Recently Added Theses
View AllCentriolar satellites are required for efficient ciliogenesis and ciliary content regulation.
Centrosome is the main microtubule organizing center of the cell. It has the role in cell division, cell shape and migration. Other than these roles, centrosome has an important function which is forming primary cilium. Primary cilium is a microtubule-based organelle serving as signaling hub for the cell. Structural or functional defects associated with centrosome/cilium complex lead to genetic diseases called ciliopathies. In order to understand molecular mechanism under ciliopathies, it is important to understand how centrosome/cilium complex is regulated in time and space. Centriolar satellites are the third component of the centrosome/cilium complex In the second chapter of my thesis, I characterized the cells without centriolar satellites in terms of ciliogenesis and ciliary function. I established the satellite-less cells by knocking-out PCM1 gene in inner medullary collecting duct (IMCD3) cells. PCM1 is the scaffolding protein of the centriolar satellites. Satellite-less IMCD3 cells do not ciliate efficiently as much as control cells. Content and function of cilia formed by satellite-less cells are also different. To understand how cellular process are affected in PCM1 knock-out cells, I applied tandem mass tag (TMT) labeling‐based quantitative analysis to compare the global proteome control and satellite-less cells. This analysis revealed that many processes such as actin cytoskeleton, cell migration and adhesion, endocytosis, neuronal processes are affected in the absence of PCM1 protein. With these observations, I showed that centriolar satellites are important to regulate ciliogenesis, ciliary content and function. However, the mechanism behind this regulation is poorly understood. In the third chapter of my thesis, I applied the miniTurbo labeling method to compare interaction partners of PCM1 in asynchronous and ciliated cells. The aim of this chapter to find interaction partners of PCM1 specific to ciliated cells to explain mechanism of regulation by centriolar satellites during ciliogenesis. After miniTurbo experiments and mass spectrometry analysis, we determined a set of protein which interact with PCM1 in ciliated cells. Among these proteins, we checked the localization and function of the TBC1D31 protein by loss of function experiments. In this chapter, we determined the set of protein might have a role in regulation of ciliogenesis with centriolar satellites. The interactions between these proteins with PCM1 and their relationship in the regulation of ciliogenesis are going to be explored in our future studies.
Aydınlatılmış onam ve insan hakları
Ötanazi, intihara yardım, tedavinin reddi gibi birçok tartışmalı konu tıp etiği ve hukukun işbirliğini gerektirmektedir. Tıbbi müdahalelerin ilgililerin hür iradesine dayanması gerekliliği de yine hukuk sistemlerince güvence altına alınmalıdır. Bu bağlamda, karşımıza çıkan kavram aydınlatılmış onam olacaktır. Hastaların kendilerine uygulanacak tıbbi müdahaleler hakkında yeterince bilgilendirildikten sonra ilgili müdahaleyi kabul ya da reddetmeleri anlamına gelen aydınlatılmış onam insan onuru ve özerkliğinin bir gereğidir. Aydınlatılmış onamın; insan onuru ve kendi kaderini belirleme hakkı, yaşama hakkı, sağlık hakkı gibi en önemli insan hakları ile yakın ilişkisi sebebiyle başlı başına bir insan hakkı olduğu ileri sürülebilir. Bu kabul aydınlatılmış onamdan beklenen faydaların gerçekleşebilmesi ve hasta özerkliği ve kendi geleceğini belirleme hakkının kâğıt üzerinde soyut bir kavram olarak kalmaması açısından önemlidir. Bu sebeple çalışma, aydınlatılmış onam hakkının etkinliği ve etkililiği bakımından tespit ve fikirler sunmayı amaçlamaktadır. Bu doğrultuda çalışma aydınlatılmış onamı; etik ve ahlak boyutu, neliği ve aydınlatılmış onam hukuku olmak üzere üç ayrı başlık altında irdelemektedir. Birinci bölüm aydınlatılmış onamın bir insan hakkı olarak kabulüne gerekli altyapıyı hazırlarken, ikinci bölüm çalışmanın teknik yönünü oluşturmaktadır. Üçüncü ve son bölüm ise uluslararası ve ulusal hukukta aydınlatılmış onamın konumuna ve bu konumun geliştirilmesi için yapılması gerekenlere işaret ettiği için önemlidir. Anahtar Kelimeler: aydınlatılmış onam, hasta özerkliği, kendi geleceğini belirleme hakkı, tıp etiği, insan hakları
Deep learning approaches for vocal tract boundary segmentation in rtMRI
Recent advances in real-time Magnetic Resonance Imaging (rtMRI) provide an invaluable tool to study speech articulation. Development of automatic algorithms to detect the landmarks defining the boundaries of the vocal tract (VT) is crucial for a wide range of research, from speech modeling and synthesis to clinical research. In this thesis, we present two effective deep learning approaches for supervised detection and tracking of vocal tract contours in a sequence of rtMRI frames: (1) we propose a fully convolutional network to estimate the VT contour in heatmap regression fashion and (2) we introduce a deep temporal regression network which learns the non-linear mapping from a temporal overlapping fixed-length sequence of rtMRI frames to the corresponding articulatory movements. We as well introduce two post-processing algorithms succeeding the deep models, to further improve the quality of VT contour detection: (i) a novel appearance model based contour refinement to overcome the potential failures of data-driven approaches for highly deformable articulators and (ii) a spatiotemporal stabilization scheme to stabilize the estimated contours in space and time by removing the spatial outliers and temporal jitter. The proposed VT contour tracking models are trained and evaluated over the large audiovisual USC-TIMIT dataset. Performance evaluation is carried out using various objective assessment metrics for the spatial error and temporal stability of the contour landmarks in comparison with several baseline approaches from the recent literature. Results indicate significant improvements with the proposed methods over the state-of-the-art baselines. In addition, we develop a graphical user interface (GUI) for the analysis of the rtMRI data, integrated with various attributes including automatic segmentation of the VT boundaries using the proposed contour estimation methods and calculation of tract variables and cross-sectional distance.
Full-color holographic near-eye displays
Near-eye displays (NEDs) for augmented reality (AR) applications are expected to be the next computing paradigm. NEDs offer to combine computer-generated visuals with our physical world in a seamless fashion. Depth cues and natural blurring of images are all critical for a comfortable 3D experience with near-eye displays. Holography for NEDs is a commonly accepted strong candidate in meeting the human visual system's demands by offering natural depth cues. Holographic near-eye displays (HNEDs) deliver virtual images using computer-generated holograms (CGHs) displayed on spatial light modulators (SLMs). Holographic displays allow for a vast range of optical architectures that are not possible with conventional microdisplay-based designs. However, due to the current technological limitations of SLMs, most existing HNEDs have a limited field of view (FOV) and viewing region around the eye pupil (i.e., eyebox size). However, improving SLMs have a positive impact on improving FOV and eyebox size in HNED design. In this thesis, we propose various solutions for overcoming the current technological limitations of SLMs and HNEDs. We start by offering a paraxial matrix optics-based analysis of a conventional HNED design to formulate the relation between eyebox, FOV, and SLM characteristics. We developed a CGH computation procedure that applies to arbitrary paraxial optical architectures, where the SLM illumination beam can be collimated, converging, or diverging. The virtual or real SLM image as seen by the eyebox plane may form at an arbitrary location. Using this approach, we designed full-color HNEDs with varying FOV and resolution characteristics and proper depth control. We demonstrated a lensless HNED architecture with diverging beam illumination, which provides 3D images within a wide FOV (70°) at retinal resolution (30 cycles-per-degree), exceeding 4,000 resolvable pixels on a line. The experiments using binary holograms imprinted on masks prove that the proposed CGH computation procedure eliminates chromatic aberrations and speckle noise observed in all other laser-based displays. We also designed two systems with 10° and 20° FOV using dynamic SLM. While the first design has a uniform resolution, the second design demonstrates a foveated display, which has gradually degrading resolution across the FOV. To further explore HNED architectures, we analyzed the light source coherence requirements and investigated HNED designs utilizing light-emitting diodes (LEDs). While laser light sources have the highest degree of spatial and temporal coherence, lasers' usage in direct contact with a human may cause health hazards. We show that under certain design restrictions, it is possible to utilize LEDs instead of lasers and get better quality holographic images. We analyzed the effect of LED emission areas on image resolution, quality, and depth perception. Lastly, we designed micro-mirror array (MMA) based thin components and demonstrated that those could be used as off-axis thin lenses in AR displays to reduce size and volume.
mmWave channel model for intra-vehicular wireless sensor networks
Intra-vehicular wireless sensor networks (IVWSNs) have significant potential to reduce part, manufacturing and repair costs, facilitate the integration of new nodes and provide more freedom for the sensor placement in previously impossible locations by obviating the need for wiring harness. mmWave stands up as a promising candidate to fulfill the high reliability, security and low latency requirements of IVWSNs, exploiting the availability of large bandwidth at high frequencies and high nominal gains with directional antennas. This work focuses on building the channel model for the engine compartment, passenger compartment and beneath the chassis of a vehicle by conducting vast number of measurements for 14x14, 13x13and 15x15 transmitter and receiver links in a Fiat Linea, respectively. The path loss exponent is approximately 3, showing almost no variation within different compartments. The power variation around the path loss model has a Generalized Extreme Value (GEV) distribution with zero mean for all compartments and 5 dB standard deviation for the engine compartment and approximately 7.6 dB standard deviation for the other two compartments. A modified Saleh - Valenzuela (SV) model is used to represent the clustering of power delay profiles (PDPs). Log-normal distribution is used to model the inter-arrival times of clusters, while the dependencies of cluster amplitude and ray decay rate on the cluster arrival times are represented by a dual slope linear fit model with breakpoints 1.2 ns and 5.6 ns for engine compartment, respectively, and 1.6 ns and 2.6 ns for the other two compartments, respectively. The experimental PDPs vary around the SV model and these variations are represented by a normal distribution with zero mean and 5.8 dB standard deviation, which is independent of both the delay bins and the compartment of the vehicle. All these findings are used to build a simulation model for each compartment of the vehicle. The simulation model is validated by comparing the distributions of the received powers and Root Mean Square (RMS) delay spreads of the experimental and simulated PDPs.
Molecular epidemiology of carbapenem resistant klebsiella pneumoniae in bloodstream infections
Carbapenem resistant Klebsiella pneumoniae (CRKP) has become a clinically important pathogen causing worldwide nosocomial infections that are associated with high rates of mortality. High risk clones of CRKP carrying KPC, NDM and OXA-48-like carbapenemases have spread worldwide. Resistance to carbapenem has limited the effective and safe treatment options, thus causing increased patient fatality. In this study, our aim was to describe molecular epidemiology of CRKP bacteremia in Turkey and to evaluate the effect of carbapenemase producing high risk clones on mortality. A total of 254 CRKP bacteremia isolates from 13 tertiary care centers in Turkey were collected between June 2018 and June 2019. The 30-day mortality of the patients was recorded. Meropenem, colistin, and ceftazidime/avibactam minimum inhibitory concentrations were determined by meropenem Etest and broth microdilution methods. Carbapenemase genes (blaOXA-48-like, blaKPC-2, blaNDM-1) were detected by multiplex PCR. For genotyping of the isolates pulsed field gel electrophoresis and multilocus sequence typing were performed. All analyses were performed using STATA software version 16.0. The ST2096 constituted the largest clonal type with 62 isolates (30%) followed by ST101 with 36 isolates (18%) and ST14 with 27 isolates (13%) in the CRKP group. Fifty-one of 254 isolates were detected as meropenem susceptible and classified as carbapenem susceptible Klebsiella pneumoniae. The OXA-48-like carbapenemases comprised the largest carbapenemase group with 171 isolates (91%), NDM-1 was detected in 40 isolates (21%). OXA-48-like carbapenemases were mainly carried on ST2096 in 61 isolates and on ST101 in 35 isolates. The number of OXA-48-like and NDM-1 co-producer was 30 (16%) and 19 of them (63%) belonged to the ST14 clone. Overall colistin susceptibility was found as 38%. The ST101 and ST2096 clonal types had high colistin resistance rates with 83% and 81%, respectively. Overall ceftazidime-avibactam was the most active antibiotic with 84% susceptibility rate but the isolates belonging to ST14 had the lowest susceptibility rate (22%). The 30-day all-cause mortality was 40% for all patients. Mortality rates in infections with the ST2096, ST14 and ST101 clonal groups were 50%, 53%, and 41%, respectively. ST2096 (P=0.02) and ST14 (P=0.002) clonal types were found to be associated with high mortality. In conclusion, the emerging CRKP ST2096 clone possessing OXA-48-like is now the predominating clonal type in Turkish hospitals. Epidemiology of carbapenemases is shifting towards MBL and non-MBL co-producers. High colistin resistance and mortality rates in clones of CRKP ST14 and ST2096 indicates successful adaptation and severe disease production capacity of these clones. High ceftazidime/avibactam resistance in MBL producer ST14 clone demonstrates an urgent need for new antibiotics that are active not only against OXA-48-like producers but also against MBL producers.