Phd Degree / Doktora
Permanent URI for this collectionhttps://hdl.handle.net/11147/2869
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Doctoral Thesis Pre-Clinical Trial Treatment of Hepatocellular Carcinoma on Cirrhosis in a Rat Model(İzmir Institute of Technology, 2017) Zeybek Kuyucu, Ayça; Şanlı Mohamed, GülşahHepatocellular carcinoma (HCC) is the second most common cause of cancer related mortality worldwide. AKT pathway has been found activated in 50% of HCC cases, making it promising target. Therefore we assess efficacy of the allosteric AKT inhibitor or the combination of Sorafenib with AKT inhibitor compared to untreated control and to standard treatment, Sorafenib, in vitro and in vivo. AKT inhibitor blocked phosphorylation of AKT in vitro and strongly inhibited cell growth and migration with significantly higher potency than Sorafenib. Similarly, apoptotic cell was strongly increased by AKT inhibitor in vitro. To mimic human advanced HCC, we used diethylnitrosamine-induced cirrhotic rat model with fully developed HCC. MRI analyses showed that AKT inhibitor significantly reduced overall tumor size. Furthermore, number of tumors was decreased by AKT inhibitor, which was associated with increased apoptosis and decreased proliferation. Tumor contrast enhancement was significantly decreased in the AKT inhibitor group. Moreover, on tumor tissue sections, we observed a vascular normalization and a significant decrease in fibrosis in surrounding liver of animals treated with AKT inhibitor. Finally, pAKT/AKT levels in AKT inhibitor treated tumors were reduced, followed by down regulation of actors of AKT downstream signaling pathway: pmTOR, pPRAS40, pPLCγ1 and pS6K1. In conclusion, we demonstrated that AKT inhibitor blocks AKT phosphorylation in vitro and in vivo. In HCC-rat model, AKT inhibitor was well tolerated, showed anti-fibrotic effect and had stronger antitumor effect than Sorafenib. Our results confirm the importance of targeting AKT in HCC.Doctoral Thesis Non-Visual Aspects of Spatial Knowledge: Wayfinding Behavior of Visually Impaired People in Complex Urban Environments(İzmir Institute of Technology, 2016) Kan Kılıç, Didem; Doğan, FehmiEverybody perceive space multi-dimensionally however blind people are more conscientious of the non-visual constituents of space. Although there is an extensive amount of research on mobility, perception, and way-finding of blind people, there has been fewer work to show which specific aspects of built environment they focus on and they use as cues in the way they relate to their urban environment. Therefore, this study focuses on the senses of blind individuals during their way-finding process in urban contexts. Two case studies in İzmir, Turkey and Lisbon, Portugal were conducted in large-scale urban contexts. The case study in İzmir highlights the holistic and multi-dimensional perception of space by asking 9 congenitally blind participants to mark those places that they find particularly important in Kemeralti and İzmir Fair Park by verbally describing the features in the environment they attend to. It was found that auditory information was the most used environmental cues and a feeling of enclosure is the most important environmental feature during way-finding. The second case study in Lisbon was conducted with 5 congenitally blind participants to understand the strategies of congenitally blind participants with a focus on whether sounds from the environment are of primary importance for blind individuals. The most important finding is that increased familiarity with the environment, the better way-finding strategies blind individuals have. This study highlights multi-dimensional sensory experience of urban environments and non-visual aspects of spatial perception.Doctoral Thesis Exploring House Price Dynamics: an Agent-Based Simulation With Behavioral Heterogeneity(İzmir Institute of Technology, 2016) Özbakan, Ahmet Tolga; Kale, SerdarIn contemporary capitalist economies, housing is not only a shelter that satisfies a basic human need. It is also a commodity produced for exchange in markets and an asset for storing and enhancing wealth. As such, its mispricing can have repercussions for individuals, firms, industries, nationwide economies, and for the global economy. The purpose of this dissertation is to explore the price dynamics of this complex entity in an analytically tractable framework. In agreement with a recent but growing body of literature, the study shares the view that incorporating insights from behavioral economics can be valuable in such an undertaking. To support this statement, the dissertation first presents a theoretical framework that situates differing views on house prices in a wider split between neoclassical and behavioral economists. Then, the study proposes an agent-based simulation by extending a prominent real estate market model known as the Four Quadrant Model. Specifically, the extended model seeks to explore the extent to which behavioral heterogeneity and dynamic market behavior enhance the existing explanations of house price dynamics. The dissertation validates the proposed model by running a set of experiments with empirical data obtained from Istanbul’s housing market between January 2010 and September 2015. The results suggest that both the inclusion of behavioral heterogeneity and dynamic behavior are relevant in the exploration of house price dynamics. Based on the theoretical framework and the simulation results, the dissertation calls for action on the part of policy makers, researchers, and members of civic and professional organizations.Doctoral Thesis Experimental and Numerical Analysis of Flow and Heat Transfer in Double Skin Facade Cavities(İzmir Institute of Technology, 2016) İnan, Tuğba; Başaran, TahsinIn this study, airflow and heat transfer in a double skin facade (DSF) cavity were examined numerically and experimentally under natural and forced flow conditions. An experimental setup was constructed i the laboratory environment. Experiments were performed for two different DSF's airflow modes; buffer zone and external air channel. These experiments vere conducted with and without a solarsimulator integratrd t the system. Furthermore, the effect of pressure drop elements in the cavity of DSF were analyzed experimentally. After the numerical results (CFD and nodal network) were verified with experimental measurements, dimensionless heat transfer correlations were developed for the natural and forced convections. As a result, an extensive experimental data set was obtained for different working conditions of DSF. So, the dimensionless pressure loss coefficients were calculated experimentally based on the geometric configuration of the pressure drop elements in the cavity. In natural convection, with Rayleigh numbers ranging from 8.59*109 to 1.41*1010 and the increasing tendency of the average Nusselt numbers from 142.6 to 168.8 were shown. A correlation for a cavity characteristic length of 0.116 was constructed to evaluate the heat flux. In forced convection, another dimensionless correlations weredeveloped to predict the heat transfer by using. Nusselt numbers with in the Reynolds numbers ranging from 28000 to 56000 for a DSF with an external airflow mode. These correlations could be used for different characteristic length ranged betwen 0.1 and 0.16. These correlations were used for the energy performence of DSF applications for different directions and climatic zones in Turkey and compared with the single skin facede.Doctoral Thesis Development of Novel Chitosan Nanocomposites as a Controlled Drug Release System for Helicobacter Pylori Treatment(İzmir Institute of Technology, 2016) Güneş, Suna Seda; Tıhmınlıoğlu, Funda; Yılmaz, ÖzlemHelicobacter pylori is one of the most common bacterial infection and responsible for gastroduodenal diseases in humans. Due to increasing failure rate of currently used antibiotic therapies, newer drugs and therapeutic approaches are needed. Therefore the use of encapsulated cinnamon bark oil is a promising approach for H. pylori eradication. The main objective of this dissertation was to develop a novel drug delivery system using chitosan and nanoclay containing cinnamon bark oil to be released in a controlled manner in gastrointestinal system for H. pylori eradication as an alternative or complementary to conventional antibiotic treatment. Minimum inhibition concentration (MIC) value of cinnamon bark oil was determined. Cinnamon bark oil loaded chitosan nanocomposite microspheres were produced by spray drying. The prepared microspheres were characterized for particle size & morphology, encapsulation efficiency, surface charge, mucoadhesion, degradation, swelling and drug release. Antimicrobial activity of the microspheres against H. pylori were investigated. In vitro cell viability of fibroblast and gastric epithelial cells were evaluated. In vitro cellular uptake and binding studies of microspheres were investigated by using gastric epithelial cells. MIC value of cinnamon bark oil was found as 8 μg/mL. Nanoclay incorporation decreased the biodegradation of nanocomposite microspheres and improved the release of cinnamon bark oil. Drug release mechanism was anomalous diffusion which refers to combination of diffusion and erosion controlled. The prepared microspheres showed strong mucoadhesive property. Oil released from prepared microspheres inhibited H. pylori growth. Although cinnamon oil showed cytotoxic effect above 31 μg/mL, the oil encapsulated chitosan microspheres did not show any cytotoxic effect on NIH3T3 and MKN45 cells. The prepared microspheres were able to get internalized into MKN45 cells and had great incorporation activity. The results of this study demonstrated that cinnamon bark oil loaded chitosan nanocomposites may serve as biocompatible and effective gastroretentive drug carrier for the treatment of H. pylori infection.Doctoral Thesis Natural and Synthetic Silica Incorporated Chitosan Composite Scaffolds for Bone Tissue Engineering Applications(İzmir Institute of Technology, 2016) Tamburacı, Sedef; Tıhmınlıoğlu, Funda; Tıhmınlıoğlu, Funda; Havıtçıoğlu, HasanRecently bone tissue engineering studies have focused on the development of 3D scaffolds that can organize the tissue regeneration in natural way with appropriate porosity and reinforced the structure. Natural polymer-based composites have been focused with more attention than synthetic polymer composites for bone tissue engineering applications because of their biocompatibility and biodegradability. In this work, the goal was to combine the useful biomaterial properties of both chitosan and silica to design biocomposite organic/inorganic biomaterials for bone tissue engineering applications. The composite scaffolds were fabricated by freeze drying method bu using two different silicas; natural silica; Diatomite and synthetic silica, octa (tetramethylammonium) polyhedral oligomeric silsesquioxanes (OctaTMA-POSS). The effects of silica type and loading on the mechanical, morphological, chemical, surface properties, wettability and biocompatibility of composite scaffolds were investigated and characterized by using SEM, AFM, contact angle analysis, swelling study, protein adsorption assay, biodegradation and biomineralization tests. WST-1 cytotoxicity, cell proliferation with rezasurin and alkaline phosphatase activity assays were performed to determine biological activity of the composite scaffolds. In vitro biomineralization on scaffolds was determined by Von Kossa and Alizarin red staining. POSS and diatomite incorporation increased the surface roughness. Chitosansilica composites exhibited 82-90% porosity. Wet chitosan-silica composite scaffolds exhibited higher compression moduli compared to pure chitosan scaffold in 67.3- 81.4kPa and 78.1 to 107.6kPa range respectively. Average pore size range of chitosandiatomite and chitosan-POSS composite scaffolds was obtained as 15-180μm and 220- 300μm, respectively. Results indicated that chitosan-silica composites did not show any cytotoxic effect on 3T3, MG-63 and Saos-2 cell lines. Chitosan-silica composites were found to be favorable for osteoblast proliferation. Diatomite and POSS incorporation showed promising effects with enhancing ALP activity on hFob cells. Therefore, these composite scaffolds could be used for bone tissue engineering applications.Doctoral Thesis Differences in the Uses and Needs of Neighborhood Parks: a Case Study About Female Park Users in Balçova (izmir, Turkey)(İzmir Institute of Technology, 2016) Kaştaş Uzun, İpek; Şenol, Fatma; Şenol, FatmaNeighborhood parks as important public open green spaces are supposed to provide certain opportunities of improving physical and mental health, socializing with others and developing public expression and identity in neighborhoods. However, on the contrary to ideal definitions of public open green spaces as open and accessible to all groups of the society, in real life this “access” is not guaranteed for all, mainly due to unequal distribution of resources. Especially certain groups of the society experience urban inequalities due to unequal distribution of resources. Women is one those groups who experience urban inequalities. The aim of this thesis is to produce a comprehensive research method that adopts a need-based approach to understand underlying causes of different user groups’ park needs and uses by looking at the different experiences of women in neighborhood parks based on their park perceptions as an example. Therefore, I conducted a case study in the neighborhood parks in Balçova, İzmir, Turkey with "mixed method" as a combination of both qualitative and quantitative data collection and analysis methods. I realized detailed observations, questionnaires, structured and un-structured interviews with Balçova residents in neighborhood parks and community houses. As a result, this study contributes to the scientific literature with the produced comprehensive research method, park improvement suggestions that consider the differences in the needs and uses of neighborhood parks and a raised awareness regarding the park needs of women, especially the ones who are bound to neighborhood space with limited social and leisure activity opportunities.Doctoral Thesis Development of a Database for the Restitution Phases of Kurşunlu Khan in Manisa(İzmir Institute of Technology, 2016) Saygı, Gamze; Turan, MineHistoric buildings are not constant assets, they are representations of mankind and cultural systems throughout the time. In such a context, it is important to enlighten the process of building’s evolution by means of restitution(s), i.e., descriptions of different (re)compositions of buildings for different historical states. Hence, restitutions are used as works of synthesis in architectural conservation, and it is a mandatory part for it. On the other hand, representation of information beyond geometric, spatial and physical characteristics of a historic building carries a crucial importance for a holistic understanding of changes in those restitutions. This requirement is a multi-fold manner consisting of representation, archival, assessment and management aspects. Regarding those aspects, databases offer promising possibilities. Nevertheless, covering the requirement of the restitution state(s) is yet quite challenging if also visualization in digital three dimensional (3D) platform is considered, which is the most desirable way since it offers users an unrestricted and holistic visualization. Accordingly, this thesis proposes a methodology for the development of a database for the restitution states of a historical monument covering not only geometric and spatial aspects, but also historical resources. The thesis has a motivation to make sharing of restitution information, and decreasing future investigation effort in order to reach information of different historic periods. In this frame, Kurşunlu Khan in Manisa, Turkey, a typical building type of Ottoman architecture (şehiriçi hanı), dating back to 15th century, is selected for testing the methodology. The principles for collection and analysis of the data regarding the case study, structuring the database, and its visualization and access possibilities are defined. The thesis concludes that database may be an efficient tool supporting both the planning of a restoration project, and archiving of comprehensive results for later interventions and research. The resulting visualization options through the database and semantically enriched 3D model effort to make an easier understanding of historic changes specific to the monument. The database is open for improvement with conservation-aimed information.Doctoral Thesis Development of Solid Phase Microextraction (spme) Fibers for Various Analytical Applications: (i) Selenium Speciation in Waters. (ii) Separation and Determination of Triclosan and Triclocarban in Waters(İzmir Institute of Technology, 2016) Ziyanak, Esen; Eroğlu, Ahmet EminIn the first part of this study, four selenium species namely selenite, selenate, selenomethionine and selenocystine in water samples were tried to be separated using single solid phase microextraction (SPME) fiber on the same chromatographic run. Bare silica fibers were immersed into agarose matrix containing nano zerovalent iron (nZVI), ceria (CeO2) or zirconia (ZrO2). After characterization of fibers sorption/desorption parameters were optimized and standard reference materials were used to validate the proposed method. Direct mode of SPME method was used to extract the analytes prior to their separation with HPLC and detection with ICPMS. The optimum conditions for the extraction of selenium species with nZVI-agarose fibers are obtained as extraction pH: 4.0, agitation speed: 700 rpm, extraction time: 60 min, desorption matrix: 10.0 mM citrate solution, desorption time: 30 min, solution temperature: 25 °C, ionic strength: no NaCl addition. In the second part of this study, same fibers were used to separate triclosan (TCS) and triclocarban (TCC) using HPLC-DAD. Among all fibers prepared, nZVI-agarose modified fibers demonstrated the best extraction performance. The optimum conditions for the extraction of TCS and TCC with nZVI-agarose fibers are obtained as extraction pH: 5.0 and 7.0, agitation speed: 400 rpm, extraction time 60 min, desorption matrix: % 90 methanol - %10 water (adjusted to pH 3.0 with acetic acid), desorption time: 30 min, ionic strength: no NaCl addition.Doctoral Thesis Categorization of Manual Lighting Control Behavior Patterns Based on Interior Layout in Offices(İzmir Institute of Technology, 2016) Cılasun Kunduracı, Arzu; Kazanasmaz, Zehra TuğçeTo reduce energy consumption due to lighting, variety of methods such as energy efficient products, daylight and lighting control systems, simulation softwares are being used. However, these methods may fall short of their potential if the end user, occupants, are not taken into consideration. Energy consumption due to lighting can be reduced further by understanding building occupants’ needs and behaviors. In this study, to understand user behavior for lighting, manual lighting control of occupants were examined. This examination compromises physical, temporal and architectural factors which affect manual lighting control behavior. Especially the focus was on interior layout to observe the relation between the architectural parameters and manual lighting control behavior. The goal of the research and experiments of this dissertation was to obtain realistic manual lighting control data in offices. First of all, various parameters including physical, visual, occupancy and architectural were observed and statistically analyzed by the conducted questionnaire, to find the most triggering/inhibiting factors for manual lighting control. Secondly three private offices were equipped to monitor the change in manual lighting control behavior with regards to occupancy, daylight penetration and interior layout. Results used to generate from the fuzzy model which offers more detailed classifications on manual lighting control probabilities. Gathered results showed that interior layout has a significant contribution to manual lighting control. As a result, if architects/lighting designers/researchers utilize the provided classifications of the tested parameters on the future studies, they can reduce energy consumption while increasing user satisfaction.