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Archived Theses
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Archived Theses
A tool for verifying noninterference property for HDL
Hardware description languages started to adopt high-level functionalities. Through the flexibility of high-level programming, hardware designers can leverage object-oriented programming and functional programming paradigms to specify the hardware for quicker design time. This transition to high-level hardware descriptions created a new set of problems about verifying their noninterference property. By extending a high-level HDL, this thesis shows how to approach and solve this new set of problems and thus preventing information leakage. SecChisel (based on Chisel HDL) gives the ability to design circuits which have algorithmically verifiable noninterference property. SecChisel handles the creation of temporary variables and cascaded propagation of security tags to these new variables which are unique problems that only occurs when the host language creates an intermediate representation of the designed circuit. SecChisel algorithmically verifies a design by transforming and modeling the design in a satisfiability modulo theory (SMT) solver. By building and verifying hardware designs, we demonstrate that SecChisel provides a simple way to verify circuit design's noninterference property at compile time with no overhead.
Developing a new design passive house with a partial double-skin façade, double-skin roof, underground space and earth tube based on energy and airflow performance
This research originates from the interest in developing products with a holistic and interdisciplinary systems engineering approach, toward fostering sustainability. The study develops a new-design passive house with a double-skin envelope that delivers better energy consumption performance for heating and cooling relative to a conventional reference house, while achieving comfort-level indoor temperatures. A single-façade reference house is designed with the identical geometry, material and conditions of the new house living quarters, in order to demonstrate the performance of new house using a valid comparison. The new and reference houses are simulated cases and are not calibrated by actual models. The Soft Systems Methodology which enables designers to make better decisions at the earliest design stage is applied integrated with hard methods for the conceptual model development and performance comparison. Additionally, fluid dynamics behaviour of the air inside the double-skin envelope is analysed to demonstrate the airflow's contribution to the energy performance. The energy simulations demonstrate that the heating and cooling demands of new house are 19.1 per cent and 18.8 per cent lower than those of reference house, respectively. Furthermore, the computational fluid dynamics simulations reveal that turbulent airflow in the underground space on summer day increases heat transfer, and laminar airflow in the double-skin roof on winter night decreases such transfer.
A non-fiber optical set up for the measurement of patient response time in functional magnetic resonance imaging
Functional imaging is imaging which relates body function or mental activity to specific locations in the brain. It has become a powerful instrument to study local neuronal activity involved in motor, sensory and/or cognitive tasks. Extension of this technique to the spinal cord shows great promise for research and clinical applications. The current knowledge of neuroanatomy is mainly based upon invasive anatomical and pathological research. fMRI is a promising technique to demonstrate neuronal activity as it is performed in a noninvasive way. Thus the technique may have important clinical uses.The main advantages to fMRI as a technique to image brain activity related to a specific task or sensory process include 1) the signal does not require injections of radioactive isotopes, 2) the total scan time required can be very short, i.e., on the order of 1.5 to 2.0 min per run (depending on the paradigm).Although most fMRI examinations in routine practice employ simple patient response methods such as finger tapping, in modified fMRI examinations where the correspondence between performance and brain activation is studied, some additional instrumentation, like ?patient response switch (PRS), interface and recorder? is required. PRS based instrumentation makes patient reaction times to be measured. A Fiber Optic Button Response System (FO-PRS) mainly consists of fMRI Button Response unit (e.g., Psychology Software Tools, Pittsburgh, PA) with MR Projection System. The Fiber Optic Button Response System is an fMRI ready subject response collection system which has been engineered to gather subject responses and verify signals.The Fiber Optic Button Response Units attach to the subject's wrists and can be adjusted during scanning. These units are completely fiber optic and connect to a fiber Optic Interface Console located in the control room through an available wave guide. The interface console provides real-time feedback of subject responses via LED indicators and includes a set of switches which can be used to make responses for the subject as needed. The system provides TTL output signals that can be used to interface with other data collection devices and software. The interface console comes with a RF Pulse that the computer interprets as another button press, allowing the user to synchronize their experiments with the MR scanner.Such a commercially available standard unit comes with some (14-meter long) cables, and provides serial port and USB connection to the data collection computer. However, an additional waveguide is required between the patient room and the operating room. On the other hand, existing wave-guide channel may not be employed, since it may already be crowded with the earlier installed cables or the length of the supplied cables can be too short to provide the required connection. These difficulties prevent the practical use of such a technique, or require hiring of expensive skilled labor for extra cable installation, isolation and RF shielding.At present optical means of fMRI instrumentation is preferred, because, there exist intensive electromagnetic signals generated by gradient and RF coils (during an fMRI examination, in particular). In addition, there is a strong constant magnetic field (as high as 3 Tesla) within the patient room, and optical signal processing may seem to be reasonable to avoid distortions in such an environment.In this study, we show that relatively expensive fiber optical unit and fiber optical interface can be replaced by simple electronics without any disturbance to stimulus measuring unit as well as to the MRI. The cost of the measuring and interface unit whose performance has been reported in this work is very low as compared to commercially available equipment.
Plant suspension culture derived extracellular vesicles
Although extracellular vesicles (EVs) are an ever-present part of life, research of non-mammalian EVs have been severely limited compared to the studies of human EVs. Initial studies of plant EVs already report promising results, such as therapeutic effects for various types of cancers, colitis, immunomodulation, and wound healing. However, there are still many unknowns in plant EV research. A large majority of the articles published in the field fail in adhering to the standards and definitions set in international guidelines of EV research. The abundant contaminants created due to the harsh isolation procedures, lack of adequate controls, and incomplete characterization of the isolated EVs makes these findings questionable. The issues are exacerbated due to a lack of a plant EV isolation method or biomarkers agreed upon by the scientific community. This dissertation attempts to address this issue by providing a complete workflow for the isolation and characterization of true plant EVs using plant cell suspension cultures. Using this workflow, we have isolated and characterized EVs from Nicotiana tabacum, Vitis vinifera and Stevia rebaudiana cell cultures. Proteomic analysis of N. tabacum sEVs revealed the presence of eight proteins suggested as plant EV biomarker candidates. Furthermore, we ran an ortholog protein discovery analysis using proteomes of N. tabacum and seven other plant EV proteomes against top human EV proteins. We identified 116 human proteins with plant orthologues, with 24 of these proteins being present in more than five or more plants. Our findings prove that plant cell suspension cultures can be used for the production of highly pure plant EVs. Plant EVs have considerable potential as therapeutic agents or drug delivery devices, which can be easily, and efficiently produced in a large scale manner. Finally, the biomarkers identified in this study can pave the way for future studies in the field of plant EV research.
Determining the criteria for attaining flexibility to the multiple housing design
Multiple housings are a type of housing that is produced regardless of a specific dweller group and they must be designed with the flexibility to meet the needs of dwellers for change in order to appeal to a wide audience of dwellers who will use the housing. Flexibility is a design parameter that must be considered to ensure the adaptation between the house and the dweller and that the housing can be used for long when the needs for change in the housing arise. From this point on, this thesis aims to determine the criteria that may help to attain flexibility in multiple housings by focusing on the reasons that lead to the need for flexible housing. The chapters and contents of the thesis are as follows: In the first chapter, the intention of doing this study, the extent of the thesis and the methods followed throughout the study are compiled under the title of the thesis method. Existing studies, articles, theses, books are examined. In the second chapter, the flexibility concept is described, classified and the need for flexibility in housings is emphasized. Flexible housing examples from past to present have been examined. In the third chapter, the main reasons for the need for flexibility in housing design are mentioned. In the fourth chapter, flexibility in multi-house production is generally evaluated under the headings of strategies, collaborative planning, modular design. In the fifth chapter, it is aimed to set criteria for flexible multi-housing design in the consideration of the obtained data and the production of two existing multi-housing design is illustrated and evaluated under the criteria. In the sixth final chapter, the overall results of the set criteria to attain flexibility to multi-housing design is put forth.
Silymarin içeren nanopartikül formülasyonu geliştirme ve karaciğer koruyucu etkilerinin değerlendirilmesi
Last decades, many individuals have preferred some medicinal plants to treat the diseases they suffer from and to prevent various diseases. Therefore, recent scientific studies have focused on investigating the effects of plants on diseases. The Silybum marianum, used onwards first ages and whose effects on the liver are known, is one of them. In this study, the effects of Silybum marianum active substances silymarin, and their nanoparticles on the liver disease were observed. While the nanoparticles were prepared using soy lecithin, Silybum marianum extracts, which are active ingredients with the incorporation technique, were obtained from three different sources. In the light of previous studies, it has been seen that it is appropriate to mix soy lecithin and extracts in a 1:1 ratio. While soy lecithin is being prepared, the homogenizer and probe sonicator technique are applied, while Silybum marianum extracts are prepared by solvent extraction method. After incorporation, the probe sonication method was used to mix, decrease the particle size and be a homogenous mixture. Moreover, in order to increase the stability, the freeze-dried technique was used for soy lecithin, extracts, and the final formulations. The characterization of formulation size, zeta potential, and PDI was observed by using the DLS technique, the release profile of three different formulations, and prepared calibration curve were performed by using HPLC. In vivo studies, the procedures were performed on four different groups which were determined as the nanosilymarin formulation applied after the liver damage was induced, the other was treated with pure silymarin formulation under the same condition, the control group (healthy) and the last one who did not receive any treatment after induced liver damage. All groups have six Sprague Dawley, male and young rats. After that, histopathological and HPTLC tests were done. As a result of in vitro, in vivo animal experiments and histopathological studies, it has been observed that nanoparticle-containing standardized seeds are more effective.
Effectiveness of MEISi-2 treatment in prostate cancer cell lines
MEIS proteins are histrocally associated with tumorigenesis, metastasis and invasion in cancer. MEIS and associated PBX-HOX proteins may act as tumor suppressors or oncogenes in different cellular settings. Their expressions tend to be mis-regulated in various cancers. Bionformatical analyses suggest their upregulation in leukemia/lymphoma, thymoma, pancreas, glioma, and glioblastoma, and downregulation in cervical, uterine, rectum and colon cancers. However, every cancer type includes, at least, a subtype with high MEIS expression. In addition, studies highligh that MEIS proteins and associated factors may function as diagnostic or therapeutic biomarkers for various diseases. In this study, the function of MEIS1-2-3 proteins in prostate cancer (PCa) cell lines was investigated in vitro. In addition, MEIS inhibitors (MEISi-2), the first in its class, the MEIS homeodomain inhibitor has been shown to have a potent chemotherapeutic agent potential in PC-3, DU145, 22Rv-1 and LNCaP, prostate cancer cell lines. The effects on MEIS inhibitors in PCa cell lines are that reveal cytotoxicity and reduce cell viability. Also, intracellular ROS levels and MEIS protein expression were upregulated post MEISi-2 treatment. Also, MEISi-2 treatment resulted in slightly increase of Pca cell migration and the alteration of cell cycle of Pca cell lines. Overall, it is the first time that Pca cell lines necessitate basal MEIS1/2/3 expression for survical in vitro.
The effect of wheat (Triticum aestivum L.) derived exosomes on wound healing
Wound healing is the main physiological process which undergoes homeostasis, inflammation, proliferation, migration and tissue remodeling. Acute injuries usually heal in a short period of time but chronic illnesses associated with infection and prolonged inflammation, may resulted with the life-threatening infections, limb amputations that presents a serious challenge for the current technology. Although wound healing has been studied for decades, improved drugs are not still effective enough due to their high cost, low efficiency, having patient specific response, requiring wound care facilities and severe side effects. In this sense, developing new, safe, self-applicable, effective and cheap wound care products is still an attractive area of international research. Cell to cell communication is compulsory in order to sustain tissue homeostasis but most communication mechanisms between cells requires a coordination of the receptors and the signaling molecules. Recently, nano vesicle mediated cell communication become prominence because of the ability to shuttle different molecules from producing cells to the target cells via extracellular vesicles called exosomes. Previous studies reported that, exosomes released from plants such as grape, grapefruit, ginger and carrot have anti-inflammatory and anti-cancer properties. Although the underlying mechanisms of wound healing process of plant exosomes are still unknown. For this reason, in this study, for the first time, rate limiting factors of wound regeneration such as cell proliferation, migration, angiogenesis, gene and growth factor expression cell migration and proliferation was stimulated by using wheat derived exosomes by using both in vitro and in vivo approaches. According to the results, wheat exosomes increased cell proliferation, migration and angiogenesis, have anti-inflammatory effect, increased essential growth factor, and gene expression levels of HDF, HUVEC and HACAT cells in vitro. Moreover, wheat exosome-containing hydrogel formulations improved wound healing and histopathological rates in vivo. All in all, this research indicates a brand-new scope for wound healing therapeutics using wheat derived exosomes for the first time.
Solanesol production from Nicotiana tabacum cv. Xanthi cell suspension culture and process scale-up
Plants are important sources for wide range of different chemical compounds used in the production of fragrances, pigments, flavors, industrial feedstock, antimicrobials and pharmaceuticals. These chemicals are known as plant secondary metabolites which are generally responsible for the protection of the plant against environmental stress factors. Solanesol is a non-cyclic terpene found mainly in Solanaceae family plants and known to have highest accumulation in Nicotiana tabacum (tobacco) with 0.04-3.6 percent of leaf dry weight. It has antimicrobial, anti-cancer and anti-inflammatory effects that is mainly used as a precursor of Coenzyme Q-10. It is mainly extracted from the plants instead of chemical synthesis due to its long carbon chains. Secondary metabolites are generally extracted from whole plants which require large lands for growth, optimal environmental conditions and it is also labor intensive. Therefore, using plant cell suspension culture systems for the production of secondary metabolites has become one of the most important tools. In this study, it was aimed to achieve solanesol extraction from Nicotiana tabacum cv. Xanthi cell suspension culture and process scale-up of the suspension cultures. To our knowledge, this is the first study in the literature that focuses on the production of solanesol from tobacco cell suspension culture instead of whole tobacco plant or tobacco waste. N. tabacum cv. Xanthi callus cell lines were used to initiate the cell suspension culture which was maintained throughout the study. Optimal pH of the cell suspension cultures were determined as 6, cells were in log phase between days 1-11 and in stationary phase between days 11-15 according to the fresh weight, dry weight, pH and sugar consumption analysis. Optimal subculture period was determined as 7 to 9 days. Solanesol was extracted from N. tabacum cv. Xanthi cell suspension cultures for the first time in literature and had the average production of 14.56 ± 4.71 mg/ml which was the 1.46 percent of the dry weight. Scale-up parameters were optimized for growing plant cell suspension cultures in a stirred-tank bioreactor. This study will be the foundation for large-scale production of solanesol from N. tabacum cv. Xanthi cell suspension cultures.
Investigation of influence of drugs on cellular metabolism in 2Dc cell culture using surface-enhanced raman scattering
Raman spektroskopisi (RS), etiketsiz bir numuneden moleküler düzeyde bilgi sağlayan güçlü bir titreşim spektroskopik tekniktir. yüzeyde zenginliştirilmiş Raman saçılımı (SERS), Raman Spektroskopisinin oldukça hassas bir modudur ve yüzeydeki moleküler bileşimi veya çok yakın çevresindeki soy metal partiküllerin boyutu, saniyede iki büyüklükten daha az büyüklükte tanımlanmasına yardımcı olabilir. Metformin (MET), mitokondriyal solunum zinciri kompleksi I, hücre proliferasyonu, protein sentezi ve glukoneogenezi etkileyen bir ilaç molekülüdür. 6-Merkaptopürin (6-MP), antijen uyarımını takiben serideki nükleik asit metabolizması ve protein senteziyle ilgisi ve hücreler üzerindeki sitotoksik aktivitesi ile düzenlenebilen immünosüpresif özelliklere sahiptir. Bu çalışmada, SERS'in ilaçların hücre metabolizması üzerindeki etkisini izleyebilme potansiyeli, model ilaçlar olarak metformin ve 6-Merkaptopurin kullanılarak araştırılmıştır. Çalışma için iki hücre hattı, A549 ve Beas-2b seçildi. Ortalama boyutu 50 nm olan altın nanopartiküller, SERS substratları olarak seçildi. Metformin tedavisinde nükleik asitler, amino asitler ve fosfolipid zirveleri değişti. Bu değişikliğin nedeni, proliferasyonun inhibisyonunu ve protein sentezini ve lipid ve kolesterol biyosentezinin baskılanmasını sağlayan MET mekanizmalarıdır. Nükleik asitlere ve proteinlere karşılık gelen SERS pikleri, 6-Merkaptopürin tedavisi ile değiştirildi. Gözlemlenen spektral değişiklikler, de novo purin sentezinin ve protein sentezinin engellenmesine atfedilir. Hücrelerin artan konsantrasyonlarda ilaç moleküllerine maruz kalması üzerine gözlemlenen spektral modeldeki değişiklikler, bilinen ilaç metabolizması mekanizmalarıyla ilişkilendirilmeye çalışılır. Sonuçlar, MET ve 6-MP durumunda gösterildiği gibi, SERS'in ilaç moleküllerine maruz kalması üzerine hücresel düzeyde metabolik değişiklikleri izlemek için kullanılabileceğini göstermektedir.