Phd Degree / Doktora
Permanent URI for this collectionhttps://hdl.handle.net/11147/2869
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Doctoral Thesis Investigation of the Effects of Ketogenic Diet Therapy in a Mouse Model of Gm2 Gangliosidosis(01. Izmir Institute of Technology, 2024) İnci, Orhan Kerim; Seyrantepe, VolkanGM2 gangliosidosis is an autosomal recessive lysosomal storage disorder in which GM2 ganglioside is accumulated, especially in the brain. GM2 gangliosidosis is divided into three different variants: Tay Sachs (B-variant or type I), Sandhoff (O-variant or type 2), and GM2AP deficiency (AB-variant). Accumulation of the GM2 ganglioside in brain causes disease pathology as neurodegeneration and neuroinflammation. Our lab first displayed the novel GM2 gangliosidosis type-I mouse model (Hexa-/-Neu3-/-). Compared to control, this model could survive a maximum of five-months due to severe pathologies, neurodegeneration, and neuroinflammation. The ketogenic diet is high-fat and low-carbohydrate/protein diet that triggers burning fat instead of carbohydrates. The ketogenic diet is used comprehensively in neurodegenerative disorders such as Sandhoff, Alzheimer’s, and Parkinson’s to regulate inflammation, neurodegeneration, and autophagy. In addition, elevation of CCL2 expression in Hexa-/-Neu3-/- mice resulted in increased amounts of active microglia and astrocytes. Therefore, the CCL2/CCR2 signaling inhibitor of propagermanium was used in addition to ketogenic diet. Thus, reducing neuroinflammation is aimed to be more effective as a combined therapy. In my Ph.D. thesis, expression and protein levels of autophagy and inflammation-associated genes were analyzed in the mouse brain to exhibit whether beneficial effects on autophagic flux and neuroinflammation are found after the ketogenic diet and propagermanium treatment. The pathology of the GM2 gangliosidosis mouse type-I brain was illustrated by thin-layer chromatography and immunofluorescence staining to display whether the ketogenic diet affects the ganglioside metabolism. Briefly, ketogenic diet therapy and its anti-inflammatory and neuroprotective effects were explored in the GM2 gangliosidosis mouse model.Doctoral Thesis Effects of Telomerase Activators on Monoclonal Antibody-Producing Cell Lines and Stem Cells, and Their Utilization in Industrial Productions(01. Izmir Institute of Technology, 2024) Kuru, Gülten; Bedir, ErdalAging is a physiological and multifactorial biological process of functional decline in any living organism. Telomere shortening, high levels of reactive oxygen species (ROS), and cellular senescence are the primary physiological changes that accompany aging. While there has been an increase in human life expectancy in recent decades, there has not been a concomitant increase in healthy aging. Degenerative diseases, including musculoskeletal disorders such as osteoporosis and osteoarthritis, have been found to be directly linked to aging. Age-related degenerative diseases are devastating diseases that cause millions of deaths worldwide each year and place an economic and psychological burden on society. Due to the ever-increasing number of patients, there is a huge demand for novel therapeutic approaches to treat degenerative diseases. Two main approaches are at the forefront of technology for the treatment of degenerative diseases: stem cell transplantation (regenerative medicine) and monoclonal antibody-based therapy. Indeed, it is well known that there is a strong correlation between disease pathology and telomeres. In fact, the possible therapeutic effects of telomerase activation have been evaluated in diverse backgrounds to cure and prevent various diseases. Within the scope of this thesis, we aim to investigate the effects of telomerase activator novel molecules from Astragalus sp., obtained in our previous studies by biotransformation of cycloastragenol (CG) via the plant's endophytic fungi on the health span/lifespan of mesenchymal stem cells (MSCs) during in vitro expansion and their osteogenic differentiation. Additionally, the efficacy of these compounds was investigated in the monoclonal antibody (mAb) production process in terms of mAb productivity. Based on the outcomes of the study, novel telomerase activators deriving from natural resources of our country have significant potential in stem cell research, thus regenerative medicine, since promising results were obtained for the clinical use of these novel molecules. Our data also suggest that molecules simultaneously promote osteogenic differentiation and telomerase activation.Doctoral Thesis Optimization of Zinc Oxide Based Metal - Semiconductor Junction Interface Properties and Applications for Optoelectronic Devices(01. Izmir Institute of Technology, 2024) Güzelaydın, Abdurrahman Halis; Tarhan, EnverThis thesis manifests an experimental investigation on the optoelectronic characteristics of wide band gap thin film zinc oxide semiconductor – metal junction and performance enhancement of ultraviolet photo detectors fabricated utilizing this metal-semiconductor interface. Pristine zinc oxide, aluminum doped zinc oxide and amorphous In-Ga-Zn-O thin film samples with thicknesses varying between 50-250 nm were fabricated from 2' ceramic targets via magnetron sputtering method. Surface properties and thus the zinc oxide – metal junction interface was optimized by altering sputtering parameters. Sputtering gas pressure, power and temperature was varied between 1.5 – 5 mTorr, 50 – 120 W and 25 – 500 °C, respectively. To determine the effects of energetic ion bombardment on the films' surface properties, biases ranging from 5 to 15 W were applied to the substrates during depositions. A 5 nm thick silicon dioxide passivation layer was deposited on zinc oxide thin films to suppress persistent photoconductivity effect. Furthermore, a thermal treatment under ultraviolet irradiation and was applied specifically to amorphous In-Ga-Zn-O thin films after device fabrication to improve their ultraviolet sensing capabilities. Optoelectronic spectral responses of devices were assessed experimentally by using transient photocurrent spectroscopy method. An ultraviolet light source with a 275 nm peak wavelength at 500 µW power was used as illumination source. All devices exhibited photoconductor behavior with ohmic metal-semiconductor junctions under 5 V bias. Amorphous In-Ga-Zn-O Sample 10 attained a dark current of 140 nA and reached a photocurrent level of 3.8 µA with a photo-to-dark current ratio of 27, yielding a spectral response of 1830 A/W. The calculated external quantum efficiency for this device was 825000%.Doctoral Thesis Dynamic Wear Simulations of Hip Implants for Daily Life Activities(01. Izmir Institute of Technology, 2024) Alpkaya, Alican Tuncay; Mihçin, ŞenayTotal hip replacement is widely used around the world for patients whose hip joints lost their functionality. Despite its wide applications and technological developments taking place in the recent years, it still does not produce near-perfect results. It has been observed that many patients with implants have their range of motion often restricted. Although there has been literature covering the daily life motion profiles in Western societies, , it has been observed that a through database of activities including sitting, worship, and lifestyles suitable for Middle Eastern societies is non-existent.Therefore, it is difficult to determine the lifespan of implants used especially in these societies and to determine their wear rates with accuracy. In this thesis, I have utilized the first comprehensive database of daily activities of Turkish population, which was formed using the state-of-the-art motion capture (MOCAP) technologies at Biomechanics and Motion Capture Laboratory of IZTECH. The range of motion and reaction force data were calculated using the inverse kinematics and kinetics methods previously. This previously calculated boundary conditions are fed into the finite element models of hip implants to simulate ten distinct daily life activities Asian style sitting, normal walking cycle, obstacle crossing, Stoop lifting, Squat lifting, Ruku' and I'tıdal, Ruku to Sujud, Sujud, Ascending stairs, and Descending Stairs. The dynamic simulations of hip implants under these boundary conditions are performed in this thesis. In this thesis, a computational wear methodology is utilized to assess the wear performance of hip bearing surfaces under these boundary conditions. Each comprehensive computational wear simulations of each of these daily life activities over five million cycles is performed to provide omputational evidence on the wear rates to assess the wear performance of the bearing couple. The wear prediction model could be utilized to provide guidance on the design parameters with the aim of prolonging the life span of hip implants.Doctoral Thesis Experimental and Numerical Investigation of the Impact Resistance and Impact Damage Tolerance of a Carbon Fiber Reinforced Thermoplastic Polyphenylene Sulfide (pps) Matrix Composite(01. Izmir Institute of Technology, 2024) Seven, Semih Berk; Güden, Mustafa; Taşdemirci, AlperThe impact resistance and impact damage tolerance of an aerospace grade high performance 5 Harness Satin woven fabric carbon fiber reinforced/polyphenylene sulfide matrix (CF/PPS) thermoplastic composite were investigated experimentally and numerically. The numerical modeling was performed using the experimentally determined parameters of material model MAT-58 and Hashin failure criteria in LS-DYNA using the single shell and stacked shell models. The numerical models of the low velocity impact (LVI) tests showed good correlations with the experimental tests while the stacked shell model showed nearer results with the experimental tests. The stacked shell model also estimated the LVI test delamination areas, which were comparable with the experimental damage areas. The LVI tested coupons were further subjected to the compression after impact (CAI) tests in order to determine the damage tolerance of CF/PPS composite. The CAI tests were modeled using the single shell model. The numerical models of the CAI tests showed very similar trends with the experimental CAI tests. The trends were shown to be more converging in the specimens tested at 3 m/s and above in the LVI tests. Lastly, three high velocity impact (HVI) tests were performed at around 100 m/s. The failure mode of the HVI tests was shown to be very different from that of the LVI tests. The long longitudinal and transverse cracks were formed in the HVI tests. The delamination damage in the HVI tests determined using the stacked shell model was found to be more comparable with the experimental delamination damage determined by the C-Scan.Doctoral Thesis Synthesis and Characterization of Near-Infrared (nir) Emissive Conjugated Polymer Dots for Tumoroid Imaging(01. Izmir Institute of Technology, 2024) Karabacak, Soner; Yıldız, Ümit HakanThis thesis describes the synthesis and characterization of near-infrared (NIR) emissive conjugated polymers and their polymer dots (Pdots). The Pdots were exploited to image the tumor cells and tumor spheroids. The penetration behavior of NIR emissive Pdots was characterized in five different tumor spheroid models. Three different polymerization techniques were tried to synthesize the NIR emissive polymers, namely oxidative, direct arylation, and Stille polymerization. The obtained NIR emissive polymers underwent structural and optical characterization. P1 was chosen as a model polymer to obtain Pdots from NIR emissive polymers for imaging tumoroids. Pdot preparation includes using ultrasonic emulsification to modify nonionic D-A-D type alkoxy thiophene-benzobisthiadiazole-based conjugated polymers (P1) with amphiphilic cetyltrimethylammonium bromide (CTAB). The technique yields Pdots with a significant positive surface charge of +56.5 mV ± 9.5 and an average hydrodynamic radius of 12 nm. Optical characterization reveals that these Pdots were found as emissive in the NIR region, with a maximum wavelength of 860 nm. These Pdots possess colloidal and optical properties that make them appropriate for use as fluorescence emissive probes in bioimaging applications. The advantageous use of positively charged Pdots has been proven in diffusion-limited settings such as tissues, specifically in certain tumor spheroid models produced from the tumoroid cell lines. After the fluorescence imaging analysis, the Pdots' emission intensity profile indicates that they have high penetration capability into the tumoroid models' center parts. The results show that Pdots with a single-chain donor-acceptor polymer structure that has been cationized with CTAB can penetrate through dense materials over about 1 μm. This provides valuable insights into the progression of targeted theranostic strategies in cancer therapy.Doctoral Thesis Evaluation of Thermal Comfort Conditions During Training in Physical Fitness Spaces(01. Izmir Institute of Technology, 2024) Avcı, Ali Berkay; Başaran, TahsinPresently, fitness centers have become extensively occupied spaces. These higher-activity-level spaces require different thermal comfort parameters than other indoor environments. Therefore, it is crucial to provide the comfort that users need during their physical exercise. Human body during exercise requires different thermal comfort conditions and higher fresh air supply rates than sedentary activities. The standards for fitness centers do not provide specialized thermal and spatial instructions for the fitness spaces. This thesis focuses on investigating the thermal and spatial conditions of exercise spaces. To determine ideal exercise space conditions, a thermal and flow analysis involving experiments and 3D simulations in a computer environment were employed. The study specifically examined spatial factors such as ceiling height, lateral and frontal distances between machines, and vent locations, along with thermal factors like inlet temperature and air velocity. A thirty-minute constant work rate exercise test at moderate intensity was conducted in a controlled climatic chamber with six participants. The experiment's conditions were replicated and verified in CFD software using the collected data. Then, computational models for various environmental and spatial scenarios for a five-person cycling class were generated. Employing the L9 orthogonal arrays method, nine spatial scenarios with three thermal operations were simulated. Optimal factor levels were determined based on thermal comfort conditions by predicted mean vote (PMV) around the thermal plumes. The findings indicated that a ceiling height of 5m, lateral and frontal distances of 1m and 0.5m between machines, and ventilation strategy with ceiling located inlets at a condition of 18°C and 0.2m•s-1 performed optimal results.Doctoral Thesis Local Citation Recommendation With Graph Convolutional Networks(01. Izmir Institute of Technology, 2024) Keklik, Onur; Tuğlular, TuğkanLocal Citation Recommendation is a task that finds the missing reference in the corresponding citation placeholder. It is mainly contextual since context identifies the citation. On the other hand, a context can be a descriptor for a set of papers. In other words, there can be more than one candidate citation for a context. Thus, a further matching of a context with candidate papers is beneficial. Titles and abstracts of candidate papers serve as a global context to match with the local one. This work proposes a state-of-the-art approach for the Local Citation Recommendation task that exploits the similarities between global and local contexts to generate citation predictions. By utilizing a Graph Convolutional Network (GCN) with BERT embeddings, our proposed model demonstrates superior performance over previous methods. It not only outperforms all prior approaches on the benchmark datasets of ACL-200, FullTextPeerRead, RefSeer, and arXiv but also strikes a balance between speed, memory, and computational requirements. Once deployed as a production-level Local Citation Recommendation, it is fast enough to enable real-time recommendations for researchers.Doctoral Thesis Reliability Assessment Based on Structural Health Monitoring Data and Bayesian Updating of Structural Models(01. Izmir Institute of Technology, 2024) Uzun, Ertuğrul Türker; Aktaş, Engin; Hızal, ÇağlayanFinite element (FE) models are commonly used in numerical modeling of structures, but their assumptions can lead to inaccuracies and uncertainties. To address this, FE model update methods have been developed, calibrating the model based on structural health monitoring (SHM) data. However, a general framework for realistic life cycle performance assessment of structures using monitored data has not yet been presented. Bayesian modeling can characterize uncertain structural parameters as random variables, but it is complex and time-consuming. Metamodeling techniques, which are effective stochastic predictors, can be used to decrease the computational burden of model updating. Adapting a Polynomial-Chaos-Kriging (PCK) metamodeling technique to Bayesian model updating in order to reduce uncertainty and circumvent computational challenges using SHM data in order to assess the reliability of structures more precisely is the objective of this research. Therefore, the effectiveness of the proposed method has been tried and demonstrated through experimental and numerical studies. An experimental study of a bridge column is used to evaluate the reliability of structures subjected to various corrosion effects. As a result, the proposed solution method reduces computational costs and enables an updated FE model to be closer to real structure measurements. The updated models are found to be more reliable in reliability evaluations, providing more accurate predictions on issues like structure safety, service life, and maintenance cost compared to non-updated models.Doctoral Thesis Designing Composite-Based Cylindrical Structures and Manufacturing Composite Prototypes by Filament Winding Method(01. Izmir Institute of Technology, 2024) Martin, Seçkin; Tanoğlu, MetinThis study reports the design, finite element modeling, optimization, fabrication and testing of relatively thick (radius/thickness ~ 7) and long carbon fiber reinforced polymers produced by filament winding against buckling damage under axial loading. The optimum winding angle and stacking sequence against Linear (Eigenvalue) buckling were determined in accordance with the predetermined design requirements utilizing genetic algorithm (GA) optimization via MATLAB. During the optimization process, the critical buckling load factor (λcr) was assigned as objective function, design constraints were natural frequency (fn) and angle of twist (Φ), and ply angles were considered to be variable and restricted with 20 to 87-degree continuous fiber angles in the laminate sequences. As a consequence of the test results, λcr of the proposed optimum model was found to be 3.2 times better than the reference model and both the analytical and finite element model satisfactorily predicted the critical buckling load for all CFRP rods consistent with the test results. The critical buckling loads calculated by applying a KDF of 0.95 for the finite element model and a KDF of 0.9 for the analytical solution were found to be reasonably appropriate for use in the preliminary design input. Additionally, results showed that a higher axial to the circumferential ratio of axial and bending stiffness (A11/A22, D11/D22) promises better buckling performance than other possible candidates. Finally, the microstructures of the produced rods were examined and the fiber volume ratios were calculated by means of chemical characterization.