Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Studies Toward the Synthesis of Novel Mdm2 Inhibitor Candidates(Izmir Institute of Technology, 2018) Dilek, Fikrican; Çağır, AliProtein protein interactions are valuable targets to discover novel anticancer agents. One of these is the p53-MDM2 interaction. In one of these interaction MDM2 protein inhibits p53 protein and may cause cancer. New drugs that inhibit this interaction are important for the treatment of cancer. One class of these anticancer agents are morpholinone derivative. In this study, it is aimed to synthesize new morpholinone derivatives. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material for the synthesis. The first step was a trityl protection of amine with trityl chloride. Trityl protected amino acid was first reduced to N-Trt amino alcohol with LiAlH4 then oxidized to aldehyde by using Dess-Martin periodinane. The resulting aldehyde was reacted with 3-chlorophenylmagnesium bromide. This part of the synthesis was performed successfully. Then addition of methyl fumarate to this Grignard product was studied by a coupling reagents such as HATU. All attempts were failed. Then trityl group was removed by TFA and successfully coupled with methyl fumarate by using HATU. All cyclization reactions in the presence of a base like hydroxide, alkoxide or NaH to form morpholinone skeleton was failed. The cyclization reaction with the potassim carbonate in alcohol was successful and the morpholinone skeleton was formed.Master Thesis Investigation of Cytotoxic Properties of New Isoindol Derivatives in Lung and Cervical Cancers(Izmir Institute of Technology, 2019) Almusawi, Yasir; Şanlı Mohamed, GülşahCancer is one of the most common diseases in the world. Recently, there are many methods developed by researchers to treat this disease. One of these treatments is targeted for chemotherapy. It is preferred by researchers because it is less toxic and has fewer side effects than other cancer treatments. This study emphasizes the anticancer properties of the newly synthesized Isoindole derivatives. Thus, it was hoped to be a significant improvement based on new generation anticancer compounds with high efficacy and fewer side effects. The main objective of this study was to investigate the biological activity of seven newly synthesized Isoindole derivatives. The anticancer activity of these compounds was evaluated against HeLa (cervical carcinoma) and A549 (lung adenocarcinoma) cancer cell lines. This study is divided into three parts. Firstly, the cytotoxic activity of these compounds was determined by measuring the cell viability of each compound on HeLa and A549 cell lines. The main objective of this analysis is to measure the IC50 value of each compound and determine which compound is best to kill at least half of the cells. Secondly, the effects of programmed cell death and cell cycle were investigated for compounds with the best IC50 for each cell line by using Annexin V-FITC in flow cytometry. Finally, a scratch assay was performed to investigate the effect of these new Isoindole derivatives on cell migration.Master Thesis Investigating Oncogenic Role of Sema6d in Breast Cancer Cells(Izmir Institute of Technology, 2019) Günyüz, Zehra Elif; Yalçın Özuysal, ÖzdenBreast cancer, the most commonly diagnosed cancer type and the leading cause of cancer-associated deaths, is the major health issue among women worldwide. In many cancer types, the expression of the semaphorins and their receptors such as plexins and neuropilins are dysregulated. SEMA6D is a member of class-6 family transmembrane semaphorin proteins and acts through Plexin-A1 receptor. It was previously shown that overexpression of SEMA6D in breast cancer cell line MCF-7 leads to a reduction in proliferation and an increase in migration. On the other hand, in the MDA-MB-231 breast cancer cell line, overexpression of SEMA6D had no significant effect on proliferation but enhanced migration. In this study, we aimed to analyze the effects of SEMA6D overexpression in normal breast cell line MCF10A and investigate the invasive behavior and transformation capacity of SEMA6D overexpressing breast cancer cell lines. We demonstrated that overexpression of SEMA6D leads to elevated proliferation, viability and migration in MCF10A cells, whereas it did not trigger their anchorage-independent growth. On the other hand, MDA-MB-231 and MCF7 cells stably expressing SEMA6D showed reduced colony formation in the soft-agar assay. Furthermore, the invasiveness of MDA-MB-231 cells was elevated with SEMA6D overexpression, whereas SEMA6D overexpression did not stimulate the invasiveness of MCF-7 cells through matrigel microenvironment, whereas slightly trigger invasion through bone microenvironment. In conclusion, SEMA6D overexpression has cell-specific effects on breast cancer. The exact role of SEMA6D in breast cancer development remains undefined and must be further investigated.Master Thesis Determination of Therapeutic Potential of Luteolin for Acute Lymphoblastic Leukemia Cells(Izmir Institute of Technology, 2019) Gürler, Sevim Beyza; Baran, YusufAcute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by increased level of immature lymphoblasts in bone marrow and peripheral blood. The developments of lymphoblasts are genetically/epigenetically inhibited. One of the most common genetic abnormalities in ALL is BCR/ABL translocation which regulates the several pathways related to proliferation, anti-apoptotic and drug resistance through its aberrant tyrosine kinase activity. Although the current treatment strategies include targeting BCR/ABL via tyrosine kinase inhibitors; complete remission, overall survival and mortality of Ph+ ALL patients are still worse as compared to Ph- ALL patients. Therefore, new strategies combined with current treatments are needed for Ph+ ALL patients who are qualified as high risk group of ALL. Different studies showed thatluteolin has anti-cancer and anti-tumor effects on wide range cancer types including breast, colon, lung cancer except ALL in both in vitro and in vivo. In this study, the dose and time dependent cytotoxic, apoptotic and cytostatic effects of luteolin on Philadelphia chromosome +ALL cells were determined for the first time. Besides, the effect of luteolin on cell growth and proliferation of two different healthy cell lines was shown. Moreover, the effect of luteolin on bioactive sphingolipids genes which regulate the several pathways including cell proliferation, apoptosis, drug resistance and senescence in cell was determined in Ph positive ALL cells for the first time. As a consequence, luteolin has cytotoxic, apoptotic and cytostatic effects on Ph positive ALL cells and bioactive sphingolipids genes are regulated in this therapeutic potential by luteolin.Master Thesis Robustness of Fingerprint Verification Algorithms Against Synthetic Deformations(Izmir Institute of Technology, 2019) Cantürk, Sinem; Erdoğmuş, NesliFingerprint recognition is one of the biometric techniques used for the identification of humans. The developments and research about fingerprint recognition to date are of great importance in advancing fingerprint recognition and verification scenarios. The fact that fingerprint recognition systems are used almost everywhere and are easily accessible is directly proportionate to a large amount of research in these areas. During the acquisition of the fingerprint, there are many environmental factors that may affect the quality of the print and eventually, its ability to be recognized. For a fingerprint recognition algorithms, it is important to handle the difficulties that arise due to those variations. The aim of the thesis is to obtain and compare the results of not only an existing feature-based fingerprint recognition techniques but a fingerprint recognition technique that uses deep learning. The main focus is on how fingerprint verification algorithms behave under the circumstances of synthetically distorted fingerprint images. After developing two different verification systems, the goal is to compare system results with and without distorted images. The results of the two methods with and without externally added deformations effect on the fingerprint image is compared. The first system has a feature-based approach comparing the images via local features on the fingerprint. In order to do this two different descriptors that are called ORB and SIFT are used. In the feature-based approach, there is also a matching part and this part is tried with two different matching algorithms that are called Brute Force Matcher and Approximate Nearest Neighbor (ANN) matcher. The second algorithm makes the decision of match or non-match by feeding the raw fingerprint images as an input to a deep neural network and comparing the feature vectors calculated by the network. This study has revealed that deep neural network approach has given more robust and faster results on both the original dataset and distorted versions of the dataset.Master Thesis Natural Ventilation Design for Historic Libraries With Cfd (computational Fluid Dynamics) Simulation(Izmir Institute of Technology, 2019) Gülhan, Özcan; Gökçen Akkurt, Gülden; Erek, AytunçLibraries accumulate and protect written and printed works that make permanent knowledge and cultures have been accumulated throughout human history. Paper-based collections kept in libraries are the heritage of humanity. They are under risk of mechanical, biological and chemical degradation over the years caused by the fluctuations in temperature and relative humidity values and inability to control these values. The aim of the Thesis is to reduce degradation risks on paper-based collections in historic libraries by providing preventive conservation without damaging the structure of the building. The historic Necip Paşa Library which is home for 1147 manuscripts was chosen as a case study. In order to provide preventive conservation for manuscripts, firstly indoor microclimatic data were collected for one year and analyzed to observe the risks that may cause degradation types on manuscripts. Only chemical degradation risk was detected. Window controlled seven natural ventilation scenarios were developed to reduce the risk. Finally, ventilation scenarios were analyzed by Ansys Fluent 17.1. Computational Fluid Dynamics (CFD) modelling was used to observe the effect of natural ventilation scenarios on indoor relative humidity according to outdoor relative humidity and wind direction. Finally, k-? turbulence model was used in CFD analysis. Results shows that during the high chemical degradation risk period (May-October), outdoor air temperature and relative humidity are suitable only 7.53% of the total time which allows appropriate natural ventilation. As a conclusion, natural ventilation is not enough to decrease chemical degradation risk totally for the Library. Therefore, additional mechanical ventilation is required.Master Thesis Hydraulic Design Optimization and Performance Evaluation for a Dishwasher(Izmir Institute of Technology, 2019) Erik, Ömer Berhan; Çetkin, ErdalHydraulic designs of dishwashers with 12 (2 baskets) and 15 (3 baskets) place settings with diverter which distributes the water to bottom and upper spray arms separately were analyzed. First, both hydraulic systems were modeled analytically, so continuous and local losses were calculated based on them. Besides, operating point of systems were determined based on the curve of the pump and head loss. All parameters were also verified by experimental tests. An asynchronous circulation pump (fixed pump rpm and outlet pressure) with the same hydraulic outlet pressure is used in both products. Hydraulic design is evaluated with parameters obtained from the analytical model and then the design of equipment along the hydraulic path was improved. Once parameters improving the designs are determined, modified parts were analyzed numerically with finite volume method. The results were also validated with experimental studies. Lastly, prototype with improved design parameters was produced and installed on a dishwasher. Dishwasher performance index was calculated according to IEC standards to see the effect of new design on dishwasher washing performance. The results show that the energy requirement decreases 25% whereas performance index stays the same.Master Thesis Microscale Precise Position Measurement and Monitoring of Sliding Valves(Izmir Institute of Technology, 2019) Tanrıyapısı, Önder Mahir; Özdemir, Serhan; Özdemir, SerhanIn present study, a sensor, Accuciser, is presented to know the position of sliding valves which have ferromagnetic or diamagnetic guide. The main objective is to develop a sensor, which has low cost and high resolution, that measures the displacement of engine valves or SCR injectors which are used in especially in the automotive industry. For now, the position of the valves, which are using in propulsion systems, or SCR injector cannot be known with a signal from an analog sensor. Instead of analog sensor, the mapping is used from experimental data. However, this mapping gives inaccurate results due to driving style or usage of the system. After seeing the gap in these systems, the sensor was developed, and it fulfils this gap. The sensor is developed based on Faraday’s Law of Induction which was discovered by Michael Faraday in 1830. The sensor consists of two coils and one coil located on top of the other. The most important property of the proposed sensor is working with a direct current. In fact, if the valve is actuated by an electromagnetic force, there is no power consumption on the sensor. The experimental results, for the latter property, are corroborated by theoretical calculations. The output of the sensor is directly proportional to the displacement of the core and it has high signal-to-noise ratio because of the nature of magnetism. The results show that using Accuciser, the proposed sensor, to monitor valve displacement gives more reliable results than current technology.Master Thesis Dynamic Crushing Behaviour of Cactus Geometry Inspired Core Structure(Izmir Institute of Technology, 2019) Balya, Ozan; Taşdemirci, Alper; Güden, MustafaCactus geometry inspired core structure was manufactured with the fused deposition modelling method by a 3D printer using Acrylonitrile Butadiene Styrene (ABS) material filament. The characterization of ABS was made by performing compression tests to take some parameters for numerical models. Numerical preliminary studies were carried out by using the areal density concept and direct-impact Hopkinson pressure bar test method to compare the cactus geometry with the conventional ones in point of the specific energy absorption capacity (SEA). It was understood that from the preliminary work, the cactus inspired structure is intriguing to investigate the dynamic crushing behaviour at least. Quasi-static, drop weight and direct-impact Hopkinson pressure bar tests were conducted to comprehend the energy absorption and crushing behavior in all cases, then to investigate the strain rate and inertia effects on the structure. Implicit and explicit numerical models were made by using LS-DYNA software to validate experiments and to set a precedent for future works. It was seen that the result of numerical models is in harmony with that of experiments excluding the non-fracture structure at the quasi-static implicit model. Moreover, although quasi-static compression gave the structure more stable deformation behavior compared to drop weight impact, higher energy absorption capability was observed on drop-weight tests. In addition, the strain rate effect is more forceful in point of loading carrying capacity compared to the inertia effect despite the fact that it provides the development of buckling and damage formation.Master Thesis Determination of Therapeutic Potential of Apigenin on Acute Lymphoblastic Leukemia Cells(Izmir Institute of Technology, 2019) Uzuner, Erez; Baran, YusufAcute lymphoblastic leukemia (ALL) is a hematological disorder initiating from blood-forming cells of bone marrow. ALL is characterized by the Philadelphia chromosome (Ph) arisen from a translocation between chromosome 9 and 22. This chromosome encodes BCR-ABL oncogene that is a driver regulator. BCR-ABL based studies improved tyrosine kinase inhibitors (TKI) including imatinib, dasatinib, nilotinib, and ponatinib to eliminate this disease. However, the studies on Ph+ ALL patients showed that bioactive sphingolipids have crucial roles in the elimination of the positive effects of these drugs by activating the proliferation-associated pathways, inhibition of apoptosis and increasing drug resistance of the cells treated with these drugs. In this study, therapeutic potential of apigenin, which is a natural flavonoid obtained from celery, parsley and chamomile was investigated on Ph+ ALL cell line, SD-1, and non-cancerous lung cell line Beas-2B. The cytotoxic effects of apigenin on SD-1 and Beas-2B cells were determined by MTT cell proliferation assay. The cell viability analyses on SD-1 cells were conducted by Trypan blue dye exclusion assay following apigenin treatment. Cell cycle and apoptosis analyses including Annexin V/PI-dual staining and JC-1 dye-based mitochondrial membrane potential were examined by flow cytometry. Expression levels of bioactive sphingolipids were determined by RT-PCR and western blot. The cytotoxic analyses indicated that apigenin selectively inhibits the expression of SD-1 cells whereas the IC50 value of apigenin for SD-1 cells has the anti-apoptotic roles in Beas-2B cells. SD-1 cells experience cell death via apoptosis-related pathways and apigenin might arrest the cells at G2/M phases. Indeed, the changes in the expression levels of bioactive sphingolipids genes indicated their roles in apigenin-induced apoptosis in SD-1 cells. This study investigated the cytotoxic and apoptotic effects of apigenin on SD-1 cells and the roles of apigenin in bioactive sphingolipid metabolism for the first time.