Proposed are novel sensors for extreme environment power plants, laser beam analysis and biomedicine. A hybrid wireless-wired extreme environment temperature sensor using a thick single-crystal Silicon Carbide (SiC) chip embedded inside a sintered SiC probe design is investigated and experimentally demonstrated. The sensor probe employs the SiC chip as a Fabry-Perot (FP) interferometer to measure the change in refractive index and thickness of SiC with temperature. A novel temperature sensing method that combines wavelength-tuned signal processing for coarse measurements and classical FP etalon peak shift for fine measurements is proposed and demonstrated. This method gives direct unambiguous temperature measurements with a high temperature resolution over a wide temperature range. An alternative method using blackbody radiation from a SiC chip in a two-color pyrometer configuration for coarse temperature measurement and classical FP laser interferometry via the same chip for fine temperature measurement is also proposed and demonstrated. The sensor design is successfully deployed in an industrial test rig environment with gas temperatures exceeding 1200 C. This sensor is proposed as an alternate to all-electrical thermocouples that are susceptible to severe reliability and lifetime issues in such extreme environments. A few components non-contact thickness measurement system for optical quality semi-transparent samples such as Silicon (Si) and 6H SiC optical chips such as the one used in the design of this sensor is proposed and demonstrated. The proposed system is self-calibrating and ensures a true thickness measurement by taking into account material dispersion in the wavelength band of operation. For the first time, a 100% repeatable all-digital electronically-controlled pinhole laser beam profiling system using a Texas Instruments (TI) Digital Micro-mirror Device (DMD) commonly used in projectors is experimentally demonstrated using a unique liquid crystal image generation system with non-invasive qualities. Also proposed and demonstrated is the first motion-free electronically-controlled beam propagation analyzer system using a TI DMD and a variable focus liquid lens. The system can be used to find all the parameters of a laser beam including minimum waist size, minimum waist location and the beam propagation parameter M2. Given the all-digital nature of DMD-based profiling and all-analog motion-free nature of the Electronically Controlled Variable Focus Lens (ECVFL) beam focus control, the proposed analyzer versus prior-art promises better repeatability, speed and reliability. For the first time, Three Dimensional (3-D) imaging is demonstrated using an electronically controlled Liquid Crystal (LC) optical lens to accomplish a no-moving parts depth section scanning in a modified commercial 3-D confocal microscope. The proposed microscopy system within aberration limits has the potential to eliminate the sample or objective motion-caused mechanical forces that can distort the original sample structure and lead to imaging errors. A signal processing method for realizing high resolution three dimensional (3-D) optical imaging using diffraction limited low resolution optical signals is also proposed.

The ultraviolet (UV) spectrum has been known to cause damage to skin in varying degrees. UVB radiation (290-320 nm) in particular, has been proven to be highly mutagenic and carcinogenic in many animal experiments compared to either UVA or UVC. The alarming rate of increase in skin cancer incidence has prompted many investigators to pursue other alternatives to sunscreens including changes in lifestyle habits and dietary consumption in order to boost our efforts in tackling this widespread disease. Previous studies employing confocal reflectance, MTT assay and histology suggest that milk phospholipids may possess protective properties against UVB-mediated damage but the molecular mechanism for this effect remains unclear. This study aims to evaluate changes in cell morphology, apoptosis and p21 expression in tissue engineered epidermis to increase our understanding of the mechanisms behind the potential protective effects of milk phospholipids against UV-induced photodamage. Human skin tissue equivalents were incubated in either 1% milk phospholipid solution or maintenance media then exposed to 120 mJ/cm2 dose of 300 nm UVB after 24 hours. The upregulation of p21 protein in response to DNA damage was measured with Western blot and immunofluorescence microscopy and markers for apoptosis and hyperplasia were examined 24 hours after irradiation. Results revealed that p21 levels and the amount of apoptotic markers such as fragmented DNA and nuclear condensation were significantly reduced in UV-exposed tissues pre-incubated with milk phospholipids compared to levels seen in both the positive control and UV-exposed skin tissue not incubated with milk phospholipids. This decrease in p21 expression may imply a reduction in DNA damage 24 hours after UV exposure or a decrease in acquired photodamage at the outset. Milk phospholipid incubation however, induced an increase in epidermal thickening with or without UV exposure, which may imply induction of a protective mechanism to enhance the barrier properties of skin.

yes / Confocal microscopy is employed as a fast and non-invasive way to capture a sequence of images from different layers and membranes of the cornea. The captured images are used to extract useful and helpful clinical information for early diagnosis of corneal diseases such as, Diabetic Peripheral Neuropathy (DPN). In this paper, an automatic corneal subbasal nerve registration system is proposed. The main aim of the proposed system is to produce a new informative corneal image that contains structural and functional information. In addition a colour coded corneal image map is produced by overlaying a sequence of Cornea Confocal Microscopy (CCM) images that differ in their displacement, illumination, scaling, and rotation to each other. An automatic image registration method is proposed based on combining the advantages of Fast Fourier Transform (FFT) and phase correlation techniques. The proposed registration algorithm searches for the best common features between a number of sequenced CCM images in the frequency domain to produce the formative image map. In this generated image map, each colour represents the severity level of a specific clinical feature that can be used to give ophthalmologists a clear and precise representation of the extracted clinical features from each nerve in the image map. Moreover, successful implementation of the proposed system and the availability of the required datasets opens the door for other interesting ideas; for instance, it can be used to give ophthalmologists a summarized and objective description about a diabetic patient’s health status using a sequence of CCM images that have been captured from different imaging devices and/or at different times

Yes / The quantification of corneal endothelial cell (CEC) morphology using manual and semi-automatic software enables an objective assessment of corneal endothelial pathology. However, the procedure is tedious, subjective, and not widely applied in clinical practice. We have developed the CellsDeepNet system to automatically segment and analyse the CEC morphology. The CellsDeepNet system uses Contrast-Limited Adaptive Histogram Equalization (CLAHE) to improve the contrast of the CEC images and reduce the effects of non-uniform image illumination, 2D Double-Density Dual-Tree Complex Wavelet Transform (2DDD-TCWT) to reduce noise, Butterworth Bandpass filter to enhance the CEC edges, and moving average filter to adjust for brightness level. An improved version of U-Net was used to detect the boundaries of the CECs, regardless of the CEC size. CEC morphology was measured as mean cell density (MCD, cell/mm2), mean cell area (MCA, µm2), mean cell perimeter (MCP, µm), polymegathism (coefficient of CEC size variation), and pleomorphism (percentage of hexagonality coefficient). The CellsDeepNet system correlated highly significantly with the manual estimations for MCD (r = 0.94), MCA (r = 0.99), MCP (r = 0.99), polymegathism (r = 0.92), and pleomorphism (r = 0.86), with p

Corneal diseases are one of the major causes of visual impairment and blindness worldwide. Used for diagnoses, a laser confocal microscope provides a sequence of images, at incremental depths, of the various corneal layers and structures. From these, ophthalmologists can extract clinical information on the state of health of a patient’s cornea. However, many factors impede ophthalmologists in forming diagnoses starting with the large number and variable quality of the individual images (blurring, non-uniform illumination within images, variable illumination between images and noise), and there are also difficulties posed for automatic processing caused by eye movements in both lateral and axial directions during the scanning process. Aiding ophthalmologists working with long sequences of corneal image requires the development of new algorithms which enhance, correctly order and register the corneal images within a sequence. The novel algorithms devised for this purpose and presented in this thesis are divided into four main categories. The first is enhancement to reduce the problems within individual images. The second is automatic image classification to identify which part of the cornea each image belongs to, when they may not be in the correct sequence. The third is automatic reordering of the images to place the images in the right sequence. The fourth is automatic registration of the images with each other. A flexible application called CORNEASYS has been developed and implemented using MATLAB and the C language to provide and run all the algorithms and methods presented in this thesis. CORNEASYS offers users a collection of all the proposed approaches and algorithms in this thesis in one platform package. CORNEASYS also provides a facility to help the research team and Ophthalmologists, who are in discussions to determine future system requirements which meet clinicians’ needs. / The data and image files accompanying this thesis are not available online.

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Anthracene was attached to light activated, ruthenium-based DNA disruptors to probe their distribution in cancer cells. The objective of this research is to understand the photophysical properties (Chapter 2), photoreactivity toward DNA and proteins (Chapter 3), and localization within cancer cells (Chapter 4) of ruthenium complexes that demonstrate promise as photodynamic therapy (PDT) agents. [(AnthbpyMe)(bpy)Ru(dpp)]2+ (1) and [(AnthbpyMe)2Ru(dpp)]2+ (2) absorb visible light with metal-to-ligand charge transfer (MLCT) transitions at 459 nm (16,000 M-1 cm-1 ) and 461 nm (21,000 M-1 cm-1 ), respectively. These species exhibit 3 MLCT emissions at λem = 661 nm and λem = 663 nm for 1 and 2, respectively, while the anthracene show emissions at 450 – 560 nm. The anthracene unit(s) quench the 3 MLCT to give quantum yields (lifetime) of Φem = 0.0059 [398(1) ns] and Φem = 0.0011 [414(1) ns] for 1 and 2, respectively. Voltammetry shows an irreversible anthracene oxidation at 1.23 – 1.28 V, RuIII/II oxidation at 1.53 – 1.55 V, and quasi-reversible reduction couples attributed to dpp0/-1 at 0.98 V. DNA gel shift assays demonstrate that complexes 1 and 2 modify DNA in the presence and absence of 3 O2 upon light activation to convert supercoiled DNA to a mixture of open circular (OC) DNA and a species that exhibit sa distinctly different migration rate than either OC and linear DNA. Binding constants, Kb, for complexes 1 and 2, toward DNA are 3.50 × 105 (3.50 × 104 ) and 4.50 × 103 (4.50 × 102 ) respectively. SDS-PAGE assays show that the complexes 1 and 2 modify bovine serum albumin (BSA) through an 3 O2-dependent mechanism upon light iii activation. The localization and PDT potency of the anthracene-Ru-dpp complexes are tested against F98 cells, which are rat glioma cells that simulate the infiltrative patterns of growth in cancer. Confocal microscopy demonstrates that complexes 1 and 2 internalize and localize primarily along the cell membrane and associate with dot-like vesicles within the cytoplasm. Complexes 1 and 2 show IC50 values of 107 µM and 85 µM, respectively, after 15 min of drug exposure and 1 h of PDT-treatment (λPDT = 455 nm). / Ph. D.

The aim of this work is to enhance the detection and classification pipelines of an artificial intelligence (AI)-based decision support system (DSS) for diagnosing acanthamoeba keratitis (AK), a vision-threatening disease. The images used are taken with the in vivo confocal microscopy (IVCM) technique, a complementary tool for clinical assessment of the cornea that requires manual human analysis to support diagnosis. The DSS facilitates automated image analysis and currently aids in diagnosing AK. However, the accuracy of AK detection needs improvements in order to use it in clinical practice. To address this challenge, we utilize image brightness processing through multiscale retinex (MSR), and develop a custom-built image processing pipeline with deep learning model and rule-based strategies. The proposed pipeline replaces two deep learning models in original DSS, resulting in an overall accuracy improvement of 10.23% on average. Additionally, our improved pipeline not only enhances the original system’s ability to aid AK diagnosis, but also provides a versatile set of functions that can be used to create pipelines for detecting similar keratitis diseases.

Les neurones sont des cellules excitables capables de coder et transmettre l’information sous forme d’oscillations du potentiel membranaire. Cette activité électrique est produite par une modification des flux ioniques transmembranaires. Les neurones constituent un exemple d’oscillateur cellulaire dont la dynamique non linéaire permet l’apparition d’une activité électrique complexe. Dans ce système, les ions calciques sont des messagers intracellulaires importants. Ils servent de médiateur entre un signal électrique et un signal chimique, par une modulation de l’activité enzymatique de certaines protéines. Ils interviennent dans de nombreuses fonctions neuronales, dont l’excitabilité électrique. Un des mécanismes mis en place par les neurones pour contrôler l’homéostasie du calcium intracellulaire provient de protéines cytoplasmiques capables de lier les ions calciques. Ces protéines jouent un rôle de « tampon » du calcium. Cependant, toutes leurs fonctions n’ont pas encore été mises en évidence. C’est l’objectif de notre travail. Nous avons voulu comprendre le rôle joué par une protéine « tampon » particulière, la calrétinine, sur le mode de décharge électrique d’un neurone où elle est exprimée en abondance, le grain cérébelleux. Pour cela, nous avons utilisé une approche théorique et expérimentale. Au niveau théorique, nous avons élaboré un modèle mathématique de l’activité électrique du grain cérébelleux, prenant en compte la chélation du calcium intracellulaire. Il permet de clarifier le rôle de la chélation du calcium intracellulaire sur les oscillations du potentiel membranaire. La modélisation de l’activité électrique du grain cérébelleux repose sur le formalisme développé par Hodgkin et Huxley pour l’axone géant de calmar. Dans ce contexte, l’application de la conservation de la charge au circuit équivalent de la membrane cellulaire fournit un système d’équations différentielles ordinaires, non linéaires. Dès lors, notre modèle nous a permis d’étudier l’impact des variations de la concentration de chélateur calcique sur les oscillations du potentiel membranaire. Nous avons ainsi pu constater qu’une diminution de la concentration en chélateur calcique induisait une augmentation de l’excitabilité électrique du grain cérébelleux, sans altérer le régime d’oscillations. Par contre, en augmentant fortement la concentration en chélateur calcique, nous avons montré que le grain cérébelleux changeait de dynamique oscillatoire, montrant des transitions d’un mode de décharge périodique régulier vers des oscillations en salve du potentiel membranaire. Au niveau expérimental, nous avons vérifié les résultats prévus par le modèle théorique. Nous avons ainsi montré que des grains de souris transgéniques déficientes en calrétinine présentaient une excitabilité électrique accrue par rapport aux grains contrôles. Puis, en restaurant un niveau de chélation calcique normal dans ces grains, par perfusion intracellulaire de chélateur calcique, nous montrons qu’ils retrouvent un niveau d’excitabilité normal. Ensuite, nous avons introduit dans des grains cérébelleux de souris sauvages, une forte concentration en chélateur calcique exogène. Conformément aux résultats théoriques, nous avons pu observer des transitions vers des oscillations en salve du potentiel membranaire. Enfin, nous avons montré que l’absence de calrétinine affecte les paramètres morphologiques du grain cérébelleux des souris transgéniques déficientes en calrétinine. En conclusion, ces résultats suggèrent que le mode de décharge des cellules excitables peut être modulé d’une façon importante par les protéines liant le calcium. De ce fait, des changements dans le niveau d’expression et/ou dans la localisation subcellulaire des protéines liant le calcium pourraient aussi jouer un rôle critique dans la régulation de processus physiologiques contrôlés par l’excitabilité membranaire. De plus, les mécanismes que nous avons mis en évidence pourraient être à l’origine d’un nouveau principe de régulation de la signalisation dans les circuits neuronaux et pourraient jouer un rôle fonctionnel dans le contrôle du codage de l’information et de son stockage dans le système nerveux central.