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Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by acute myelitis (AM) and optic neuritis (ON), especially clinically severe longitudinally extensive transverse myelitis (LETM) and simultaneous bilateral ON. Patients with recurrent AM especially LETM without ON, and patients with recurrent ON without AM may have disorders belonging to the spectrum of NMO, neuromyelitis optica spectrum disorders (NMOSD). NMO is likely autoimmune in nature as a significant proportion of patients are seropositive for aquaporin-4 (AQP4) autoantibodies. I studied the clinical features of local Chinese NMOSD patients and their AQP4 autoantibodies seropositivity rates of by indirect immunofluorescence using tissue slides containing primate cerebellum (tissued-based immunofluorescence assay) in patients with 1) NMO, 2) classical multiple sclerosis (CMS), 3) acute disseminated encephalomyelitis (ADEM), 4) single attack or relapsing AM, 5) single attack or relapsing ON, and 6) other neurological disorders. The results showed that NMOSD are severe CNS IDD affecting patients with a wide range of onset ages. Chinese NMOSD patients predominantly have relapsing NMO and relapsing LETM with severe attack of LETM and/or ON. The six-year mortality rate of patients with NMO or relapsing myelitis with LETM was about 12%. Two-thirds of patients have poor neurological outcome at a mean duration of 6.0 years. The results confirmed that AQP4 autoantibodies are specific for NMOSD, and detection of AQP4 autoantibodies is clinically useful for early diagnosis of NMOSD and distinction from CMS. I proceeded to study a cell-based immunofluorescence assay using transfected human embryonic kidney cells overexpressing human AQP4 on cell membrane and found that cell-based assay has higher sensitivity than tissue-based assay in detection of AQP4 autoantibodies in NMO (78% versus 61%). As our NMOSD patients frequently presented clinically with severe brainstem symptoms and signs and lesions in brainstem and other brain regions on magnetic resonance imaging (MRI), I studied the clinical and neuroradiological characteristics of Chinese NMOSD patients with brain involvement. I found that 59% of NMOSD patients have clinical and/or radiological evidence of brain involvement. Importantly, brainstem is the most frequently affected brain region and 24% of NMOSD patients had clinical manifestation of brainstem encephalitis. I also studied the pathogenicity of AQP4 autoantibodies in the absence of complement activation by passive transfer of IgG isolated from sera of NMOSD patients into mice pretreated with complete Freund’s adjuvant (CFA, containing heat-killed mycobacterium tuberculosis) and pertussis toxin (PTx). I observed that pretreatment with CFA and PTx led to breach of BBB in mouse, and IgG isolated from sera of NMOSD patients seropositive for AQP4 autoantibodies led to asymptomatic loss of AQP4 in gray and white matter in mouse spinal cord without inflammatory cell infiltration, demyelination or astrocytic loss in the absence of complement activation (human IgG cannot activate mouse complements). My findings support that 1) AQP4 autoantibodies binding to astrocytic AQP4 per se can cause downregulation of AQP4 in the absence of complement activation, and 2) complement activation with resultant complement activation products play key roles in the inflammation, demyelination and astrocyte cytotoxicity in NMO. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Recent impactful advances in integrated photonics undoubtedly owe much to silicon and its associated enabling platform (SOI). Although silicon has proved to be an indispensable element in many photonic systems yet it seems that it is not the ultimate solution to address all the challenges facing the photonics community. Therefore, integration of silicon with other optical materials featuring diverse properties is highly desirable. Such integration will be conducive to platforms which are naturally more capable and are suited for implementation of a wider range of optical devices and diverse functionalities. This dissertation is dedicated to design and implementation of integrated optical elements for hybrid material platforms. The basic theoretical foundation of integrated photonics is laid out in Chapter 2. In Chapter 3, an interlayer grating coupler for a specific hybrid material platform is designed, and demonstrated. Considering the fact that in almost all integrated photonic platforms, fabrication imperfections lead to an unpredictable shift in the wavelength of operation of individual devices, post fabrication tuning/trimming is inevitable. A number of widely used post fabrication trimming/tuning methods are briefly reviewed in Chapter 4 with special emphasis on a method based on electron beam exposure. In Chapter 5, an ultra-fast, low-power, and self-trimmable electro-optic modulator in demonstrated on a Si-based multilayer platform. Due to its remarkable optical and electronic properties, graphene has become a valuable material for opto-electronic applications. Integration of this novel 2D material with SOI platform is investigated in Chapter 6. Graphene-based electro-optic modulation through absorption and refractive-index change is successfully demonstrated using electrostatic gating mechanism. Chapter 7 is devoted to demonstration of a field-programmable 2 by 2 optical switch on a vertically stacked Si/SiO2/SOI platform. In Chapter 8, the peak-dragging phenomenon in a nanobeam photonic crystal cavity is studied. The optical bistability associated with this nonlinear phenomenon is of great interest for all-optical processing and sensing application. Future directions of this thesis are also discussed in the last Chapter.

A distributed fiber optic intrusion sensor capable of detecting intruders from the pressure of their weight on the earth's surface was investigated in the laboratory and in field tests. The presence of an intruder above or in proximity to the buried sensor induces a phase shift in light propagating along the fiber which allows for the detection and localization of intrusions. Through the use of an ultra-stable erbium-doped fiber laser and phase sensitive optical time domain reflectometry, disturbances were monitored in long (several km) lengths of optical fiber. Narrow linewidth and low frequency drift in the laser were achieved through a combination of optical feedback and insulation of the laser cavity against environmental effects. The frequency drift of the laser, characterized using an all-fiber Mach Zehnder interferometer, was found to be less than 1 MHz/min, as required for operation of the intrusion detection system. Intrusions were simulated in a laboratory setting using a piezoelectric transducer to produce a controllable optical phase shift at the 2 km point of a 12 km path length. Interrogation of the distributed sensor was accomplished by repetitively gating light pulses from the stable laser into the sensing fiber. By monitoring the Rayleigh backscattered light with a photodetector and comparing traces with and without an induced phase shift, the phase disturbances were detected and located. Once the feasibility of such a sensor was proven in the laboratory, the experimental set up was transferred to Texas A&M's Riverside Campus. At the test site, approximately 40 meters of fiber optic cable were buried in a triangle perimeter and then spliced into the 12 km path length which was housed inside the test facility. Field tests were conducted producing results comparable to those found in the laboratory. Intrusions over this buried fiber were detectable on the φ-OTDR trace and could be localized to the intrusion point. This type of sensor has the potential benefits of heightened sensitivity, covertness, and greatly reduced cost over the conventional seismic, acoustic, infrared, magnetic, and fiber optic sensors for monitoring long (multi-km) perimeters.

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<p>The ability to interrogate structure-function photophysical properties on lanthanide-doped nanoscale materials will define their utility in next-generation applications and devices that capitalize on their size, light-conversion efficiencies, emissive wavelengths, syntheses, and environmental stabilities. The two main topics of this dissertation are (i) the interrogation of laser power-dependent quantum yield and total radiant flux metrics for a homogeneous, solution phase upconversion nanocrystal composition under both continuous wave and femtosecond-pulsed excitation utilizing a custom engineered absolute measurement system, and (ii) the synthesis, characterization, and power-dependent x-ray excited scintillation properties of [Y₂O₃; Eu] nanocrystals, and their integration into a fiber-optic radiation sensing device capable of in vivo dosimetry.</p><p>Presented herein is the laser power-dependent total radiant flux and absolute quantum yield measurements of homogeneous, solution-phase [NaYF₄; Yb (15%), Er (2%)] upconversion nanocrystals, and further compares the quantitative total radiant flux and absolute quantum yield measurements under both 970 nm continuous-wave and 976 nm pulsed Ti-Sapphire laser excitation (140 fs pulse-width, 80 MHz). This study demonstrates that at comparable excitation densities under continuous-wave and fs-pulsed excitation from 42 - 284 W/cm<super>2</super>, the absolute quantum yield, and the total radiant flux per unit volume, are within a factor of two when spectra are integrated over the 500 - 700 nm wavelength regime. This study further establishes the radiant flux as the true unit of merit for quantifying emissive output intensity of upconverting nanocrystals for application purposes, especially given the high uncertainty in solution phase upconversion nanocrystal quantum yield measurements due to their low absorption cross-section. Additionally, a commercially available bulk [NaYF₄; Yb (20%), Er (3%)] upconversion sample was measured in the solid-state to provide a total radiant flux and absolute quantum yield standard. The measurements were accomplished utilizing a custom-engineered, multi-detector integrating sphere measurement system that can measure spectral sample emission in Watts on a flux-calibrated (W/nm) CCD-spectrometer, enabling the direct measurement of the total radiant flux without need for an absorbance or quantum yield value. </p><p>Also presented is the development and characterization of a scintillating nanocrystalline composition, [Y_2-xO₃; Eu_x, Li_y], in which Eu and Li dopant ion concentrations were systematically varied in order to define the most emissive compositions under specific x-ray excitation conditions. It is shown that these optimized [Y_2-xO₃; Eu_x, Li_y] compositions display scintillation responses that: (i) correlate linearly with incident radiation exposure at x-ray energies spanning from 40 - 220 kVp, and (ii) manifest no evidence of scintillation intensity saturation at the highest evaluated radiation exposures [up to 4 Roentgen per second]. X-ray excitation energies of 40, 120, and 220 kVp were chosen to probe the dependence of the integrated emission intensity upon x-ray exposure-rate in energy regimes where either the photoelectric or the Compton effect governs the scintillation mechanism on the most emissive [Y_2-xO₃; Eu_x, Li_y] composition, [Y_1.9O₃; Eu_0.1, Li_0.16]. These experiments demonstrate for nanoscale [Y_2-xO₃; Eu_x], that for comparable radiation exposures, when scintillation is governed by the photoelectric effect (120 kVp excitation), greater integrated emission intensities are recorded relative to excitation energies where the Compton effect regulates scintillation (220 kVp excitation). </p><p>The nanoscale [Y_1.9O₃; Eu_0.1, Li_0.16] was further exploited as a detector material in a prototype fiber-optic radiation sensor. The scintillation intensity from a [Y_1.9O₃; Eu_0.1, Li_0.16]-modified optical fiber tip, recorded using a CCD-photodetector or a Si-photodiode, was correlated with radiation exposure using a Precision XRAD 225Cx small-animal image guided radiation therapy (IGRT) system, an orthovoltage cabinet-irradiator, and a clinical X-ray Computed Tomography (CT) machine. For all x-ray energies tested from 80 - 225 kVp, this near-radiotransparent device recorded scintillation intensities that tracked linearly with total radiation exposure, highlighting its capability to provide alternately accurate dosimetry measurements for both diagnostic imaging and radiation therapy treatment. Because Si-based CCD and photodiode detectors manifest maximal sensitivities over the emission range of nanoscale [Y_1.9O₃; Eu_0.1, Li_0.16], the timing speeds, sizes, and low power-consumption of these devices, coupled with the detection element's linear dependence of scintillation intensity with radiation dose, demonstrates the opportunity for next-generation radiation exposure measuring devices for in/ex vivo applications that are ultra-small, inexpensive, and accurate.</p> / Dissertation

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Thesis (MScEng)--University of Kwa-Zulu Natal, 2011. / ENGLISH ABSTRACT: This research investigates the collection of concentrating solar energy and its transmission through optical fibres for use in high temperature applications such as lunar in-situ resource utilisation (ISRU) programmes, solar power generation and solar surgery. A prototype collector, known as the Fibre Optic Concentrating Utilisation System (FOCUS), has been developed and is capable of delivering high energy fluxes to a remote target. Salient performance results include flux concentrations approaching 1000 suns with an overall optical efficiency of 13%, measured from the inlet of the collector to the fibre outlet. The system comprises a novel solar concentrator designed to inject solar energy into a four metre long fibre optic cable for the transmission of light to the target. A nonimaging reflective lens in the form of a 600 mm diameter ring array concentrator was chosen for the collection of solar energy. Advantageous characteristics over the more common parabolic dish are its rearward focusing capacity and single stage reflection. The ring array comprises a nested set of paraboloidal elements constructed using composite material techniques to demonstrate a low-cost, effective fabrication process. At concentrator focus, a fibre optic cable of numerical aperture 0.37 is positioned to transport the highly concentrated energy away from the collector. The cable is treated to withstand UV exposure and high solar energy flux, and allows flexibility for target positioning. A computational analysis of the optical system was performed using ray tracing software, from which a predictive model of concentrator performance was developed to compare with experimental results. Performance testing of FOCUS was conducted using energy balance principles in conjunction with a flat plate calorimeter. Temperatures approaching 1500°C and flux levels in the region of 1800 suns were achieved before injection to the cable, demonstrating the optical system‟s suitability for use in high flux applications. During testing, peak temperatures exceeding 900°C were achieved at the remote target with a measured flux of 104 W/cm2 at the cable outlet. The predicted optical efficiency was 22%, indicating that further refinements to the ray trace model are necessary, specifically with regard to losses at the inlet to the cable. FOCUS was able to demonstrate its usefulness as a test bed for lunar in-situ resource utilisation technologies by successfully melting a lunar soil simulant. The system permits further terrestrial-based ISRU research, such as oxygen production from regolith and the fabrication of structural elements from lunar soil. / Sponsored by the Centre for Renewable and Sustainable Energy Studies

This study aimed to better understand the clearance of myelin debris during Wallerian degeneration in the goldfish visual paths. Myelin debris was first examined immunohistochemically in the presence or absence of regenerating axons. From these preliminary experiments it was apparent that the clearance of myelin debris was not affected by regenerating axons and that the debris was removed in a differential pattern along the visual pathway. Specifically, in the distal stump of the nerve as well as in the optic tract, myelin debris had been effectively cleared by one-month postoperative, while in the cranial segment of the nerve debris persisted for at least 6 weeks after injury. The differential pattern of myelin debris in the optic nerve and tract was then analyzed qualitatively and quantitatively using thick and thin plastic sections at various time points during regeneration. The results suggested that highly activated peripheral macrophages were responsible for the effective clearance of myelin in the distal nerve stump. In the optic tract a number of cellular properties, including their unique population of astrocytes may have enhanced the rate of debris clearance. By contrast, in the cranial segment of the nerve persistent debris was found both intracellularly in phagosomes and extracellularly, suggesting that the resident phagocytes were deficient in effecting both phagocytosis and emigration. Deficient phagocytosis may be a result of the production of anti-inflammatory cytokines in this region, while the failure to emigrate is most likely due to the rigid network of astrocytes in the nerve.