriptional feedback loops. Proteins involved in the positive feedback loop include BMAL1 and CLOCK proteins. These proteins form heterodimers and bind to E-box elements (CACGTG) in promoter of period (Per), cryptochrome (Cry) and other clock-controlled genes. PER and CRY proteins form heterodimers that interact with casein kinase I ε (CKIε) and then translocate into the nucleus where CRY acts as a negative regulator of BMAL1:CLOCK driven transcription. Genetic studies on mouse indicated that indeed there are more core clock components to regulate core clock at the molecular level. To identify components that have an effect on the BMAL1:CLOCK transactivation, high-throughput luciferase reporter assay was utilized to screen 1400 mammalian transcription factors. Initial screening showed that WW domain-containing transcription regulator protein 1 (WWTR1) is one of the top candidates that showed high repression activity for BMAL1:CLOCK driven transcription on Per1 promoter. Herein, I demonstrate that this repression activity is achieved by physical interaction of the WWTR1 with Bmal1 protein with co-immunoprecipitation and bi-molecular fluorescence complementation assay (BiFC). To see its effect on the circadian clock, Wwtr1 was downregulated by shRNA in NIH3T3 Per1: dluc and U2-OS Bmal1: dluc cell lines. There was damping in amplitude and advance in phase of oscillation of rhythm in both cell lines. Additionally, knockdown of Wwtr1 affected the transcriptional regulation of the core clock genes, especially transcription of the Bmal1 and Cry1 genes. Furthermore, WWTR1 appears to acts as co-activator on Cry1 and Bmal1 promoters. ChIP analysis also demonstrates WWTR1 occupation on Cry1 promoter. Collectively all these results suggest a potential new core clock component, WWTR1, for the regulation of circadian rhythms by repressing BMAL1:CLOCK transactivation and by regulating Bmal1 and Cry1 transcriptional level.
Bir moleküler dinamik analizi: Kolşisinin kaspaz-1 aktivasyonu üzerindeki etkisi
Caspase-1 is a member of a family of aspartate-specific cysteine proteases. Since there is a large number of studies of caspase-1 in inflammation processes, this enzyme became an important drug target in order to prevent the disorders which are associated with caspase-1. Colchicine, which is a common drug used for Familial Mediterranean Fever and gouty arthritis disorders, inhibits caspase-1 activation, but the mechanism of inhibition is not clearly known. Procaspase-1 is activated through oligomerization in inflammasome and then becomes auto-activated. Some studies show that caspase-1 is regulated by allosteric regulation through a hydrogen bonding network passing dimer-dimer interface and has two conformational states which are controlled by active-site and allosteric-site inhibitors. In this study, colchicine is bound to dimer-dimer interface of procaspase-1 enzyme. By using Molecular Dynamics simulations, the changes of distances and correlations between residue pairs before and after colchicine bound was calculated. Since the structural changes on active site were observed after colchicine binding to allosteric site -dimer-dimer interface-, the inhibitory effect of colchicine on caspase-1 enzyme may be through the allosteric regulation. This outcome may be guide for further drug discoveries.
Karbon dioksit ve metanın çeşitli aerojeller üzerine adzorpsiyonunun termodinamiği araştırma
Thermodynamics of carbon dioxide and methane adsorption on various aerogels was investigated to evaluate their potential as adsorbents for carbon dioxide capture and methane storage. Excess CO2 and CH4 adsorption isotherms on aerogels such as silica, resorcinol-formaldehyde, carbon and wheat starch were measured using a volumetric method in the temperature range of 298-328 K and pressures up to 120 bar. Total or absolute adsorption isotherms were calculated from experimentally obtained excess adsorption isotherms using the pore volume of each adsorbent. It was determined that silica aerogel had maximum absolute CO2 uptake of 14 mmol/g at 308 K and 35 bar and resorcinol-formaldehyde aerogel (RFA-17) had maximum absolute CH4 uptake of 22 mmol/g at 298 K and 100 bar. CO2 and CH4 adsorption isotherms for silica aerogel were well represented with the Langmuir model. CO2 isotherms for resorcinol-formaldehyde, carbon and wheat starch aerogel and CH4 isotherms for carbon and resorcinol-formaldehyde aerogels were fitted with the Freundlich model. It was also found that the excess CO2 uptake correlated well with the mesopore surface area of each aerogel at various pressures while micropore surface area significantly influenced CH4 uptake in aerogels. The isosteric heat of adorption for each aerogel was also determined from the variation of pressure with temperature at a constant excess uptake and was found to be dependent on the surface coverage. Among all aerogels, wheat starch aerogel had highest heats of CO2 adsorption and resorcinol-formaldehyde aerogel had highest heats of CH4 adsorption. Adsorption capacities of aerogels determined were comparable with other classes of adsorbents and presents an opportunity for further investigation of aerogels as potential materials for applications in carbon dioxide capture and methane storage.
Emulsiyon kalıplama yöntemiyle fonksiyonel malzeme tasarımı: Enerji ve biyomedikal uygulamalar
Incorporating functional materials into immiscible mediums has been a conventional challenge in materials science. Solid structures are formed via templating stable liquid emulsions to overcome this challenge. In the first part of thesis, we designed a composite membrane via Pickering Emulsion templating, which integrates a hydrophobic styrene-butediene-styrene (SBS) polymer phase and hydrophilic agar phase that incorporates ionic salts for anti-icing property on bitumen surfaces. We demonstrated significant freezing delay with composite-modified bitumen compared to base bitumen in different temperature controlled chambers with temperatures of -14 and -2 °C. In addition, we investigated morphological and salt release properties of composite modified bitumen and observed potassium formate release for 67 days. Furthermore, we investigated altered ionic salts consisting of potassium formate, sodium chloride or magnesium chloride. These results are promising and suggest the potential of this polymer composite-modified bitumen for anti-icing functionality and for industrially relevant applications. In seond part of thesis, we synthesized polyethylene glycol (PEG) nanospheres via water-in-water emulsion templating method based on phase separation of dextran and PEG prepolymer and achieved the synthesis of nano-scale PEG hydrogel particles for biomedical applications. Next, we investigated the release kinetics of a model drug, pregabalin from PEG nanospheres. In the last part, we synthesized photocrosslinked SBS network and designed SBS-PEG hybrid gels for sustained drug release purposes. We achieved extended release of anti rheumatoid arthritis drug from SBS-PEG gels up to 28 days. Cell-survival assay suggested that PEG nanospheres and SBS-PEG gels are non-toxic, and can be considered for controlled drug/molecule delivery.
Adsorbent ve membran metal organik yapıların moleküler simülasyonlar kullanılarak verimli sıralanması
In this thesis, efficient ranking methods for promising metal organic framework (MOF) adsorbents and membranes were defined using molecular simulations. First, MOF adsorbents that can efficiently separate CO2 from natural gas (CO2/CH4), power plant flue gas (CO2/N2) and petroleum refineries (CO2/H2) were investigated. Several adsorbent evaluation metrics including selectivity, working capacity, adsorption figure of merit, sorbent selection parameter, per cent regenerability were computed for 100 different MOFs and for each gas separation. Results showed that regenerability is a very important metric to screen the materials at the first step of the adsorbent search and MOFs can be then ranked based on their selectivities. In the second part of thesis, gas permeability and selectivity of 700 new mixed matrix membranes (MMMs) composed of 70 different MOFs and 10 different polymers were calculated for CO2/N2 separations. This was the largest number of MOF-based MMMs for which computational screening was done to date. Selecting the appropriate MOFs as filler particles in polymers resulted in MMMs that have higher CO2/N2 selectivities and higher CO2 permeabilities compared to pure polymer membranes. It was found that for polymers that have low CO2 permeabilities but high CO2 selectivities, the identity of the MOF used as filler is not important. The outcome of adsorbent evaluation and membrane evaluation results were then applied for nitrogen separation from methane (CH4/N2). Combined adsorption and diffusion data obtained from molecular simulations were used to predict both membrane selectivities and gas permeabilities of 102 MOFs for separation of CH4/N2 mixtures. The relations between easily computable structural properties such as pore sizes, surface areas and porosities of MOFs and performance evaluation metrics were also examined to provide structure-property relationships that can serve as a guide for experimental studies.
ZIF-8'in gaz tutma ve yakalama performansının [BMIM][PF6] katkısı ile değiştirilmesi
Natural gas which is mainly composed of CH4 is a cleaner energy source with higher H/C ratio compared to fossil fuels. Natural gas is generally stored as compressed natural gas (CNG) and liquefied natural gas (LNG) to provide high densities of CH4, however these storage techniques are expensive and unsafe. Moreover, natural gas has some impurities such as CO2 and N2 which may cause corrosion and low energy density. For an efficient gas storage and separation process, high capacity adsorbent materials have been used. Metal organic frameworks (MOFs) have drawn attention as porous adsorbent materials as a result of their remarkable structural characteristics, such as high surface area, high porosity, and low density as well good thermal and mechanical stability. To improve performances of MOFs, incorporation of ionic liquid (IL) into their structure has been suggested as a new approach. In the first part of this thesis, an imidazolium-based IL ([BMIM][PF6]) was incorporated into a MOF (ZIF-8) to investigate the effect of an IL incorporation on the gas adsorption and separation performance of a pure MOF. Gas adsorption measurements for CO2, CH4, and N2 were performed in combination with atomically-detailed simulations and density functional theory (DFT) calculations. Results suggest that ILMOF interactions strongly affect the gas affinity of materials at low pressure. Direct interactions between IL and MOF lead to at least a doubling of CO2/CH4 and CO2/N2 selectivities of ZIF-8. In the second part, five different phosphonium-based ILs ([P4444][TOS], [P4441][MeSO4], [P(14)666][TMPP], [P(14)666][Br], and [P(14)666][DCA]) were incorporated into ZIF-8 and [P(14)666][DCA] was incorporated into CuBTC. The aim was to investigate the effect of different families of ILs and MOFs on the gas uptake and selectivity and extend the knowledge on IL/MOF composites. Similar performance measurements were conducted on these phosphonium-based IL/MOF composites. Results show that while phosphonium-based ILs could improve the gas capture performances of MOFs, none of them could increase selectivity of MOFs remarkably. The results show that incorporation of IL into MOF structure is a promising way to improve the gas adsorption and separation performances of pure MOFs. With the help of the results obtained in this thesis study, it is possible to extend the number of IL/MOF composites prepared by using different kinds of ILs and MOFs, and they can be investigated for different gas separation applications.
ZIF-8'e 10158953 eklenmesi: Gaz depolama ve ayırma performansı
Gas storage and separation processes have been playing a significant role to overcome energy shortage. Both CH4 and CO2 exist in the natural gas; CH4 is considered as a clean energy source, while CO2 is an impurity which causes to corrosion in the pipelines and decreases the energy content of the natural gas. In the storage and separation processes of these gases, Metal organic frameworks (MOFs) are nominated as promising materials due to their high surface area and large porosities. Modification of MOFs to reach higher gas storage capacities and better separation performances has been recently started. In the first part of this thesis, incorporation of ionic liquids (ILs) into the pores of MOFs with different loadings (wt%) was investigated. [BMIM][BF4]/ZIF-8 samples were characterized using different techniques including X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Brunauer–Emmett–Teller (BET) Surface Area, Fourier Transform Infrared (FT-IR) and Scanning electron microscope (SEM). Gas uptakes of the samples prepared were measured using volumetric analysis and gas separation performances were found calculating ideal selectivities. For each sample, different gas storage and separation performances were obtained as a result of the distinct IL-MOF interactions. Results showed that 30 wt% IL-loaded MOF samples are promising materials for especially CO2/CH4 and CO2/N2 separation applications where the corresponding selectivities increased from 2.2 to 4 and 6.5 to 13.3 at 0.1 bar, respectively. 20 wt% loading can be used for storage purposes as CO2 uptake increased by 9% at 0.1 bar. In the second part of this thesis, we extended the IL-MOF pairs and studied several combinations. Same characterization techniques were used for different IL incorporations into ZIF-8 and the relationship between IL-MOF interactions and performances of composite materials was examined. ZIF-8 was modified with annealing process to investigate the CH4, CO2 and N2 static adsorption capacities and separation performances. IL incorporation into MOF offers opportunity for improvement in gas storage and separation applications. Results showed that these composite materials can be used in purification of natural gas and flue gas to overcome energy shortage.
Pt-Cu atom topaklarının genetik algoritma ve yoğunluk fonksiyonel teorisi ile global optimizasyonu
The atomic arrangements and structures of monometallic Pt and Cu clusters and bimetallic PtCu clusters composed of 2-40 atoms were determined using a genetic algorithm (GA) with multiple runs between 100 and 400. GA was designed associated with the Gupta potential energy with the aim to define atomic interactions within cluster regime. The algorithm was developed and implemented in MATLAB [1] environment. After a large number of GA runs on Pt, Cu and PtCu clusters, the algorithm successfully found the minimum energy structures. To improve our understanding of the structural and energetic properties of the mono- and bimetallic Pt-Cu clusters, a wide range of energetic and structural properties (i.e., excess, binding energy and second difference in energy, effective coordination number, average weighted bond length, and second order parameter) were calculated. Energetic analysis provide strong evidence that the lowest energy structures of Pt, Cu and PtCu clusters were stable and energetically favorable. The optimum structures for every size of Pt and Cu clusters were symmetric, regular and mainly based on icosahedron structures while PtCu clusters above 20 atoms were distorted. The lowest energy structures of PtCu clusters were found as mixed distorted icosahedrons with Pt segregation in core region whereas Cu atoms were located on the surface. Remarkably, 38 atoms of Pt, Cu and PtCu alloy clusters tend to be perfect truncated octahedron which was the similar face centered cubic packing as in bulk Pt and Cu. Further, global optimization of each composition of 10 atoms of PtCu clusters were carried out with DFT approach using Gaussian 09. Energetically the lowest energy composition was obtained as Pt3Cu7. Hydrogen and OH adsorption was studied to investigate how hydrogen interacts with Pt−Cu clusters for improving our understanding of the factors determining the reactivity. Hydrogen and OH adsorption energy and adsorption properties were found in the different charge states and in different adsorption sites as top, bridge and hollow of Pt10, Cu10 and Pt3Cu7 clusters. More negative adsorption energy indicates the stronger the adsorption since the adsorption energy measures the magnitude of the binding energy of the species to the cluster. Based on our calculations, the lowest energy structures for H and OH adsorbed on Pt3Cu7 cluster were reached in the neutral state. The most favorable adsorption site of hydrogen was found as the top site for Pt10 and bridge site for Cu10 cluster. For the case of bimetallic Pt3Cu7 cluster, the hollow site are more favorable for hydrogen adsorption but Pt-hollow site is more energetically favorable. This result indicates that H atoms show a preference for Pt atoms rather than Cu in Pt3Cu7 cluster.
Dizel motorlu ağır iş makinelerinin motor sonrası sistemi kalibrasyonu için ticari bir katalizör kullanılarak NOX'un amonyak ile seçici katalitik indirgenmesinin üç-siteli kinetik modeli
Selective catalytic reduction (SCR) of nitrogen oxides (NOx) with ammonia is an efficient process for NOx abatement in diesel powered heavy duty vehicles. In the first part of this study, mass transfer limitations for standard SCR reaction in a monolith reactor over a commercial copper-chabazite (Cu-CHA) washcoated catalyst were investigated using a single reaction model. Results revealed that the intrinsic kinetic parameters obtained at low temperatures cannot account for SCR activity at higher temperatures and external mass transfer limitations exist at temperatures above 350 °C. Accordingly, in the second part, a multi-site kinetic model, in combination with internal and external mass transfer effects, was developed for ammonia SCR of NOx over CuCHA. NH3 adsorption & desorption, NH3 oxidation, NO oxidation and standard SCR reactions as well as the N2O formation reactions were studied separately in the temperature range of 100 to 600 °C using a monolith reactor. NH3 adsorption and desorption profiles showed good agreement with a kinetic model based on three different sites for ammonia storage on Cu-CHA. These three sites are believed to be monocopper species located near/on 6-membered ring of the chabazite structure, copper oxide clusters or coppers which move to the large cages at high temperatures and sites on which ammonia binds loosely. Site densities and coefficients of the mass transfer coefficient correlation for square channeled cordierite honeycomb monoliths, (𝑆ℎ = 𝐴(1 +𝐵(𝑅𝑒)(𝑆𝑐)(𝑑ℎ/𝐿))𝐶), were regressed from NH3 adsorption breakthrough and temperature programmed desorption data. The activation energies and pre-exponential factors for NH3 adsorption & desorption, NH3 oxidation, NO oxidation, standard SCR, and N2O formation reactions were also regressed from experimental data. The three site kinetic model is in excellent agreement with the experimental data at a wide temperature range (100 to 600 °C). The model also predicted very well standard SCR reactor effluent composition at different flow rates, which were not considered during the parameter estimation. Findings of this study revealed that correlations in the literature for estimation of mass transfer coefficients in monolith reactors were not appropriate for these systems (NH3-SCR). Therefore, mass transfer coefficients should be regressed from experimental data at conditions of interest for accurate prediction of SCR activity.
Mikroalg chlorella vulgaris'ten biyodizel üretimi için süperkritik karbondioksit ile yağ ekstraksiyonunun teorik ve deneysel olarak incelenmesi
Finite availability of fossil fuels and negative impacts of anthropogenic greenhouse gases emissions causing global warming have stimulated development of alternative resources for transportation fuels. Among alternatives, liquid biofuels such as biodiesel is attractive as they can be directly utilized in existing infrastructure. Recently, microalgae lipids has attracted increasing attention to be used for biodiesel resources thanks to superior properties of microalgae. They can be cultivated on non-arable land without competing with human food. Their lipid productivity is much higher than agricultural crops. Lipid extraction from microalgae is one of the steps affecting economic feasibility of biodiesel production from microalgae. Supercritical CO2 (scCO2) extraction technology is considered as a promising alternative since it is environmentally friendly and prevents solvent contamination by enabling solvent free extract. In this study, scCO2 extraction of high amount of lipid producing microalgae Chlorella vulgaris lipids was investigated in the pressure range from 200 to 400 bar and temperature range from 40 to 70 °C. Microalgae cultivation was performed with 27 liter flat panel type photobioreactor. Lipid productivity was tracked by Nile red method and it was found that highest lipid productivity was reached at early stationary phase. ScCO2 extraction was compared with conventional Soxhlet extraction with n-hexane and comparable extraction yields were obtained. Moreover, it took far less time to reach same extraction yield with scCO2. Increase in pressure at constant temperature and increase in temperature at constant pressure significantly improved scCO2 extraction yield. Effluent lipid concentration curves showed a fast extraction period followed by a much slower extraction period. Sovova's model describing these periods as external mass transfer controlled and internal diffusion controlled was used to predict experimental data. Lipid solubility in scCO2 at operating conditions was predicted from slope of the first part of the extraction curve. Predicted solubilities ranged between 2.7 and 9.0 mg lipid/g CO2. Fluid and solid phase mass transfer coefficients regressed from experimental data were the order of 10-4 m/s and 10-8 m/s, respectively. Common correlations in mass transfer for forced convection were used to predict fluid phase mass transfer coefficient. Best agreement was found with mass transfer correlation Sh=2+1.1*〖Re〗^0.6*〖Sc〗^(1/3) which was developed for evaporation from drops. Fatty acid methyl esters (FAME) profiles obtained by transesterification were considerably affected by extraction method and operating conditions of scCO2 extraction. No changes on FAME profiles were detected as a function of scCO2 extraction time.
Pankreatik adacık engrafmanını iyileştirmek için biyomimetik hücre dışı ortam dizayn edilmesi
Pancreatic islet transplantation has emerged as a promising treatment for type 1 diabetes (T1D) and engraftment of beta cells after transplantation determines the success of clinical setting. However, clinical application of islet transplantation is still limited by life-long use of immunosuppressive drugs and insufficient number of islets to achieve normoglycemia. In this study, we tailored biochemical and biophysical properties of hydrogels to promote insulin secretion function and immunoregulatory potential through incorporation of mesenchymal stem cells (MSCs) and natural extracellular matrix mimetic peptides such as RGDS, IKVAV and insulinotropic peptide (GLP-1). Co-encapsulation of islets with MSCs and/or peptides contributed to significant increases in insulin secretion compared to control. Although deleterious effects of cytokines were not completely inhibited, we observed that protection against pro-inflammatory cytokines can be achieved in free and PEG hydrogel encapsulated MIN6-MSC heterospheroids. To tailor biophysical properties of islet microenvironment, we developed unique type of nano-thin coating for insulin secreting beta cell aggregates. These aggregates which were prepared as pseudoislets through hanging drop method were coated with sequential layers of nanogels using physiologically compatible medium without toxic prepolymer solutions. These coated pseudoislets were determined as viable and functional for insulin secretion. We also confirmed in vivo biocompatibility of CHPOA nanogels through subcutaneous transplantation into CD1 mouse. This study is promising and offers new opportunities through coating of insulin secreting islets with advanced functional materials under completely physiological conditions and will contribute to longer functional islets for clinical translation of cell transplantation technology and particularly for the treatment of T1D.
Dynamic modeling of erk signaling pathway: Sensitivity, bistability and oscillations
Cell signaling is the process by which extracellular information is transmitted into the cell to perform biological functions. ERK signaling pathway controls several cellular processes such as cell growth, proliferation, and gene expression. Deregulation caused by Ras mutations leads to various types of cancers. ERK signaling is triggered by binding of ligands to epidermal growth factor receptors (EGFRs). Upon binding, EGFR becomes phosphorylated on its tyrosine residues. Adaptor protein Grb2 binds to the phosphorylated EGFR and afterwards forms the Grb2-SOS complex. Ras, which is a small GTP binding protein, interacts with this complex and transforms to its active conformation by exchanging GDP for GTP. Active Ras acts as a decisive switch which starts phosphorylation of MAPK cascade that consists of Raf/MEK/ERK signaling molecules. In the literature, there exist mathematical models built for the distinct parts of this pathway. However, this thesis combines several existing models and develops a thorough model of the system starting from the ligand binding step to the nuclear processes mediated by ERK. The model is derived from mass-action kinetics and conservation laws. Several feedback loops which are embedded in ERK signaling pathway were closely studied and the range of the parameters leading to specific responses were identified. In particular, feedback loops were added based on an intensive literature review for the purpose of justifying experimental observations or in some cases for the providing new hypotheses subject to further validation. The complete model comprises 46 ordinary differential equations, 17 algebraic equations and 143 parameters. The mathematical analysis techniques, i.e. bifurcation analysis, parameter sensitivity and dynamics simulation were applied to determine the dynamic characteristics and steady-state responses of the system. We showed that any mutations or alterations in the feedback loops strength can lead to the irreversible adverse effects ultimately resulting in disease states. We establish conditions under which bistability and oscillations emerge for this important pathway. Using our model, we generated new hypotheses that hopefully can pave the way for future experimental design and verification.
Silika bazlı yüksek yüzey alanı destek malzemeli heteropoliasitler üzerinde izobüten oligomerizasyonu
Energy consumption of the world depends heavily on fossil fuels. Because the heavy crude oil is accessible at considerably lower prices than their lighter counterparts, the refineries are now motivated to process these heavy feedstocks. The units processing such feedstock produce a significant amount of light olefins as side products. A way of utilizing these low-valued side products is to convert them into more valuable liquid products. Among the alternative processes applied for this purpose, oligomerization offers a great degree of flexibility in terms of product composition. This process requires a solid acid catalyst, such as solid phosphoric acid, zeolites, cation exchange resins, and metal oxides. Because each of these catalysts has their own limitations, there is a strong need for a new type of catalyst. The requirement of a good alternative is having a high density of acid sites with tunable strength to allow controlling the product selectivity. With their unique physiochemical properties, Keggin type heteropolyacids (HPAs) offer a broad potential in this regard. Here, their potential for isobutene oligomerization is explored. For this purpose, first a screening study was performed on tungstophosphoric acid, H3PW12O40 (TPA), tungstosilicic acid, H4SiW12O40 (TSA), and molybdophosphoric acid, H3PMo12O40 (MPA), impregnated on various silica-based high surface area supports, such as MCM-41, SBA-15, and SiO2, at various loadings. The catalytic performance of more than 28 catalysts were measured under identical conditions to determine the highly performing HPA-support combination. Data indicated that the selectivity towards distillate to gasoline ratio decreased with an increase in HPA loading on TSA/SBA-15 and TPA/MCM-41 catalysts. Because the TPA has the highest thermal stability and the strongest acid strength, the TPA/MCM-41 catalysts were selected for further study to elucidate the structure-performance relationships in more detail. For this purpose, TPA was loaded on MCM-41 at fourteen different loadings ranging from 1 to 90 wt%. Detailed characterization confirmed that the TPA clusters were successfully loaded on the support. The infrared (IR) spectroscopy and X-ray diffraction (XRD) results indicated the presence of interactions between the TPA clusters and MCM-41, especially at loadings below 50 wt%, where mostly monolayer TPA dispersion was present. These interactions led to the variations in acid site density and their corresponding strength as evidenced by the results of temperature programmed desorption of ammonia measurements. Catalytic performance measurements obtained at 393 K and 15 bar indicated that these TPA/MCM-41 catalysts provide more than 75% isobutene conversion at a weight hourly space velocity (WHSV) of 46 h-1, significantly higher than what the most of the solid acid catalysts provide under comparable conditions. Results further showed that the catalysts were more selective towards distillate range products especially at very low TPA loadings. The relative selectivity of trimers over dimers in the oligomerization product pool was four at a TPA loading of 1 wt% and decreased to 1.5 with increasing loading. Ruling out the presence of any strong correlations between the acid strength and catalytic performance, the data presented a strong dependence of the product selectivity on the availability and vicinity of the acid sites. These results present a broad potential of utilizing HPAs supported on high surface area supports as an alternative family of catalysts for high performance in olefin oligomerization. Ability to adjust the TPA loading in a wide range offers opportunities for tuning the product selectivity.
İyonik sıvı/metal organik kafesli yapı kompozit malzemelerinin rasyonel tasarlanmasına yönelik: İyonik sıvılardaki iyonlar arası etkileşimin etkisi
Metal-organic frameworks (MOFs) are nanoporous materials, consist of organic linkers and inorganic metal constituents. Because of their structural functionalities, they have been investigated for a variety of applications such as gas storage and separation, catalysis, and sensing. To introduce further functionality into MOF structure and modify the framework for a target application, ionic liquids (ILs) have been used as a simple post-synthetic modification agent. Since the ILs are composed of ion pairs, by changing either the structures of cations or anions, one can synthesize an almost infinite number of varieties with different physicochemical properties. The challenging part in the modification of MOFs with IL incorporation is the proper choice of an IL. In this thesis study, the effects of interionic interaction energy in ILs on gas storage and separation performance and the thermal stability limits of the composites were investigated by introducing two different systematic changes on the IL structure: changing the anion structure and methylation of the proton on the C2 position of the imidazolium ring. In the first part, three different preparation techniques were examined to synthesize an IL/MOF composite. Influence of different preparation routes on the adsorption performance of the composite as well as its structural properties was investigated. Wet impregnation technique was selected as a proper way of preparing IL/MOF composites compared to ship-in-a-bottle and incipient wetness methods. Since this technique is not time and energy consuming, it can be employed to synthesize any combination of IL/MOF composite materials. In the second part, a family of imidazolium-based ILs with the same cation, 1-butyl-3-methylimidazolium [BMIM], and seven different anions was selected and incorporated into a well-known MOF, CuBTC (HKUST-1). Effects of interionic interactions in ILs on the extent of interactions between IL and MOF were investigated. The results showed that ILs mostly interact with the open metal sites of CuBTC, and extent of these interactions depends strongly on the IL structure. Consequences of these interactions on the thermal stability limits and adsorption performance of the IL/MOF composites were examined. Results exhibited that interionic interaction in ILs which can be probed spectroscopically with C2−H vibration frequency is the dominant factor in determining the extent of interactions between IL/MOF. In the last part of the thesis, the influence of methylation on the C2 position ofiv an imidazolium type IL ([BMIM][PF6]) was investigated. Results showed that methylation in ILs affects the interactions between IL and MOF and results in improvements in gas separation performance. Results provided in this thesis study can help to systematically design IL/MOF pairs by selecting a proper IL depending on the desired application.
Oksijen indirgeme reaksiyonu için N-katkılı Co teşvikli karbon aerojel elektrokatalizörlerinin süperkritik akışkan yardımı ile hazırlanması ve katalizördeki aktif yapıların doğasının incelenmesi
Oxygen Reduction Reaction (ORR) plays an important role in various devices that are under development for energy conversion and storage such as fuel cells and metal-air batteries. Although carbon supported Pt and its alloys are considered as the best ORR catalysts up to now, high cost and limited supply of noble metals severely hinders the widespread commercialization of these devices. Thus, development of Pt-free carbon based nanomaterials for ORR has been attracting increased attention. Among others, transition metal containing (usually Co, Fe) N-doped carbon materials are the most promising candidates. In this study, a new highly active family of non-noble Co promoted N-doped Carbon Aerogel catalysts (N-Co-CA) were developed which prepared by a supercritical CO2 assisted technique combined with NH3 treatment. The catalyst displayed similar activity as a commercial Pt/C catalyst with a superior methanol tolerance. The active sites are created during the complex transformation of an organic aerogel to a carbon aerogel in the presence of cobalt by ammonia as the source of nitrogen and pyrolysis medium. In the first part, the effect of various parameters on structural and electrocatalytic properties were investigated. The effect of pyrolysis temperature was examined in the range of 700 oC to 1000 oC, and the mass activity for the ORR had a maximum at 800 oC. The TEM images revealed the existence of Co nanoparticles covered by carbon shells in the samples pyrolyzed at 800 to 1000°C. The effect of Co content on ORR activity was also investigated by varying the Co loading between 8.4 wt% and 23.7 wt%. An optimum in Co loading associated with the ORR activity was detected although the changes in the ORR activity of the samples having different Co contents are not very pronounced. Additionally, the roles of the Co and N doping in enhancing the activities of the N-Co-CA catalysts were studied. N-doped Co-promoted carbon aerogel pyrolyzed at 800 oC under NH3 flow ( 9.06 mA/mgcat) exhibited nearly double the mass activity of N-doped carbon aerogel pyrolyzed at the same temperature (5.21 mA/mgcat) at 0.8 V vs a reversible hydrogen electrode (RHE). The former catalyst exhibited the 4e- reaction pathway with a superior methanol tolerance as compared to commercial 20 wt% Pt/C catalyst for ORR in alkaline media. Moreover, the effect of N source on ORR activity was investigated.To prepare the samples in this set, urea was added to the initial solution as N source in different ratios, and TEM images displayed the presence of donut-shape Co nanoparticles. The samples prepared with NH3 treatment displayed greater mass activities compared to the samples prepared with urea. The higher activities of the samples prepared with post NH3 treatment can be attributed to possible catalytic role of Co to form C-N active sites structures for ORR during NH3 treatment. In the second part, the nature of the active sites in N-Co-CA catalyst for the ORR was investigated by selectively adding or removing the spectator species via base/acid/H2 treatments. Based on rotating disc electrode (RDE) and X-ray photoelectron spectroscopy (XPS) measurements, a strong correlation was found between the relative distribution of graphitic-N species and the mass activity. RDE and XPS data also suggested that the formation of graphitic-N sites is promoted by the presence of Co species. The results revealed that the introduction of Co during the synthesis is crucial although it is not solely responsible for the ORR activity.
MOF adsorban ve membranlarının ayırma performansları: Yük dengeleme metodlarının etkileri
Metal organic frameworks (MOFs) have emerged as strong alternatives to traditional membrane and adsorbent materials due to their wide range of pore sizes, permanent porosities, and high surface areas. Considering the potential deficit of He, it is very important to develop efficient technologies for He recovery from the natural resources. In this thesis study, the first large-scale computational study to predict He/CH4 separation performances of various MOF membranes was conducted. Predictions of the molecular simulations were compared with the experimental data for He permeability of several MOF membranes. Motivated from the good agreement between experiments and simulations, 139 different MOF membranes were examined for He/CH4 separation. These 139 MOF membranes were compared with the traditional polymer and zeolite membranes. A significant number of MOF membranes was identified to exceed the Robeson's upper bound due to their high gas selectivities and permeabilities. Ideal and mixture selectivities of MOF membranes were also compared by performing molecular simulations both for single-component gases and binary gas mixtures. Results showed that selectivities and permeabilities calculated using the single-component gas data can significantly overestimate the ones calculated using the mixture data. Results of this study will be useful to guide the experiments for selecting the most promising MOF membranes for efficient He/CH4 separations. In the second part of this thesis, effects of using different charge equilibration methods, IQEq and QEq, on the ranking of MOF adsorbents for CO2/N2 and CO2/CH4 separations were investigated using 2244 MOF structures. Results show that, CO2 uptake is more sensitive to the charge assignment methods due to its quadrupolar nature. IQEq method was found to overestimate the adsorption selectivities and adsorption performance scores (APSs) of MOFs compared to the QEq method. The Spearman's rank correlation coefficients (SRCC), quantifying the similarity on the adsorption evaluation metrics predicted from two different sets of simulations using the IQEq and QEq methods, were found to be in the range of 0.73-0.84, indicating that there is a good similarity between the MOF rankings performed by using two different charge equilibration methods. Thus, it might be a good strategy to start a high-throughput computational screening study with the IQEq and narrow down the list of MOFs before implementing the DDEC method. Results of this work will be a guide for future computational studies to screen larger numbers of MOFs as adsorbents for the separation of quadrupolar molecules.