Sustainable Development Goal "Goal 3: Good Health and Well-being" ile 'a göz atma
Sayfa başına sonuç
Sıralama Seçenekleri
-
Öge5-fluorourasil için polimer/biyoseramik ve grafen oksit içerikli ilaç taşıyıcı malzeme üretimi ve kinetik çalışmaları(Lisansüstü Eğitim Enstitüsü, 2023-05-04) Kahraman, Ebru ; Saygılı Nasün, Gülhayat ; 506162003 ; Kimya Mühendisliğiİnsan yaşamı için ciddi bir tehdit oluşturan kanser, dünya çapında önde gelen ölüm nedenlerinden biri olmaya devam etmektedir. Dünya Sağlık Örgütü (WHO) tarafından kanserin 183 ülkenin 112'sinde 70 yaş öncesi için birinci veya ikinci ana ölüm faktörü olduğu tahmin edilmektedir. Kanser tedavisi sürecinde karşılaşılan en önemli zorluklardan birisi, uygulanan yüksek toksisiteye sahip ilaçların vücut içerisinde ani ve kontrolsüz salımının, kanser hücreleri dışındaki sağlıklı dokuları da etkileyerek yorgunluk, ateş, saç dökülmesi, deri döküntüsü ve mide bulantısı gibi istenmeyen yan etkilere yol açabilmesidir. Bununla birlikte, biyolojik ortamla ilaç arasında meydana gelen etkileşimler, aktivite ve terapötik etki kaybına neden olarak tedavinin etkinliğini azaltabilmektedir. Bu nedenle, ilaçları uygun terapötik seviyede tutarak yan etkileri azaltmak ve dış etkenlerden koruyarak tedavinin etkinliğini arttırmak amacı ile tasarlanan ilaç taşıyıcı sistem çalışmaları önem taşımaktadır. 5-Fluorourasil (5-FU) ilacı, günümüzde kolon kanseri başta olmak üzere, rektum, göğüs, yumurtalık, pankreas, mide, beyin ve cilt kanseri gibi pek çok kanser türünün tedavisinde yaygın olarak kullanılan bir anti kanser ajanıdır. Bu ilaç, C(Karbon)-5 pozisyonunda hidrojen atomu yerine flor atomu bulunan bir urasil primidini analoğu türüdür. Anti kanser etkinliği oldukça üstün olmasına rağmen, kan plazmasında yarılanma süresi oldukça kısa olan (8-20 dakika) ve kanserli hücreler tarafından seçiciliği olmayan 5-FU ilacı sağlıklı hücreleri de etkileyerek istenmeyen yan etkilere ve tedavi veriminin düşmesine sebep olabilmektedir. Bununla birlikte, düşük molekül ağırlığı ve hidrofilik karakteri, 5-FU ilacının ilaç taşıyıcı sistemlere yüklenme kapasitesinin düşük olmasına neden olmakta ve kontrollü bir salımın sağlanmasına engel oluşturmaktadır. Bu nedenlerden dolayı, 5-FU'nun vücut içerisinde dolaşım süresini arttırabilecek ilaç taşıyıcı malzemelerin geliştirilmesi önem taşımaktadır. Grafen oksit (GO), grafenin oksidasyonu ile elde edilen ve oksijen içeren fonksiyonel gruplara sahip iki boyutlu bir grafen türevidir. Grafene benzer şekilde katmanlı bir yapıya sahip olan grafen oksit; epoksi, hidroksil, karbonil ve karboksilik gruplar gibi oksijen içerikli fonksiyonel gruplar bulundurmaktadır. Bu grupların varlığı, grafen oksite hidrofilik bir karakter kazandırmakta ve biyolojik ortamda çözünürlüğünü arttırarak biyouyumluğunu iyileştirmektedir. Yüksek spesifik yüzey alanı ile birlikte - etkileşimi ve hidrojen bağı oluşumuyla ilaç molekülleri ile etkileşeme geçebilme kapasitesi, grafen oksitin ilaç yükleme ve salım çalışmalarında tercih edilen bir malzeme olarak ortaya çıkmasına neden olmuştur. Bununla birlikte, grafen oksitin vücut içerisinde yalnız başına uygulanması durumunda hücre canlılığında düşüşe sebep olabileceği raporlanmış olup, biyouyumluluğunu iyileştirmek ve mümkün olabilecek toksik etkileri azaltmak için farklı biyomalzemeler ile birlikte fonksiyonelleştirilerek kullanımı tercih edilmektedir. Hidroksiapatit (HAp, Ca10(PO4)6(OH)2), insan vücudu içerisinde diş ve kemik yapısında bulunan, biyoseramik yapılı kalsiyum fosfat bir malzemedir. Biyoaktif, biyouyumlu, yavaş bozunan, osteokondüktif ve osteoindüktif yapısı nedeni ile diş hekimliği, kemik doku mühendisliği alanları başta olmak üzere, ilaç taşıyıcı sistemler ve hücre görüntüleme gibi biyomedikal alanlarda yaygın olarak kullanılmaktadır. Nanoboyutlu hidroksiapatit parçacıklarının farklı kanser hücreleri üzerinde büyümeyi önleyici etki gösterebilmesi nedeni ile, hidroksiapatit içeren kompozit malzemeler kanser ilaçları için geliştirilen ilaç taşıyıcı sistemlerde tercih edilebilmektedir. Bununla birlikte, sert ve kırılgan bir yapıya sebep olmasından kaynaklanan mekanik dezavantajları, hidroksiapatitin tek başına klinik uygulamalarda kullanımını kısıtlayabilmektedir. Ek olarak, yalnızca hidroksiapatitin taşıyıcı malzeme olarak kullanıldığı ilaç salım çalışmalarında yüksek ilk ani salım oranları görülmüştür. Bu nedenlerle, mekanik özellikleri ve kontrollü salımı iyileştirebilecek çeşitli malzemelerin katkısı ile kompozit halinde kullanımı tercih edilmektedir. Jelatin (GEL), kollajenin kısmi hidrolizi ile elde edilen doğal bir polimerdir. Asidik veya bazik prosesler ile elde edilme şekline göre sırası ile A ve B tipi olarak sınıflandırılmakta olup; hayvan derisi, kemik, kıkırdak ve bağ dokusundan elde edilebilmektedir. Düşük immünojenikliği, toksik olmaması, biyouyumluluğu, biyolojik bozunabilirliği ve düşük maliyeti nedeniyle, biyomedikal alanda yaygın olarak kullanılan doğal polimerlerden biri olarak ortaya çıkmıştır. Poliüretan (PU), termoplastik ve termoset polimer sınıfında yer alan, üretimi ve kullanım alanı açısından pek çok çeşidi bulunan bir polimerdir. Yapısal olarak yumuşak parça ve sert parça olmak üzere iki farklı şekilde sınıflandırılan bloklardan oluşan poliüretanlar, moleküler düzeydeki bu parçalı yapıları nedeni ile elastiklik, aşınma dayanımı, kimyasal stabilite ve işlenebilirlik gibi avantajlı özellikler barınıdırmaktadır. Esneklik ve mekanik dayanımın birlikte sağlanabilmesi, poliüretanların medikal alanda kullanımı avantajlı bir malzeme olarak öne çıkmasına neden olmuştur. Bununla birlikte, biyouyumlu ve pH değişimine duyarlı özellik göstermeleri nedeni ile, kontrollü ilaç salım sistemi çalışmalarında kullanımı tercih edilen malzemeler arasında yer almaktadırlar. Yapılan çalışmanın amacı; 5-FU kanser ilacının in vitro ortamda kontrollü salımını sağlayabilecek polimer/biyoseramik ve grafen oksit içerikli ilaç taşıyıcı malzemelerin geliştirilmesi, bu malzemelerin ilaç yükleme ve salım performanslarının araştırılması, deneysel tasarım ve kinetik modelleme çalışmaları ile optimizasyonun yapılmasıdır. Polimer malzemeler olarak jelatin ve poliüretan seçilirken, biyoseramik malzeme olarak hidroksiapatit tercih edilmiştir. İlk olarak, değişen jelatin konsantrasyonları içeren grafen oksit/jelatin (GO/GEL) kompozitleri üretilmiş ve bu kompozitlere adsorpsiyon yolu ile 5-FU ilacı yüklenmiştir. Deneysel tasarım çalışmaları sonucunda, düşük jelatin konsantrasyonu ve pH 8 değerinde 5-FU adsorpsiyonun maksimum olduğu görülmüştür. Adsorpsiyon izotermi çalışmaları sonucunda, 5-FU adsorpsiyonu için en uygun modelin Freundlich modeli olduğu görülmüştür. In vitro salım çalışmaları sonucunda, düşük jelatin konsantrasyonlarında birinci derece kinetik modele ve yüksek jelatin konsantrasyonlarında Higuchi kinetik modeline uygunluk görülmüştür. MCF-7 göğüs kanseri hücre hattına karşılık yapılan MTT testinde 5-FU yüklü GO/GEL kompoziti %22.8'lik bir hücre canlılığı göstermiş, 5-FU ilacının salımını ve etkisini doğrulamıştır. L-929 fibroblast hücre hattına karşılık yapılan MTT testi sonucu,15 μg/ml 5-FU yüklü GO/GEL konsantrasyonlarına kadar %80 hücre canlılığı elde edilmiş ve kompozitlerin biyouyumluluğu doğrulanmıştır. İkinci aşamada, değişen grafen oksit (GO) miktarları içeren grafen oksit/hidroksiapatit (GO/HAp) kompozitleri üretilmiş ve adsorpsiyon yolu ile 5-FU ilacı yüklenmiştir. Deneysel tasarım çalışmaları sonucunda, düşük pH (pH 2) ve düşük başlangıç 5-FU konsantrasyonlarında 5-FU adsorpsiyonu oranının maksimum olduğu görülürken, grafen oksitin hafif bir artışa sebep olduğu görülmüştür. 5-FU adsorpsiyonu için en uygun modelin Freundlich modeli olduğu görülmüş ve maksimum adsorpsiyon kapasitesi (Qm) pH 2.0 koşullarında 36.9 mg/g olarak hesaplanmıştır. In vitro salım çalışmalarında, pH 7.4 koşullarında tüm GO oranlarında salımın sıfır derece kinetik modele uygunluk görülürken, düşük pH değerlerinde ise Higuchi kinetik modele uyum görülmüştür. Üçüncü aşamada, GO/HAp kompozitlerinin 5-FU ilacı için adsorpsiyon yüzdesini iyileştirmek amacı ile, aminlenmiş grafen oksit üretimi yapılmıştır. Aminlenmiş grafen oksit/hidroksiapatit (GO-NH2/HAp) kompoziti sentezlenmiştir ve adsorpsiyon yolu ile 5-FU ilacı yüklenmiştir. GO/HAp kompoziti ile benzer şekilde, GO-NH2/HAp için yüksek GO-NH2, düşük pH ( pH 2) ve düşük başlangıç 5-FU konsantrasyonlarında en yüksek 5-FU adsorpsiyon oranı görülmüştür. Grafen oksitin aminlenmesi işlemi sonrası maksimum adsorplanan ilaç oranında %9.7'lik bir artış belirlenmiştir. 5-FU adsorpsiyonu için en uygun modelin Freundlich modeli olduğu görülmüş ve maksimum adsorpsiyon kapasitesi (Qm) pH 2.0 koşullarında 21.2 mg/g olarak hesaplanmıştır. In vitro salım çalışmalarında, tüm pH koşullarında 5-FU salımı sıfır derece kinetik modele uygunluk göstermiştir. Son aşamada, grafen oksit/poliüretan (GO/PU) kompozit film üretimi yapılmıştır. Poliüretan üretimi aşamasında, biyouyumlu ve ekonomik bir alternatif olan ayçiçek yağı ve hint yağı hidroksil kaynağı olarak kullanılmıştır. 5-FU yükleme işlemi, üretimi aşamasında 5-FU ilacının enkapsülasyonu ile gerçekleştirilmiştir. Deneysel tasarım çalışmaları sonucunda, 5-FU'nun GO/PU kompoziti içerisinden salım yüzdesinin, yüksek pH (pH 10), yüksek GO miktarı ve düşük başlangıç 5-FU konsantrasyonlarında arttığı görülmüştür. Kompozitlerde pH'a duyarlı ilaç salımı gerçekleştiği görülmekle birlikte, yüksek GO içeren kompozit için tüm pH koşullarında, Higuchi kinetik modeline uygunluk sağlanmıştır. Azalan GO miktarlarında ise, salım profilinin sıfır derece kinetik modele uyum gösterdiği belirlenmiştir. Bu tezin bulguları, sentezlenen GO/GEL, GO/HAP, GO-NH2/HAp ve GO/PU malzemelerinin 5-FU kanser ilacı için kontrollü salımı sağlayabilecek biyoyumlu ve ekonomik ilaç taşıyıcı malzemeler olarak potansiyele sahip olduğunu göstermiştir.
-
ÖgeA dynamical systems approach to the interplay between tobacco smokers, electronic-cigarette smokers and smoking quitters( 2020-07) Yıldız, Esmanur ; Özer, Saadet Seher ; Şengül, Mustafa Taylan ; 641335 ; Department of Mathematical EngineeringIn this thesis, the effect of e-cigarettes on smoking cessation is studied using the tools of dynamical systems theory. The purpose here is to examine this efficacy by representing and analysing a non-linear ODE system modelling potential smokers, tobacco smokers, e-cigarette smokers and quitters. Fundamental theories required for the interpretation of the behaviour of dynamical systems are given and some epidemiological models are analyzed. The natural behaviour of some linear physical systems is quite predictable. Contrary to that, many natural phenomena are unpredictable. So, we employ non-linear systems which are more complex and are not exactly suitable for the solution to the problem at hand as opposed to linear systems. Non-linear systems are ubiquitous throughout the natural world. As presented in this work, biological systems can be represented by non-linear systems. For instance, several disease models are generally investigated by using non-linear mathematical models. From a wider perspective, mathematical modelling is significant in describing the smoking cessation models. These models have been examined using ODE systems in view of the fact that we can analyse the spread and control of smoking with these systems. It is well known that smoking is a common social phenomenon in today's world. Since smoking is an addiction, some individuals see the use of electronic cigarette as a way of quitting tobacco smoking. We also know that the prevalence of smoking extremely affects the social behaviour of people in a population.
-
ÖgeA hybrid deep learning metaheuristic model for diagnosis of diabetic retinopathy(Graduate School, 2022-10-17) Gürcan, Ömer Faruk ; Beyca, Ömer Faruk ; 507142109 ; Industrial EngineeringDiabetes is a disease that results in an increase in blood sugar due to the pancreas not producing enough insulin, insufficient effect of the produced insulin, or ineffective use of insulin. According to the International Diabetes Federation 2021 report, approximately 537 million adults aged between 20 and 79 live with diabetes worldwide. It is estimated that the number of people with diabetes will increase to 643 million in 2030 and 783 million in 2045. Diabetic retinopathy (DR) is an eye condition that can cause vision loss, irrecoverable visual deterioration, and blindness in people with diabetes. Today, it is one of the leading diseases that cause blindness. Anyone with any diabetes can become a DR. In ophthalmology, type 2 diabetes can lead to DR if left untreated for more than five years. Diabetes-related high blood sugar leads to DR. Over time, having too much sugar in the blood damages the retina. The deterioration of this disease in the eye begins when sugar blocks the capillaries leading to the retina, causing fluid leakage or bleeding at a later stage. The eye produces new vessels to compensate for the blocked vessels, but these newly formed vessels often do not work well and can bleed or leak easily. DR can lead to other serious eye conditions. For example, about one in 15 people with diabetes develop diabetic macular edema over time. DR can lead to the formation of abnormal blood vessels in the retina and prevent fluid from leaving the eye. That causes a type of glaucoma. It is crucial for people with diabetes to have a comprehensive eye examination at least once a year. Follow-up of diabetes; factors such as staying physically active, eating a healthy diet, and using medications regularly can stop the damage to the eye and help prevent or delay vision loss. Some risk factors increase the development of DR, such as pregnancy, uncontrolled diabetes, smoking addiction, hypertension, and high cholesterol. In addition to being detected by magnifying the pupil in eye examination, DR is also diagnosed with the help of image processing techniques. It is common to use fundus images obtained by fundus fluorescent angiography to detect DR and other retinal diseases. Nowadays, with the increasing number of patients and the developments in imaging technologies, disease detection from medical images by various methods has increased. Deep learning is one of the methods whose application area has increased exponentially in recent years. Deep learning is a subfield of machine learning; both are a subfield in artificial intelligence. Deep learning methods draw attention with their versatility, high performance, high generalization capacity, and multidisciplinary use. Technological developments such as the collection of large amounts of data, graphics processing units, the development of robust computer infrastructures, and cloud computing support the building and implementation of new models.Increasing the number of images for a particular patient case and high-resolution images increases specialists' workload. Diagnosis of DR manually by an ophthalmologist is an expensive and time-consuming process. It requires experts who have remarkable experience. In addition, the complexity of medical images and the variations between specialists make it difficult for radiologists and physicians to make efficient and accurate diagnoses at any time. Deep learning is promising in providing decision support to clinicians by increasing the accuracy and efficiency of diagnosis and treatment processes of various diseases. Today, in some medical studies, the success levels of expert radiologists have been achieved or exceeded. Convolutional neural networks (CNNs) are the most widely used deep learning networks in image recognition, image/object recognition, or classification studies. A CNN model doesn't need manually designed features for training; it extracts features from data directly while network training on images. The automated feature extraction property and their success make CNNs highly preferred models in computer vision tasks. This study proposes a hybrid model for the automatic diagnosis of DR. A binary classification of DR (referable vs. non-referable DR) is made using a deep CNN model, metaheuristic algorithms, and machine learning algorithms. A public dataset, Messidor-2, is used in experiments. The proposed model has four steps: preprocessing, feature extraction, feature selection, and classification. Firstly, fundus images are pre-processed by resizing images and normalizing pixel values. The inception-v3 model is applied with the transfer learning approach for feature extraction from processed images. Then, classification is made using machine learning algorithms: Extreme Gradient Boosting (XGBoost), Random Forest, Extra Trees, Bagged Decision Trees, Logistic Regression, Support Vector Machines, and Multilayer Perceptron. XGBoost gives maximum accuracy of 91.40%. The best potential features are selected from the extracted features by three metaheuristic algorithms: Particle Swarm Optimization, Simulated Annealing, and Artificial Bee Colony. Selected features are classified with the XGBoost algorithm. The metaheuristics significantly reduced the number of features obtained from each fundus image and increased the classification accuracy. According to the results, the highest accuracy of 93.12% is obtained from the features selected with Particle Swarm Optimization. When the study results are compared with the existing studies in the literature, it has shown that this study is competitive in terms of accuracy performance and obtained low features. On the other hand, the proposed model has some advantages; it has a few pre-processing steps, training number of parameters are considerable low, and model can be trained with a small amount of data. This study is one of the first studies showing that better results can be obtained in DR classification by using deep learning and metaheuristic algorithms together. The proposed model can be used to give another idea for ophthalmologists in diagnosing DR.
-
ÖgeA novel antenna configuration for microwave hyperthermia(Graduate School, 2022-11-28) Altıntaş Yıldız, Gülşah ; Akduman, İbrahim ; Abdulsabeh Yılmaz, Tuğba ; 504182309 ; Telecommunications EngineeringBreast cancer affects approximately 2.5 million women each year and the consequences can be fatal. When treated correctly, however, the survival rates are very high. Surgical operation such as lumpectomy or mastectomy are invasive techniques that remove the partial or the whole breast. With early diagnosed cancers and the post-surgical patients, the most used therapy techniques are the radiotherapy, chemotherapy and the use of other anti-cancer agents. The economic and the psychological repercussions may be minimized by the increase efficiency of the treatments. It has been shown that with the artificial hyperthermia, elevated temperature levels at the cancer regions, the effectiveness of these modalities increase. Microwave breast hyperthermia (MH) aims to increase the temperature at the tumor location over its normal levels. During the procedure, the unwanted heated regions called hotspots can occur. The main aim of the MH is to prevent the hotspots while obtaining the necessary temperature at the tumor. Absorbed heat energy per kilogram at the breast, specific absorption rate (SAR), needs to be adjusted for a controlled MH. The choice of the MH applicator design is important for a superior energy focus on the target. Although hyperthermia treatment planning (HTP) changes for every patient, the MH applicator is required to be effective for different breast models and tumor types. In the first part of the thesis, the linear antenna arrays are implemented as MH applicators. We presented the focusing maps as an application guide for MH focusing by adjusting the antenna phase values. Furthermore, these focusing maps put forward the basic principle of focusing the energy at the breast. Sub-grouping the antenna, we obtained two phase main parameters that control the horizontal and vertical focus change. By adjusting these two phase values, we could focus the energy onto the target locations and we showed that with this simple structure, there is no need for optimization methods. However, the linear applicator performance was not successful for some target points, especially when the target is far away from both of the arrays. In the second part of the thesis, we improved the linear MH applicator. We concluded that the reason for the low performance of the linear applicator is mainly due to non-symmetrical geometry of the applicator and the resulting poor coverage. we proposed to radially re-adjust the position of the linear applicator for a better focusing ability while fixing the breast phantom. This generates multiple different applicator scheme without actually changing the applicator design. Particle swarm optimization (PSO) method is used for antenna excitation parameter selection. For the examined two targets, 135° rotated linear applicator gave 35-84% higher T BRS and 21-28% higher T BRT values than the fixed linear applicator, where T BRS stands for the target-to-breast SAR ratio and T BRT stands for the target-to-breast temperature ratio. Not only the rotated linear applicator gave higher performance, but also the circular array is rotated and the results were improved for one target. One of the main results of this study is that, for one target, the rotated linear applicator gave better results than the circular array, which is the state of the art. For the deep-seated target, 135° rotated linear applicator has 80% higher T BRS and 59% higher T BRT than the circular applicator with the same number of antennas. For the other target, the results of the linear and circular were comparable. However, the results obtained with the PSO were not robust. With different initial values (random in our study), the results were very different from each other, and we did 10 repetitions and took the best performing results. In the third part of the thesis, we presented deep-learning based antenna excitation parameter selection method. This method utilizes the learning ability of convolutional neural networks (CNN), rather than searching the solution space from random initial values as PSO does. The data set for CNN training was collected by superposing the electric fields obtained from individual antenna elements. We implemented a realistic breast phantom with and without a tumor inclusion. We used linear and circular applicators to validate the method. CNNs were trained offline with the data sets created first for the phase and then for the amplitude of the antennas. A mask of 1s and 0s is used to define the target region to be focused. This mask was given as the input to CNN models, and the corresponding phase and the amplitude values are calculated within seconds from the CNN models. The proposed approach outperforms the look-up table results, as the phase-only optimization and phase–power-combined optimization show a 27% and 4% lower hotspot-to-target energy ratio, respectively, than the look-up table results for the linear MH applicator
-
ÖgeAçık bilim üniversitelerde neleri değiştirecek?(İTÜ, 2022-02-03) Tonta, Yaşar ; 0000-0003-0285-1338 ; Hacettepe Üniversitesi Bilgi ve Belge Yönetimi BölümüAçık Bilim Üniversitelerde Neleri Değiştirecek? adlı sunumunda akademik iletişim kültüründeki değişimin zorunluluğuna dikkat çekmiştir.
-
ÖgeAesthetic strategies in horror film sound design: Case studies from Japanese horror cinema(Graduate School, 2023-01-17) Akdeniz, Tolga ; Özdemir, Taylan ; 409191110 ; MusicHorror films have a unique place in cinema with their imagery and sonic qualities. While the experience of watching a horror film evolved throughout the years, the fundamental goal of the horror genre is to horrify the viewer in various ways, and it is named after this particular effect it aims to elicit. Sound design plays a major role in creating the horror film experience. In this study the contribution of sound design to aesthetic strategies employed in horror films will be investigated based on case studies from the prolific and influential contemporary horror cinema of Japan. In order to have a better perspective on the conventions of the genre and understand how the selected films converge or diverge from them, the study will be introduced with a theoretical investigation of the horror genre and a historical investigation of Japanese cinema. After the introduction, the properties of film sound in horror films will be examined individually. The analysis method of this study relies both on measurable data with objective observations and also subjective observations based on the phenomenological experience of horror films. The introduction of the analysis is by examining the atmosphere of horror films, although a vague and an intangible phenomenon, it is a crucial quality that affects the perception and it relies heavily on music and sound design. The framework of the analysis consists of 3 major components based on the theories of Michel Chion (1994), the functional properties of film sound: Anticipation, punctuation, unification and separation. The analysis methodology developed by Taylan Özdemir (2015) based on the physical, spatial and temporal properties of film sound will be utilized to gather and interpret measurable data within these functional properties of film sound. The anticipation function of film sound investigates how sound is employed in order to create and build tension, to create suspense. The punctuation function of film sound is investigated under four categories, these are cinematic shock, sonic emphasis for narrative cueing, silence for emphasis and somatic empathy. While cinematic shock focuses on the abrupt startling moments of horror films, somatic empathy explores how horror films affect the body of the viewer. In the last part of the individual analysis, how film sound contributes to achieving spatial, temporal or atmospheric unification and separation is investigated. In the final section of the study, the developed analysis methodology will be utilized to examine the selected scenes in detail. In conclusion, in this study the previously developed analysis methodologies will be further expanded to horror cinema; and the sonic aesthetic strategies employed for the intended horror film experience and how these emerge in Japanese horror cinema will be investigated.
-
ÖgeAntenna and measurement system for microwave imaging of breast tumors(Institute of Informatics, 2015) Abbak, Mehmet ; Akduman, Ibrahim ; 705092006 ; Satellite Communication and Remote SensingWith the increasing demand for better medical imaging technologies, different medical screening procedures become a research topic for scientific community. One of the important challenges in today's medical imaging is surely the early detection of breast cancer. The breast cancer is one of the very dangerous health threat for women. This disastrous illness is observed approximately one in eight women by the age of ninety years old. The likelihood of successful treatment increases with early detection of breast cancer increases. Up to now, X-ray tomography is the golden standard for characterizing and detecting the breast cancer. In contrast to this fact, X-ray mammography has significant disadvantages. These disadvantages trigger a search for different imaging modalities, which can be integrated with currently available imaging technologies. Microwave imaging is one of those newly emerging solutions. The use microwaves in the early detection of breast cancer is motivated by several reasons. First of all, it is shown that the electrical properties of the malignant and normal tissues are substantially different, which can be easily revealed by microwave imaging. Moreover, microwaves can easily penetrate into breast tissue at a few GHz ranges. Considering that the dimensions of the breast is comparable with the wavelength at those frequencies, the malignancies can be detected from the scattered field by means of nonlinear inverse scattering algorithms. Nowadays, there are many different studies to design microwave imaging systems for the early detection of the breast cancer. An inevitable part of these systems is the nonlinear imaging methods. With the recent developments in computer technology and the newly introduced efficient algorithms, these methods are now employed in any microwave imaging system. However, the quality of reconstructed images produced by these methods is closely connected with the scattered field data that is acquired by the microwave antennas. Hence, one of the most important parts of the microwave imaging systems is the transceiving antennas. It is shown that, regardless of the method in the hand, the resolution of the produced images increases with the increasing signal-to-noise ratio (SNR) and with the increasing sampling density of the field. To increase SNR, the designed antenna must have higher gain levels together with a lower back-to front ratio level; whereas the sampling density of the field increases when the dimensions of the antenna gets smaller. Furthermore, the microwave imaging methods require certain preprocessing steps, which accept only a single polarization of the incident field as input. Thus, the designed antennas must be highly linearly polarized. Finally, the microwave imaging of the malignancies is a highly ill-posed inverse problem. Thus, the frequency diversity in the scattered field data must be as high as possible. Consequently, today's microwave breast cancer imaging systems require high gain, linearly polarized, wide-band and compact antennas as their scattered field sensors. In this context, the first contribution of this thesis is the design of a cavity-backed Vivaldi antenna (CBVA) for microwave breast measurements. The design criteria for the antenna is shaped by the requirements of the free-space measurement scenario where the receiving and the transmitting antennas are rotated by a mechanical scanner. Later, various breast phantom measurements is conducted with the CBVA to reveal its feasibility for microwave tomography. As the second contribution, a novel Corrugated Vivaldi antenna (CVA) is proposed. The main idea is opening corrugations on the edge of the antenna to decrease the induced currents, which can degrade the performance. Doing so a design with better properties such as higher gain, smaller beam width, lower back-to-front ratio is obtained. The characteristics of the obtained CVA is measured in a detailed manner. Furthermore, the imaging performance of the introduced design is compared with a generic Vivaldi antenna (VA) of the same size. For this purpose, several experimental configurations are prepared in an anechoic environment and scattering parameter (S-parameter) measurements are obtained for those setups by means of the both antennas. Acquired S-parameters are then employed in a recently proposed qualitative imaging method, the S-parameter based Linear Sampling Method (S-LSM), which is a more suitable form of Linear Sampling Method (LSM) for real world applications. Experimental results show that the proposed design performs better than VA in such real world microwave imaging problems.
-
ÖgeAn assessment of building information modeling (BIM) implementation for the Turkish transportation infrastructure industry(Institute of Science and Technology, 2020-07) Yiğiter, Feyza ; Atahan, Ali Osman ; 633458 ; Ulaştırma MühendisliğiTransportation infrastructure, which includes highways, railways, bridges, airports, and tunnels, is an integral part of the socio-economic development of a country. There is a great need for innovative techniques and technologies that increase productivity and efficiency in terms of time, cost, and quality for the design, construction, operation, and maintenance of transportation structures due to the growing population and the increasing demand for transportation. Building Information Modeling (BIM), an innovative technology widely adopted in the construction industry, has the potential to revolutionize the transportation infrastructure industry due to the knowledge-based nature of transportation infrastructure projects. BIM enables the creation of a 3D object-based and parametric model of a structure, and the BIM model supports collaborative working and interoperability among all disciplines via a digital information-sharing platform. It aims to ensure that all the information generated through the lifecycle of a project is accurately and efficiently stored, shared and used, thereby to make the decision-making and problem-solving processes easier, quicker and more accurate based on the information, and ultimately to minimize the possible time, cost and quality losses of the project. While the initiatives and investments are increasing in Turkey, as with the other countries in the world, BIM is not widely implemented in the Turkish transportation infrastructure industry.
-
ÖgeBioactive peptide encapsulation by electrospinning technique: Characterization of electrospun fibers and mathematical modelling of release kinetics(Graduate School, 2023-06-12) Kırbaş, Zahide ; Altay, Filiz ; 506152509 ; Food EngineeringBioactive peptides, which are biologically active amino acid groups in the sequence of proteins, exhibit a variety of beneficial effects including antioxidant, anti-inflammatory, antihypertensive, anticancer, antidiabetic, antimicrobial, antithrombotic, hypocholesterolemic, antiaging and opioid activities as well as prevention of cancer, osteoporosis, hypertension, cardiovascular disorders and neurodegenerative diseases such as Parkinson and Alzheimer's diseases. However, the bioactive peptides isolated from plants and animals may be lost during processing and storage. Furthermore, bioactive peptides have short in vivo half-lives, low bioavailability and poor stability against gastrointestinal conditions. Therefore, to use of encapsulation technologies such as coacervation, ionic gelation, electrospraying, microfluidic, emulsification, liposomal encapsulation, spray drying and electrospinning have been started to become widespread. Considering the above, the objectives of this Ph.D. thesis were (i) to produce a nanofibrous delivery vehicles for bioactive peptides without using any synthetic polymers or any hazardous solvents by using electrospinning, to characterize electrospun fibers to evaluate the effect of formulation and properties of feed solutions on electrospinnability and to examine the encapsulation efficiencies of produced nanofibrous delivery vehicles by using a model peptide; (ii) to produce carnosine (Car) loaded water-in-oil-in-water (W1/O/W2) double emulsions with different formulations using as feed emulsions in emulsion electrospinning study; (iii) to produce carnosine (Car), an antioxidative peptide, loaded pullulan (Pul)-sodium alginate (NaAlg) based composite nanofibers by uniaxial (blending), coaxial and emulsion electrospinning techniques and to characterize electrospun fibers to evaluate the effect of solution /emulsion properties and the role of emulsion parameters; (iv) examining the encapsulation efficiencies of electrospun fibers and to investigate the effect of encapsulation on antioxidant activity of Car; to determine the effects of electrospinning encapsulation and crosslinking on release behavior of carnosine from electrospun nanofibers during in vitro digestion and to analyse the release kinetics by establishing corresponding mathematic models.
-
ÖgeBiopolyester / natural polymer blends for biomedical applications(Graduate School, 2022-05-22) Turan, Cansu Ülker ; Güvenilir, Yüksel ; 506152001 ; Chemical EngineeringIn this thesis, it is aimed to fabricate an antibiotic delivery system with optimal release kinetics that will overcome this problem. In recent years, fabrication of biocompatible electrospun nanofibers for drug delivery applications is the subject of increased interest, since they mimic the extracellular matrix, provide high surface area, and controlled drug release. In the present study, natural polymers (gelatin or both gelatin and chitosan) were blended with enzymatically synthesized biopolyester, poly(ω-pentadecalactone-co-ε-caprolactone) copolymer (PDL-CL), in order to obtain a synergetic effect. By the use of synthetic and natural polymers together, it was aimed to combine well-defined degradation and mechanical properties of a synthetic polymer with biocompatibility, cell adhesivity, and ability of site-specific delivery due to their functional groups of natural polymers. In this way, PDL-CL/gelatin and PDL-CL/gelatin/chitosan nanofibrous membranes were fabricated for controlled delivery of tetracycline hydrochloride (TCH) which is a commonly preferred antibiotic for treatment of skin infections resulted from a cut, burn or surgical operation. PDL-CL copolymer was synthesized by the catalysis of a home-made immobilized enzyme, Candida antarctica lipase B (CALB) immobilized onto rice husk ashes (RHA) via physical adsorption. Lipase-catalyzed copolymerization studies are limited and there is an increasing interest to improve material features by this way. Moreover, utilization of an enzymatically synthesized polymer rather than a polymer synthesized by organometallic catalysts in a formulation that will be used for a biomedical application may be advantageous, since the resulting product will be metal-free. Electrospinning of an enzymatically synthesized polymer is a challenging issue due to their low molecular weights, therefore studies that cover fabrication of electrospun nanofibrous drug delivery systems using an enzymatically synthesized polymer are limited in literature.
-
ÖgeClinical assessment of the microwave imaging system forbreast cancer screening and early detection(Graduate School, 2023-04-26) Janjic, Aleksandar ; Çayören, Mehmet ; Akduman, İbrahim ; 504182310 ; Telecommunication EngineeringFemale breast cancer has surpased lung cancer, as the most diagnosed cancer in women population, with around 2.3 million cases arising each year. If diagnosed in late stages, it can be highly lethal, with the survival rate of only 25%. Thus, detecting the cancer in an early stage can have a major impact on decreasing the death rate of the patients. Nowadays, mammography is considered as a gold standard for breast cancer screening and diagnostics. Beside mammography, ultrasound, and magnetic resonance imaging can be used to detect the cancer. However, there are several risk factors that are limiting mentioned imaging modalities, such as: ionizing radiation exposure, pain induced by breast compression, overdiagnosis, false-positive examinations, falsenegativity in dense breasts, operator dependancy, prolonged procedures, high hospital costs, and special facility requirements. Microwave breast imaging emerged as a promising novel imaging technology that can, potentially, contribute to the field of breast cancer early screening and diagnostics, mostly because of its non-ionizing and non-invasive nature. Harmless radiation offers the opportunity of frequent scanning, even for the women of an early age, such as 18. Early-age and routine tests are crucial, especially for women with hereditary genetic mutations, where there is a considerable risk of breast cancer appearance. Beside its non-ionizing, and non-invasive nature, microwave imaging offers fast and painless scans, which can significantly increase the number of breast check-up tests, consequently increasing the number of detected early-stage cancers. Consequently, microwave breast imaging can have can substantially impact on the long-term breast cancer survival rate. The technology itself utilizes the difference in electromagnetic properties of healthy and cancerous tissue, as well as the dielectric difference between different type of cancerous tissues (benign or malignant), to detect the presence of anomalies inside the patient's breast and provide their pathology. In the first part of the thesis, we integrated inverse scattering algorithm to acquire the microwave images, and provide information about breast cancer location (detect the breast cancer), from the data collected with the microwave breast imaging device, namely SAFE, developed by the joint work of Mitos Medikal Technologies A.S. and the Medical Device Research, Development, and Application Laboratory of Istanbul Technical University. Dataset used in the study (scans from 115 patients), was acquired through the clinical trials performed by the Marmara University School of Medicine. In addition to the breast lesion detection, we analyzed the effect of the factors of interest, such as: breast density and size, tumor size, as well as patient's age, on the SAFE clinical capabilities. Results show, that we were able to detect 63% of breast lesions, where the breast size had a high impact on the overall score. Significantly lower number of lesions were detected in smaller breasts (51%), compared to the large ones (74%). Density also influenced our inverse scattering approach, as the overal rate of 76%, we achieved in fatty breasts, decreased to 56% in dense breasts. Second part of the thesis is reserved for the machine learning approach, namely adaptive boosting, we implemented on the SAFE dataset, to classify breast lesions, based on their pathology. We used the same dataset as in the first part of the thesis. As in the previous study, we analyze the effect of breast density and size, tumor size, and patient's age, on the used data. In addition, we perform statistical analysis (two-sample t-test) to determine if the difference between the benign and malignant dataset exists. In the existing dataset, 70 benign, and 43 malignant lesions were present. We exclude two cases, due to the unknown pathology. Our machine learning approach achieved the accuracy of 78%, sensitivity of 79% and specificity of 77%. The results indicate that we were able to classify both, benign and malignant lesions, at similar rate. Participant's age was the only factor that highly affected our approach outcome, where the overall rate (accuracy) of the device in young patient group was 84%, compared to the 76% achieved in older patient group. In the third part of the thesis, we implement another machine learning approach, namely Gradient Boosting, to distinguish benign from malignant lesions, considering new dataset, acquired from latest SAFE clinical trials. Additionally, compared to the previous studies, we changed the measurement unit component of the device. Fiftyfour patients were analyzed, where 29 of them had benign, and 25 malignat findings. As in the previous study, we apply statistical analysis (two-sample t-test), to determine if the difference between the benign and malignant dataset exists. Sensitivity, specificity and accuracy we achieved were 80%, 83% and 81%, showing that, in this study as well, we were able to classify both benign and malignant lesions at similar rate, despite of the hardware and software changes implemented. Contrary to the previous studies, multiple factors (breast size, density and age) affected our approach outcome. We achieved significantly higher accuracy in larger breasts (86%), compared to the smaller ones (78%). Additionally, accuracy acquired in dense breast (67%) was significantly lower than in fatty ones (93%). At the end, our method accuracy was 88% in older patient group, compared to the 71% in younger group.
-
ÖgeComposite nanofiber patches for topical drug delivery systems(Graduate School, 2021-04-19) Barbak, Zarife ; Karakaş, Hale ; 503122805 ; Textile Engineering ; Tekstil MühendisliğiNanofibers are ultrafine, continuous, solid state textile fibers that have diameters less than 1 micrometre. Nanofibers possess remarkable properties such as high interconnected porosity, specific surface area, ability to imitate the Extra Cellular Matrix (ECM) and potential carrier for drug delivery. Due to these fascinating properties, nanofibers are attractive candidates for medical applications for instance wound dressings, tissue scaffolds and artificial blood vessels. Electrospinning is the simplest and most practical among all methods to produce fine fibers with diameters ranging from micrometres to nanometres. Basic electrospinning equipment includes a high voltage source, a solution feeding unit, a syringe with a tip and a collector. At first, high voltage is applied to the polymer solution to produce an electrical field between the tip and the collector to shape the droplet on the tip as Taylor Cone. When the electrostatic force is higher than the surface tension of the polymer solution, polymer jet is ejected from the tip to the collector. Then, polymer jet reaches to collector following a spiral way by getting longer and thinner. Finally, nanoscale fibers are obtained on the collector. Topical drug delivery systems are composed of a formulation that applied to the skin directly to heal disorders or disease of the skin which guide/target pharmacological effect of the drug to the skin surface. Different pharmaceutical dosage forms can be used in topical drug delivery such as gels, creams, ointment, liquid preparation, sprays and solid powders. Electrospun nanofibers are excellent materials for drug delivery systems due to high interconnected porosity, high surface area, ability to imitate the Extra Cellular Matrix (ECM), potential carrier for drug delivery. Utilization of nanofibers in drug delivery systems is based on the principle that the high surface area of the nanofibrous formulation increases the dissolution rate of the drug. Compared with other dosage forms such as; liposomes, micelles and hydrogels, major advantages of nanofibers are increment in drug loading efficiency and loading capacity, low systemic toxicity and excellent stability. Furthermore, several drugs can be carried within nanofibers with high local drug concentration due to their excellent targeting and drug transportation ability in a safe way. Electrospinning offers the opportunity for direct loading of drugs or biological agents for instance antibacterial molecules, antibiotics, enzymes, growth factors, proteins, peptides, vitamins, DNA into the electrospun nanofibers. Poly (ε-caprolactone) (PCL), Poly Lactic Acid (PLA) and Poly (ethylene oxide) (PEO) were used as carrier polymers for drug delivery. PEO is a highly aqueous soluble polymer, that interacts with the body fluid quickly due to its hydrophilicity resulting in dissolution. PEO is widely used in the polymer matrix to enhance bioavailability and solubility of drugs because of its high aqueous solubility and unique properties in drug delivery applications. The compatibility of PCL and PLA with different types of drugs enables uniform drug distribution in the polymer matrix and the slow degradation rate makes them favourable for prolonged drug delivery systems. In recent years, various studies were reported on the fabrication of drug delivery systems, generated by electrospinning of PCL, PEO, PLA and their blends. PCL, PEO, PLA nanofibers or their blends were loaded with different drugs and biological agents such as; Niclosamide, Silver nanoparticles, Vitamin B12, Curcumin, Lysozyme, AgNO3, Metronidazole (MNA). Polymer blending is an effective approach to prepare functional nanofibers by incorporating the favourable properties of the component polymers. Furthermore, polymer blending facilitates the manipulation of physical, mechanical or biochemical properties of nanofibers. Hydrophilic/hydrophobic polymer blends have been electrospun into nanofibers to fabricate controlled DDS. The hydrophobic polymer forms the backbone structure and it degrades slowly, creating a long term but steady-state drug release. On the other hand, the hydrophilic polymer degrades with a more rapid process, faster than hydrophobic, which accelerates the drug release. In this study, hydrophilic water-soluble PEO was selected for the polymer matrix to enhance the solubility and bioavailability of insoluble SSD. The hydrophobic character of PCL and PLA offers a long period SSD release therefore hydrophilic PEO was blended with hydrophobic PCL and PLA. Thus, PCL/ PEO and PLA/PEO composite polymer matrix was used to provide both increased solubility and controlled release of SSD. Silver sulfadiazine (SSD) is a non-ionized, water-insoluble, topical agent with a wide range of antimicrobial activity that is affected both on bacteria and fungi. SSD is a sulfonamide based drug that is formed by the reaction of sulfadiazine with silver nitrate to form complex silver salt. SSD is used extensively in the topical treatment of infected burns. Silver sulfadiazine provides a long-term release of silver ions, whereas in the case of other silver salts, such as silver nitrate, large amounts of silver ions are released all at once. Thus, the use of SSD decreases the need for frequent application. This makes SSD a desirable and favourable agent since the frequent application is not always practical or possible for patients. However, the low aqueous solubility (3.4 mg/l at pH = 6.8) restricts the drug efficiency, bioavailability and potential antimicrobial activity of SSD thus its applications are limited. Drug solubility is an important issue since efficient drug release and antimicrobial efficiency is contributed just by decomposition of SSD to sulfadiazine and silver ions. Also, the solubility problem of SSD makes it difficult to be stabilized and incorporated into the polymer matrix. The aim of the thesis is to produce a novel SSD loaded topical drug delivery system by using advantages of electrospun nanofibers. Also, a new buffer, Water/Propylene Glycol/ Phosphoric Acid (82:16:2) was utilized to investigate the dissolution and release behaviour of SSD. Thereby SSD containing PCL/PEO and PLA/PEO composite nanofiber carriers were electrospun to achieve the enhancement in solubility, effective drug release and efficient drug loading of SSD. For this purpose, initially, the water-insoluble SSD was incorporated into highly aqueous soluble PEO to increase the solubility. Afterwards, the PEO+SSD solution was blended with PCL and PLA solution to produce composite PCL/(PEO+SSD) and PLA/(PEO+SSD) nanofibers and PCL/(PEO+SSD) casting films for topical drug delivery. SEM method was used to enable the observations of fiber defects and irregularities in the nanofibers structures and to measure the average fiber diameters of the nanofibers. The morphological characterization of the casting films was carried out by SEM and Optical Profilometer. Energy dispersive spectra (EDS) analysis was performed to confirm that the composite nanofibers and casting film which contain SSD, by detecting the Silver (Ag), Nitrogen (N), Sulphur (S) content of the nanofibers. Moreover, EDS-Mapping was carried out to show the distributions of these elements in the composite nanofibers and casting films. The stability of SSD in the fiber structure and the molecular interactions in the drug-free and drug loaded nanofibers were examined by Attenuated Total Reflectance Infrared (FTIR-ATR) Spectroscopy. The crystalline structure of the SSD loaded composite electrospun nanofibers were investigated with X-ray diffraction (XRD) analysis. Atomic Force Microscopy (AFM) was used to determine the surface roughness of the composite nanofibers. 3D AFM Images show the roughness structure of nanofibers. Water contact angle measurements were performed to evaluate the wettability properties of the fabricated nanofibers and casting films surfaces. In vitro drug release media and release conditions were optimized and the controlled drug release profile was obtained for 24 hours. Drug loading efficiency of the nanofiber formulations and casting film were calculated. To understand the SSD drug release mechanisms from SSD loaded formulations; Zero Order, First Order, Higuchi, Hixon Crowell and Korsmeyer-Peppas kinetics models were applied in the drug release profiles of the formulations. Drug release studies were also verified with conductivity measurement due to the conductive nature of SSD. Antibacterial activities of the composite nanofibers against gram-positive Staphylococcus aureus (S. aureus) and gram negative Pseudomonas Aeruginosa (P. aeruginosa) Escherichia coli (E. Coli) bacteria were performed for the period of 24, 48 and 72 hours according to disc diffusion test method. Also, the antibacterial activity of commercial SSD cream was tested for comparison with nanofiber formulations. Furthermore, antibacterial activity of the SSD loaded PCL/PEO and PLA/PEO nanofibers were examined with determining MIC and MBC values. Stability studies of the composite nanofibers were done for 3 and 6 months periods. Nanofiber samples were kept both at refrigerator conditions (+4ºC) and room conditions (25ºC ±2 and 65 % ±2ºC relative humidity) to evaluate stability of nanofiber patches. Stability tests were performed with calculating drug loading amount, cumulative drug release by UV absorption measurements and analysing surface morphology by SEM analysis. Finally, the cytotoxicity studies of the drug loaded and drug-free PCL/PEO and PLA/PEO nanofiber patches were done with using the cell viability assay (MTT assay).
-
ÖgeControlled delivery of chalcone via biopolyester nanohybrid(Graduate School, 2022-11-17) Kaptan, Yasemin ; Güvenilir, Yüksel F ; 506162010 ; Chemical EngineeringIn recent years, biodegradable, biodegradable polymers have received great attention especially in medical applications and have begun to replace traditional petroleum-based synthetic polymers. Durable polymeric materials with superior physical, mechanical and chemical properties are highly demanded for medical applications. It is crucial that these materials can survive and perform in the harsh conditions of the human body, such as very low or very high pH environments and mechanical stress. One approach to manufacturing such advanced medical devices is the use of hybrid polymeric materials. In simple terms, a hybrid polymer is material consisting of two compartments, one of which is a natural or synthetic polymer, interacting with each other at the molecular level. The formation of an organic/inorganic hybrid system allows us to take advantage of the advantageous properties of each component or to create enhanced properties, sometimes synergistically. Especially in drug delivery and controlled release applications, several inorganic materials such as iron oxide nanoparticles, gold nanoparticles, silver nanoparticles, mesoporous silica and various types of clay are widely used either individually or in combination with polymers. These inorganic materials are preferred because of their small particle sizes and improved optical, electrical and mechanical properties. Despite the superior properties of inorganic materials, the use of such inorganic particles as drug carriers has some drawbacks. The main disadvantage is that they require surface modifications to ensure stability and good dispersion. Generally, these inorganic particles are used in drug delivery applications by coating or grafting with biodegradable and biocompatible polymers or forming composites. This approach also increases the biocompatibility of particles, which is one of the key features in the development of successful drug delivery system. These polymers can be synthetic or natural, and the most commonly used polymers in organic/inorganic hybrid systems for medical applications are polycaprolactone, polyvinyl alcohol, poly(d,l-lactide-co-glycolide), polyethylene glycol. Organic/inorganic hybrid systems developed with a polymer and inorganic particles can be classified under two main groups depending on the interactions between the two components. In Class 1 hybrid systems, inorganic particles are trapped or encapsulated in the polymer matrix by weak intermolecular forces such as Van der Waals, electrostatic interactions, and hydrogen bonding. Class 2 organic/inorganic hybrid system is formed by covalent or ionic bonding between organic and inorganic components. This covalent bonding can be formed by two different approaches: polymer in situ synthesis in the presence of inorganic particles, in situ formation of inorganic material, or a combination of polymer and inorganic material, both of which are produced ex situ. Interface characteristic is an important factor that changes the characteristics of the developed hybrid system. PCL has high biocompatibility as its degradation products can be metabolized in the body or excreted directly from the body. Because of its biodegradability and biocompatibility, PCL has been approved by the US Food and Drug Administration for use in medical applications. PCL-based materials have been successfully used in bone tissue regeneration, skin tissue engineering and vascular tissue engineering applications. In addition, several drug release studies using PCL-based drug delivery systems have been reported. PCL can be synthesized both chemically and enzymatically via ring-opening polymerization (ROP). Industrially, tin octoate is used as a metallic catalyst. Metallic catalysts operate at high temperature and pressure. Also, the end product may be toxic due to unremoved metallic residue, thus reducing the chances of PCL's medical applications. On the other hand, enzymes are non-toxic and can catalyze reactions in milder conditions. Lipase enzymes catalyze the polymerization of ε-caprolactone (CL). Drug delivery system (DDS) designs improve drug pharmacokinetics and biodistribution and provide a sustained release profile. DDS provides some exceptional properties compared to conventional drug formulations. The major disadvantage of active substances used in the treatment of diseases is that some molecules agglomerate in body fluids due to their hydrophobic character. Conventional drug formulations provide a solution to this complexity by using appropriate additives. However, these additives can have adverse effects on their intended site of action. The drug carrier used in such designs also protects the targeted area from the toxic effects of active molecules by controlling the dosage and keeping it below the toxic limit. Another function of the carrier material is to protect active molecules from premature degradation and rapid degradation by body metabolism. Smart drug delivery systems (SDDS) are systems designed and developed to deliver active substances to the desired site of action and to release them when stimulated by a physical or chemical change. The main purpose of using SDDS is to control the release kinetics so that the active material can be delivered to the desired site of action without causing any side effects to the non-targeted sites. Controlled release of the active ingredient is usually provided by stimuli-responsive polymers. Such polymers can undergo structural changes when exposed to different physical conditions that facilitate drug release. These changes in the physical environment, or 'stimulants', can be light radiation, temperature, pH, and magnetic stimuli. Chalcones are open-chain molecules naturally found in plants. Their chemical structure consists of two aromatic rings with a three-carbon α,β-unsaturated carbonyl system between them. The chemical structure of chalcones can be varied by adding functional groups to aromatic rings. Trans-chalcone (TC) has attracted attention in recent years in terms of its biological activities, due to its abundance in nature, its preparation and its simple structure. TC has been proven to have anticancer activity against several types. The anti-leishmania activity of trans-chalcone has been widely studied. TC is also anti-inflammatory and acts by reducing oxidative stress caused by various inflammatory diseases. However, there are limitations to the clinical use of TC, mainly due to its water-insoluble and thus low bioavailability. TC is a plant-based chemical, so its toxicity in the body is relatively low compared to synthetic drug molecules. However, one extremely risky aspect of TC accumulation in the body is that TC is a proestrogen. TC is metabolically activated to many other chemicals. These compounds have been shown to have estrogenic activity. Many adverse health effects may occur in mammals due to this estrogenic activity of xenobiotic compounds, such as precocious puberty in females, obesity, decreased sperm count, changes in reproductive organs and sexual behavior, and an increase in certain types of cancer. Therefore, it is very important to control the dosage of TC therapy and prevent the accumulation of TC molecules in the body. This study aimed to synthesize a new hybrid polymer based on PCL and silica particles with low crystallinity and hydrophilic character. The synthesis reaction was in situ ring-opening polymerization of ε-caprolactone catalyzed by immobilized Candida antarctica Lipase B. In this study, the free form of Candida antarctica Lipase B was immobilized on rice husk ash by physical adsorption. The specificity and stability of CALB were increased by providing enzyme immobilization. The support material on which the enzyme was immobilized was first prepared by burning rice husks in an oven at 650 °C for 6 hours. The produced RHA is a material with a high silica content, which plays a very important role in the formation of the nanohybrid system in the next steps. In order to add functional groups that will facilitate enzyme adsorption to the RHA surface, the surface was modified using four different organosilane compounds, 3-APTES, 3-APTMS, 3-GPTMS and 3-TMSPDA, before enzyme immobilization. Results from the analysis of TGA curves found that different organosilane compounds behave differently. Surface modification percentages were calculated as 1.2%, 0.8%, 3.7% and 10.1% for 3-APTES, 3-APTMS, 3-GPTMS and 3-TMSPDA, respectively. This reaction took place through the –OH groups of RHA and the methoxy or ethoxy groups of the silanization agents used, and Si-O-Si bonds were formed. After CALB immobilization on surface modified RHA, the resulting catalytic systems were used to catalyze the ROP of ε-caprolactone and to synthesize PKL-based nanohybrid systems in situ. During this reaction, short PCL chains were grafted from the free –OH groups of surface-modified RHA as well as the long, aliphatic chains of pure PCL. Therefore, it is very important to keep the surface modification at an optimum level in order to achieve PCL grafting from silica. Evidence from this analysis shows that increasing the percentage of silanization by a given amount increases the grafting efficiency. Previous studies suggest an inverse relationship between PCL chain length and the number of surface Si-OH groups. The findings of this study are in line with those of previous studies that suggested the role of silanol groups as co-initiators for the polymerization reaction resulting in a high number of growing chains. A significant decrease in the percentage of crystallinity was observed for all nanohybrid samples, which was associated with low molecular weight and inhibition of crystal formation by silica in the nanohybrids. Also increased glass transition temperature due to restricted mobility caused by grafted PCL. PCL-based nanohybrids were hydrophilic. The hydrophilic character of nanohybrids can markedly increase the bioavailability of poorly water-soluble drug molecules. The second aim of this study is to develop TC-loaded microspheres with O/W emulsion and nanospheres with interfacial polymer deposition method and to investigate the loading efficiency and in vitro release behavior.PCL-based nanohybrids synthesized in the first part of this study were used as polymeric carriers in these drug delivery systems. The result of this research showed that there are optimum microsphere formulations with 60-75% encapsulation efficiency. One of the more important findings from this study is that TC release was prolonged in a controlled manner to 22-57 days. It is an important property of our hydrophilic microspheres as it can increase the bioavailability of poorly water-soluble TC. Similar results were obtained with TC-loaded nanospheres produced by interfacial polymer deposition or nano-deposition method. Higher encapsulation efficiency (80-83%) was obtained with nanospheres. TC release from the nanosphere formulation was increased relative to the microsphere formulations; cumulative emissions reached 83-90%. The nanospheres showed pH-dependent release behavior; the acidity of the release medium increased the release. The TC release has been extended to 28 days under neutral conditions. Water contact angle measurements also revealed the hydrophilic character of the nanospheres.
-
ÖgeDeep learning approaches for multiple sclerosis lesion segmentation using multi-sequence 3D MR images(Graduate School, 2023-03-30) Sarıca, Beytullah ; Şeker, Dursun Zafer ; 706142007 ; Geographical Information TechnologiesMultiple Sclerosis (MS) is a chronic inflammatory, immune-mediated, neurodegenerative, and demyelinating disease that impacts the Central Nervous System (CNS). The disease can cause permanent damage or deterioration (demyelination) to the nerves in the CNS. This damage results in the formation of lesions or plaques in the nervous system, leading to a wide range of symptoms such as problems with vision, loss of coordination, muscle weakness, and cognitive impairment. Early diagnosis and monitoring of MS are crucial since diagnosing the disease in its advanced stages can be more challenging. Therefore, effective methods for diagnosing and monitoring MS in its early stages are needed to improve patient quality of life and treatment outcomes. Magnetic Resonance Imaging (MRI) is widely used for monitoring, measuring, detecting, and characterizing MS lesions. T1-weighted (T1-w), T2-weighted (T2-w), and Fluid-Attenuated Inversion Recovery (FLAIR) sequences are commonly exploited in MS diagnosis as they provide different information about the brain tissues and the presence of lesions. Thereby, MRI is a useful tool for diagnosing and monitoring MS. Recently, Deep Learning (DL) methods have achieved remarkable results in the automated segmentation of MS lesions from MRI data, potentially improving the accuracy and efficiency of MS diagnosis and monitoring. Although automated methods for MS lesion segmentation have usually been performed on individual MRI scans, tracking lesion activity for quantifying and monitoring MS disease progression, especially detecting new lesions, has become an important biomarker in recent years. This Ph.D. thesis aims to develop novel and fully automated DL approaches for detecting and segmenting MS lesions from a single time-point brain MRI of a patient and also new MS lesions between two time points brain MRI of a patient. DL techniques simplify the feature extraction process from the given input data. Therefore, in this thesis, DL approaches were investigated and examined, then exploited to improve the segmentation and detection of MS lesions for both challenging tasks. Accordingly, a novel dense residual U-Net model that combines Attention Gate (AG), Efficient Channel Attention (ECA), and Atrous Spatial Pyramid Pooling (ASPP) is proposed to enhance the performance of the automatic MS lesion segmentation using 3D MRI sequences. Similarly, a unique pipeline with a deep neural network that combines U-Net, attention gate, and residual learning is proposed to perform better MS new lesion segmentation using baseline and follow-up 3D FLAIR MR images for lesion activity determination. In the proposed novel dense residual U-Net model, convolution layers in each block of the U-Net architecture are replaced by residual blocks and connected densely. Then, AGs are exploited to capture salient features passed through the skip connections. The ECA module is appended at the end of each residual block and each downsampling block of U-Net. Later, the bottleneck of U-Net is replaced with the ASSP module to extract multi-scale contextual information. Furthermore, 3D MR images of FLAIR, T1-w, and T2-w are exploited jointly to perform better MS lesion segmentation. The proposed model is validated on the publicly available ISBI2015 and MSSEG2016 challenge datasets. This model produced an ISBI score of 92.75, a mean Dice score of 66.88%, a mean Positive Predictive Value (PPV) of 86.50%, and a mean Lesion-Wise True Positive Rate (LTPR) of 60.64% on the ISBI2015 testing set. Also, it achieved a mean Dice score of 67.27%, a mean PPV of 65.19%, and a mean sensitivity of 74.40% on the MSSEG2016 testing set. The results show that the proposed model performs better than the results of some experts and some of the other state-of-the-art methods realized related to this particular subject. Specifically, the best Dice score and the best LTPR are obtained on the ISBI2015 testing set by using the proposed model to segment MS lesions. On the other hand, the generated model for the lesion activity determination within the proposed pipeline has a similar architecture to U-Net and is formed from residual units which facilitate the training of deep networks. Networks with fewer parameters are designed with better performance through the skip connections of U-Net and residual units, which facilitate information propagation without degradation. AGs also learn to focus on salient features of the target structures of various sizes and shapes. The MSSEG-2 challenge dataset was used for training and testing the proposed pipeline, and the results were compared with those of other proposed pipelines of the challenge and experts who participated in the same challenge. According to the results obtained from the testing set, the lesion-wise F1 and Dice scores were obtained as a mean of 48 and 44.30%. For the no-lesion cases, the number of tested and volume of tested lesions were obtained as a mean of 0.148 and 1.488, respectively. The proposed pipeline outperformed 22 proposed pipelines and ranked 8th in the challenge for the Dice and F1 scores. It was also ranked 4th and 5th for the number of tested and volume of tested lesions, respectively.
-
ÖgeDenetimsiz derin öğrenme kullanılarak dijital meme tomosentezi görüntülerinde bulanıklığın giderilmesi(Lisansüstü Eğitim Enstitüsü, 2023-09-25) Aydın, Müberra ; Yıldırım, İsa ; 504201409 ; Biyomedikal MühendisliğiHer yıl binlerce kişinin ölümüne neden olan kanserin teşhisinde, tümörün doğru lokalizasyonu tedavi süreci için hayati önem taşımaktadır. Hastalığın erken teşhisi, kanserli dokunun büyümesini ve daha fazla dokuya yayılmasını önlemek için çok önemlidir. Tıbbi görüntüleme teknikleri, kanserin erken teşhisine önemli katkı sağlamaktadır. Kadınlarda kansere bağlı ölüm oranlarında en yüksek paya sahip olan meme kanserinin erken teşhisinde de görüntüleme teknolojilerinden yararlanılmaktadır. Özellikle 40 yaş üstü kadınların kendilerini kontrol etmeleri ve ailelerindeki kanser öyküsüne bağlı olarak düzenli taramalardan geçmeleri önerilmektedir. Bu tarama işlemlerinde yaygın olarak mamografi kullanılmakla birlikte, dijital meme tomosentezi (DBT) kullanımı da giderek yaygınlaşmaktadır. Mamografi iki boyutlu (2B) görüntüler oluştururken, DBT üç boyutlu (3B) görüntüler oluşturur. DBT, mamografide üst üste binme nedeniyle gizli kalmış lezyonların teşhisini mümkün kılmaktadır. Ayrıca taramanın farklı açılarda yapılması, oluşturulan görüntülerle yanlış pozitif oranlarını azaltılmasını sağlamaktadır. Taramaların sınırlı açılarla gerçekleştirilmesi, önlenemeyen hasta hareketleri ve dedektör odaklama aşamasındaki aksaklıklar DBT görüntülerinde bulanıklık artefaktlarına neden olabilmektedir. Bulanıklık etkisi, görüntü kalitesini gözle görülür şekilde düşürerek uzmanın görüntüdeki anormallikleri fark etme olasılığının da düşmesine sebep olmaktadır. Bahsi geçen dezavantajların azaltılması için, farklı modalitelerde çeşitli görüntü restorasyon teknikleri uygulanmaktadır. Bu çalışmada, DBT görüntülerinde tanısal doğruluğu azaltan bulanıklık etkisinin önüne geçebilmek için bir derin öğrenme modeli önerilmektedir. Temel gerçek görüntülere erişimin mevcut olmaması veya zor bulunması nedeniyle, model denetimsiz olarak tasarlanmıştır. Önerilen modelin eğitimi için kanser görüntüleme arşivinden alınan ve 5060 hastaya ait normal, işlem yapılabilir, biyopsi ile kanıtlanmış iyi huylu ve biyopsi ile kanıtlanmış kanser olarak etiketlenmiş görüntüleri içeren Meme Kanseri Taraması-Dijital Meme Tomosentezi (BSC-DBT) veri seti kullanılmaktadır. İşlemci kapasitesinin az olması ve dicom görüntülerin saklanması için çok fazla bellek gerekmesinden ötürü görüntüler png uzantılı olarak kaydedilmektedir. Biçimleri değiştirilen görüntüler ilk olarak kontrast uyarlamalı adaptif histogram eşitleme (CLAHE) ve yeniden boyutlandırma işlemlerini içeren bir ön işleme sürecine tabi tutulmaktadır. Veri setinden seçilen 2600 görüntü eğitim verisi, 350 görüntü validasyon verisi ve 260 görüntü ise test verisi olarak ayrılmıştır. Seçilen verilere farklı seviyelerde kernel boyutları ve sigma değerleri ile Gaussian bulanıklık filtreleri uygulanmıştır. AE (Autoencoder) ve GANs (Generative Adversarial Networks) modellerinin art arda kullanılması ile tasarlanan bu model 2B konvolüsyon, batch normalizasyon, LeakyReLU aktivasyonu, MaxPool ve Dropout katmanlarını içermektedir. Tasarlanan model, bulanık görüntüyü temel alarak orijinal görüntüyü yeniden oluşturmayı amaçlar. Bulanık görüntü, gerçek dünya uygulamalarında yaygın olarak bulunan düşük kaliteli veya bozulmuş görüntülerin modellenmesi amacıyla kullanılmaktadır. Önerilen modelin başarısı kontrast-gürültü oranı (CNR), ortalama mutlak hata (MAE) ve yapısal benzerlik indeksi (SSIM) ve uzman radyolog tarafından yapılan yorumlar ile değerlendirilmiştir. Nicel değerlendirmeler sonucunda bulanıklıktan arındırılan görüntülerin, bulanık görüntülere kıyasla orijinal görüntülere daha benzer olduğunu ortaya koymaktadır. Hem nicel sonuçlar hem de nitel değerlendirmeler, önerilen modelin DBT görüntülerindeki bulanıklaştırma artefaktlarını ele almada oldukça umut verici olduğunu ve bunun da teşhis doğruluğunu artırmasının beklenebileceğini göstermektedir.
-
ÖgeDesign and synthesis of fluorescent molecules for the detection of biologically and environmentally important species(Graduate School, 2023-03-10) Suna, Garen ; Öztürk, Turan ; Gündüz, Simay ; 509172017 ; ChemistryChemosensors are widely used for the detection of biologically and environmentally important substances. Especially cyanide, hydrazine, hypochlorite and gold ions are very important due to their high toxicity and wide usage area in the industry and daily life. Ingestion of toxic cyanide by humans in a certain amount can cause nausea, vomiting, unconsciousness, shock and even death. Similarly, taking hydrazine can have toxic and severe health effects that can cause allergies, nausea, vertigo, temporary blindness, acute poisoning, burns by skin contact or inhalation, and even cancer. When hypochlorite is taken in high amounts, it causes various diseases such as cardiovascular diseases, acute lung injuries, neurodegenerative disorders, Alzheimer, Parkinson, and cancer. Although gold ions have positive effects on the body in low amounts, they can cause some health problems through interactions with proteins, DNA and biomolecules when taken in high levels. Conventional techniques such as electrochemical analysis, chromatography, capillary electrophoresis, potentiometry and ion chromatography, which are instrumental devices used to detect these substances, are time-consuming and require expensive devices and complex operations. On the other hand, fluorescent probes have attracted significant attention due to their excellent sensitivity and selectivity, fast response, inexpensive instrumentation, easy operation, real-time imaging, and possible detection with the naked eye. The triphenylamine, thienothiophene and barbituric acid-based probe TTB enables discriminative detection of cyanide, hydrazine, and hypochlorite in different emission wavelengths. Rhodamine and triphenylamine-based probe RH-TPA enables multi-channel (colourimetric, fluorometric and electrochemical) detection of gold ions and BODIPY, and malononitrile-based probe BOD-CN enables fast, selective and sensitive detection of hypochlorite ions. In this thesis, the preparation of specific probes for fluorescence detection of cyanide, hydrazine, hypochlorite and gold ions were carried out. At the same time, practical applications of the probe molecules have been performed in various water samples, fruit, vegetable and dairy products.
-
ÖgeDesign of seafarer-centric safety system; mental workload (MWL) prediction(Graduate School, 2022-01-06) Özsever, Barış ; Tavacıoğlu, Leyla ; 512152011 ; Deniz Ulaştırma MühendisliğiIt is known that the human factor has a major effect on maritime casualties that cause great harm to the environment, economy, and maritime sector. It was stated that while human error is the primary contributor to accidents, a good part of collisions and groundings were related to the mental workload (MWL) of watchkeeping officers. Automation, mechanization, and the introduction of new technologies have changed the working conditions together with reducing the number of crew and increasing the MWL of operators. This indicates that human element-related issues will continue to be one of the major issues in marine transportation assets. In maritime-related studies, it has been analyzed mostly how the ship's environment, working period, and other factors affect the seafarers. Almost all maritime-related studies couldn't have the potential to develop an MWL prediction system for maritime operations aspect. However, lots of studies on drivers and pilots, have produced successful results for MWL prediction. Taking into consideration the fact that MWL has a major contribution to maritime casualties, the development of a real-time MWL prediction system is vitally essential for ships. By implementing the similar measurement techniques used in the studies on drivers and pilots, to maritime transportation, this study aims to classify the physiological responses of the operators that can produce an output for the state of the officer on duty as "Safe" or "Risky" from the collected physiological data and task load data during the seaborn operations. This study predicates the theories which are the statement "minimum performance requires sufficient behavioral activity" of Sheridan and Simpson (1979) together with the inverted U function of Yerkes and Dodson (1908) which presents the relationship between arousal and performance. Moreover, the theory of Young et al. (2015) which presents the relationship among mental workload, performance, task demand, and resource supply and indicates the overload region, guides this study in terms of building the structure of the experimental research. By being predicated on the above-mentioned theories, this study aimed to design a Cognitive Seafarer-Ship Interface (CSSI) which is a main part of the Seafarer-Centric Safety System. The physiological data of the 17 junior deck officers (12 subjects performed navigation scenario, 5 subjects performed cargo operation scenario) was recorded according to the design. By being correlated with the performance of the officer, the change of physiological responses of the subjects were analyzed in low and high task load levels. The medical decision-making process, which deduced "Safe" or "Risky", was run for this change. For performance measurement which is a part of a triangulated measurement strategy (Wierwille and Eggemeier, 1993), Officer Performance Model which is used for MWL classification, was developed for navigation and cargo operation tasks. Additionally, the inputs of the Task Load Estimator were defined as data transcription from navigational aids according to the results of classification. In summary, the following process was done and results were found.
-
ÖgeDevelopment of novel BCL-2 inhibitors for glial tumors by using in vitro and in vivo systems(Graduate School, 2022-05-31) Çalış, Şeyma ; Turanlı Tahir, Eda ; Avşar, Timuçin ; 521162117 ; Molecular Biology – Genetics and BiotechnologyGlioblastoma Multiforme (GBM) is the most malign form of glial tumors, which accounts for the majority of brain tumor cases worldwide. There have been different approaches to treat GBM effectively, and with the advancements made for the last decade molecular pathology, target driven therapy, and personalized medicine gained attraction. One of such promising targets for GBM is Bcl-2 induced intrinsic apoptosis pathway. Anti-apoptotic members of Bcl-2 induced intrinsic apoptosis pathway have an important role in the regulation of GBM cell death. In this thesis study, we screened seven potential Bcl-2 inhibitor compounds and evaluated their effects on proliferation of GBM cells as well as their inhibitory capacity of Bcl-2 protein. Of those, I further analyzed three of them namely 58, 243, and ind-199. 58 and ind-199 compounds did not show any significant anti-proliferation effect on GBM cells. Eventually, we decided to elucidate the mechanism of action of 243 compound, a thiazolidine derivative BH3 mimetic, which was the most promising one according to the in vitro proliferation experiments. I performed colony formation assay to assess proliferation of YKG1 GBM cells, additionally to the proliferation assay with A172 GBM cells. While 243 inihibited cell growth significantly compared to control group, Bcl-2 inhibitor ABT-199 did not inhibit cell proliferation. Moreover, I tested 243 on YKG1 tumorspheres to determine its effectivity on tumor initiating cancer stem cells (CSC). Both ABT-199 and 243 had inhibitory effect on CSC proliferation, however 243 was significantly more effective than ABT-199 when compared to control group. Since 243 is a Bcl-2 inhibitor, I analyzed key players of Bcl-2 family and intrinsic apoptosis pathway. I have analyzed gene expression levels of BCL2, BCLXL, BAX, CASP3, CASP7, and CASP9. Furthermore, I also analyzed genes related with cell death which are CASP8 and TP53. Time dependent quantitative RT-PCR results suggested that, GBM cells that are treated with Bcl-2 inhibitors ABT-263 and 243 acts differently in case of gene expressions related to apoptosis. Next, we wanted to show apoptotic cell death with Annexin V-PI assay. Interestingly, we did not detect significantly elevated apoptosis in A172 cells when they are treated with either ABT-199 or 243. Similarly, cell cycle analysis showed that 243 did not have any effect on cell cycle, altough ABT-199 induced G1 phase arrest. Moreover, I determined expression levels of apoptosis related proteins PARP, Caspase-3, and Caspase-9. I used staurosporine treatment as a positive control to induce apoptosis. None of the treatment groups apart from staurosporine increased cleaved-PARP expression. Similarly, I checked if there is a difference in expression of Pro-caspase-3 and Pro-caspase-9, and observed that only stauroporine treated group expressed lower levels of Pro-caspases, indicating that cleaved forms of both Caspase-3 and 9 were produced upon staurosporine treatment only. At this point, we hypothesized that both ABT-199 and 243 could only induce limited apoptotic cell death because BCL2 expression was relatively low in A172 cell line. Expectedly, when I compared gene expression levels among different cell lines, I observed that BCL2 expression was very low in A172 cells, and it was abundant in SH-SY5Y neuroblastoma cells. Therefore, I decided to analyze apoptosis of SH-SY5Y cells after a treatment with ABT-199 and 243. Within only 48 hours of treatment with both inhibitors, I observed apoptotic cell death of SH-SY5Y cells. Hence, we had a new hypothesis that when BCL2 expression is low, upon Bcl-2 inhibitor treatment, cells may die through autophagy since Bcl-2 forms a complex with autophagy related protein Beclin 1. I showed that 243 treatment significantly upregulated autophagy related genes such as BECN1, ATG5, and MAP1LC3B, whereas ABT-199 induced autophagy on limited level. Moreover, autophagy indicative LC3B-II expression was significantly upregulated on a protein level with the 243 treatment, when compared to control as well as ABT-199 treatment. Additionally, I determined protein expression level of p53, which has a role in the interplay between apoptosis, cell cycle, and autophagy. I observed that p53 protein expression was increased upon both ABT-199 and 243 treatment, when compared to control group. Expectedly, when we performed in silico computational analysis, Beclin 1:Bcl-2 interaction and binding of 243 to their BH3 binding domains, we observed that 243 binds to Bcl-2 through important interactions. Since 243 and Beclin 1 binds to Bcl-2 from the same domain, when cells are treated with 243, Beclin 1 cannot bind to Bcl-2 and therefore it is released to initiate autophagy. In addition, we demonstrated that 243 significantly reduced in vivo tumor growth and prolonged survival in orthotropic brain tumor models, compared to vehicle group as well as ABT-263 treated animals. Furthermore, I assessed the anti-proliferative effects of 243 on primary glial cell lines as well. 243 exerted anti-proliferative effect on all patient derived glioma cell lines that have different grades and histopathology, except OLG3 cell line which is a grade 2 oligodendroglioma. According to quantitative RT- PCR results of OLG3, OLG7, and GBM9 cell lines I observed that OLG3 has a lower expression level of BCL2. These results suggest that patients with high BCL2 expression might benefit from 243 treatment. Taken together, our results indicate that 243 disrupts Beclin 1:Bcl-2 complex, hence activates autophagic cell death, and may serve as a potential therapeutic for the treatment of GBM.
-
ÖgeDirectional wide band printed monopole antenna for use in microwave breast cancer imaging(Institute of Informatics, 2012-06-07) Golezani, Javad Jangi ; Akduman, Ibrahim ; 705101004 ; Satellite Communication & Remote SensingBreast cancer is the most common cancer in women. Detection of small breast lesions by mammography screening facilitates the cancer treatment by noninvasive techniques. Recently, new therapies than traditional surgery have been explored to satisfy these demands. The physical basis for breast cancer detection with microwave imaging is the difference in dielectric properties of normal and malignant breast tissues. Microwave imaging involves illuminating the breast with an ultra-wideband pulse from a number of antenna locations, then synthetically focusing reflections from the breast. The detection of malignant tumors is achieved by the coherent addition of returns from these strongly scattering objects.Radar-based microwave imaging techniques have been proposed for early stage breast cancer detection. Radar-based microwave breast imaging approaches involve illuminating the breast with an ultra-wideband pulse of microwaves and detecting reflections. The reflections are then processed to create images that indicate the presence and location of tumors in the breast. A key component of these systems is the antenna that is used to radiate and receive the ultra-wideband pulses. So the antenna design requirements for use in near field near surface measurement applications, such as radar-based microwave breast cancer imaging are as follows: radiation of ultra-wideband signal to transmit short pulses, size of the antenna on the order of a few centimeters to selectively illuminate and permit scanning, an optimum half power near-field beam width( HPBW) to avoid smearing of the scatterers that occurs if the field of view of each antenna is too broad, and finally a good impedance matching across the entire band, This ensures that most of the energy is transmitted. In order to decrease the HPBW of an antenna we have to increase the directivity of the antenna in a desired direction. Nevertheless, most of the wide band and UWB antennas like planar monopoles, which are in use, have almost Omni-Directional radiation pattern.Directivity can be achieved if the antenna is large in a desired direction, such as Horn or Vivaldi antennas. Printed disc monopole antennas with an L-shaped or parabolic-shaped ground plane are introduced as another type of directional antennas. In these antennas it has been shown how partial ground optimization influences the antenna?s performance, in maximizing the directivity and gain of the antenna. These kinds of directional antennas are similar to the UWB type Omni-Directional monopole antennas, where it is shown the effect of ground plane on obtaining the desired directional characteristics of the antenna.This Thesis presents a new design of directional wide band monopole antenna with parabolic-shaped ground plane. Ground plane of the antenna consists of a symmetrical parabolic curve, which its axis extended along the direction of the substrate?s diagonal. In order to accomplish high gain and directivity, axis of parabola in the ground plane is extended throughout the direction of square substrate?s diagonal that maximizes the capability of symmetrical ground plane as a reflector. The directivity of the antenna is further improved by inserting parabolic-shaped slots at the corners of ground plane. The second edge of the ground plane which is created by inserting the slots, behaves as an additional reflector which cause to increase in the gain and directivity.Then, the presented planar antenna is composed of a disc-monopole fed by a 50? microstrip line printed on a FR4 substrate. Simulation and measurements show that the proposed antenna has stable directional radiation pattern and higher gain compared to the previous directional monopole antennas. Impedance bandwidth of the antenna covers the frequency range of 4-9 GHz. Measured HPBW is among the degrees 54-22 in the same range of frequencies. In comparison with conventional antennas with a similar structure, gain of the antenna is improved between 1.1 and 3.1 dBi among 4-9 GHz. HPBW of the antenna is also between 5 and 15 degrees through the bandwidth .Results confirm the good characteristics for use in radar and microwave Breast cancer imaging applications where high resolution is required. For example, at 8.5 GHz, measured HPBW of the antenna is decreased from 38 degrees to 23 degrees (mentioned in the result section), which confirms a 40 % decrease in HPBW of the antenna (simulated HPBW is 26 = 33 % improvement). That is very important in order to increase the resolution of a radar system.As an additional attempt, another novel compact directional monopole antenna in microstrip technology is also presented. Dimensions of this antenna are considerably miniaturized in comparison with conventional directional antennas. The main effort is to convert an Omni-directional radiation pattern of a compact monopole antenna to the desired directional radiation pattern, by using a novel ground plane, and a parasitic element. The ground plane and parasitic element are accurately designed in a way that make the surface currents of radiating elements to move toward the desired direction, which increase the radiation density in the preferred direction and also decrease the radiation intensity in the opposite sides. Simulations confirm a good directional characteristic of the antenna at the frequencies between 5 and 9 GHz. Gain of the antenna is increased over 5 dBi at the desired frequencies. Reflection coefficient bandwidth of the antenna covers the frequencies among 5-9 GHz. Miniaturized size and an acceptable directional characteristic of the antenna make it possible to use it in the microwave imaging systems and radar applications.
-
ÖgeEgzotizm ve kültürlerarasılık kavramları ekseninde Shakulute(Lisansüstü Eğitim Enstitüsü, 2022) Ergen Kay , Elif ; İncedere, Zeynep Gonca ; 760990 ; Çalgı-Ses Bilim DalıBu çalışma hibrit shakulute çalgısının egzotizm ve kültürlerarasılık kavramlarıyla tartışılmasına odaklanmaktadır. Bir kültür ürününün tercih ya da kabul edilirliği yolunda etkisi altında kaldığı kavramların tartışması üzerinden yürütülecek olan bu tez, söz konusu kavramları dört başlık altında toplamıştır. Kavramlar özelden genele doğru sıralandığında; başlangıç noktası, konunun öznesi olan melez çalgı "shakulute" den dolayı 'melezlik' olarak belirlenmiştir. Konunun devamında sırasıyla melezliğin sonuçlarından biri olan egzotiklik, yine aşkın kültürleşmenin getirisi olan kültürlerarasılık ve son olarak bakir olarak görülen kültür ürünlerinin herhangi bir seçilim skalasına dahil olup küresel sayılmasının detaylarının anlaşılması için küresellik tanımı tartışılacaktır. Kavram tartışmaları sonrasında shakuhachi ve shakuhachinin modernizasyon sürecinin başlangıcından itibaren nitelik ve niceliksel olarak geçirdiği değişimleri ve bu değişimlerin ürünleri olan okraulo ve shakulute tanıtılıp, edinilen kavramsal bilgiler doğrultusunda yorumlanacaktır. Tez sunum aşamasında shakuhachinin kültürlerarasılık etkisi altında oluşan hibrit hali olan shakulute çalgısı için bestelenmiş eserlerden örnekler icra edilecektir.