Thesis (Ph. D.)--University of Chicago, August 1999. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph.D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (November 15, 2006) Vita. Includes bibliographical references.

Transition metal dichalcogenides (TMDs) have displayed a host of novel physical phenomena, which opens-up promising future applications in electronics, optoelectronics, spintronics and valleytronics. However, the high defect density of 10¹² - 10¹³ cm-² in commercially available TMDs may hinder the observation of their intrinsic properties. In this thesis, the defect density of MoSe₂ and WSe₂ has been reduced by ~10x - 1000x using flux method. The reduced defect denstiy of MoSe₂ and WSe₂ enables to observe optical and electrical properties approaching their intrinsic properties.First of all, photocurrent measurements on the ultra-clean WSe₂ unveil the effect of point defects on photo-response. Substantial improvement of AC photocurrent in the ultra-clean WSe2 indicates that free carriers are likely to non-radiatively decay at atomic defects at room temperature. Then, time-resolved photoluminescence measurements on the ultra-clean MoSe₂ samples allow for direct determination of both the intrinsic (radiative) and defect-dependent (non-radiative) lifetimes of trions. In the cleanest MoSe₂, the trion quantum yield approaches unity. The long lifetime of 230 ps of trions allows direct observation of their diffusion, conclusively demonstrating that trions are free particles. Both the long radiative and non-radiative lifetime of trions can be attributed to Pauli blocking effects. Morover, transport measurements of ultra-clean WSe2 provide Hall mobility exceeding 10,000 cm²V-¹s-¹ and long mean free path over 200 nm, which are nearly three times higher than those in previous study. This improved mobility and mean free path in the ultra-clean WSe₂ indicate that the electrical properties have been limited by defect scattering. Finally, WSe₂ has been a decent platform to generate single photon emitters. However, the microscopic origin of the single photon emitter has been debated. From power- and gate-dependent photoluminescence of ultra-clean WSe₂, emerging defect bound excitons are observed, which is likely formed from the interaction between donor defects and excitons.

This dissertation presents the results of an investigation into the performance characteristics of a unique hemispherical SPECT (single-photon emission computed tomography) imaging system capable of producing three-dimensional (3D) tomographic images of the human brain. The system is completely stationary and collects all necessary views of the patient simultaneously, with no system motion. The imager consists of twenty small (10cm x 10cm crystal area), digital gamma cameras arranged in a hemispherical pattern around the patient's head and a hemispherical lead aperture. The hemispherical aperture is positioned between the cameras and the head and contains a large number of pinholes; in this way each camera sees a number of overlapping pinhole projections of the radioactive distribution within the patient's brain. The initial investigation of the performance characteristics of a 3D SPECT system of this design were carried out using a computer simulation in which effects due to radiometry, finite pinhole size, finite detector resolution, photon noise, and object attenuation were included. We used a digital 3D brain phantom as the test object and an iterative search algorithm to perform the reconstructions. The simulations were used to compare the performance of a variety of system configurations. Based upon the results of the simulation study, we constructed a laboratory prototype of the 3D SPECT system, which we used to further characterize the expected performance of a clinical imaging system of the same design. Prior to collecting SPECT data we calibrated the imaging system, which required that we efficiently measure and store the spatially variant system response function. These calibration data were then included in the reconstructions of the SPECT phantoms that we imaged. A number of different SPECT phantoms were imaged to demonstrate the system performance. We measured a reconstructed spatial resolution of 4.8mm full-width at half-maximum and a full-system sensitivity of 36cps/μCi, where both values were measured for a point source in air located at the center of the field of view. We also describe an analysis that we performed to determine the equivalent, non-multiplexed system sensitivity; using this method, we found that the equivalent sensitivity was 79% of the measured value for the system configuration and the particular task that we investigated.

Seizures are thought to arise primarily from the cerebral cortex. However, the propagation and behavioral manifestations of seizures involve a network of both cortical and subcortical structures. The medial thalamus and upper brainstem reticular formation are crucial areas for the maintenance of normal consciousness. Bilateral involvement of these structures may be responsible for loss of consciousness during partial seizures. Therefore, we sought to investigate the role of the medial thalamus and brainstem in seizures. We performed SPECT ictal-interictal difference imaging co-registered with high-resolution MRI scans to localize regions of cerebral blood flow changes in patients undergoing inpatient monitoring for epilepsy. Ictal-interictal SPECT scans from 43 seizures in 40 patients were analyzed. The medial thalami showed SPECT difference imaging changes of >20% in 18 patients. Of patients with medial thalamic changes, the majority (13 of 18) had seizure onset in the temporal lobe, while only 1 had confirmed onset in extratemporal structures, and the remainder were non-localized. In contrast, in the 22 patients without >20% SPECT changes in the medial thalami, 6 had extratemporal onset, 6 had temporal onset, and the remainder were non-localized. In patients with temporal lobe seizures, the side of greater medial thalamic and brainstem reticular formation involvement was strongly related to SPECT injection timing such that there was a sequential pattern of ipsilateral followed by contralateral changes. Brainstem structures showed >20% SPECT changes in 27 of 43 seizures with no clear relation to temporal or extratemporal onset. We conclude that the medial thalamus is preferentially involved in seizures arising from the temporal lobes, possibly reflecting the strong connections between limbic temporal structures and the medial thalamus. Sequential involvement of ipsilateral followed by contralateral structures in the medial thalamus and upper brainstem may explain how seizures produce peri-ictal loss of consciousness despite incomplete involvement of the cerebral cortex.

The possibilities and implications of photons within the infrared, visible, and ultraviolet behaving as sources of intracellular and intercellular communication and information were investigated experimentally for melanoma cells during the 24 hrs following removal from incubation. Specific wavelengths during different intervals were associated with specific classes of biomolecules that were predicted based on the physical properties associated with their amino acid sequences. Application of a specific intensity and physiologically patterned magnetic field predicted from a model that applied the concept of magnetic moment to the whole cell resulted in photon emissions. They were detected at distances sufficient to allow intercellular communication. The occurrence of macroscopic entanglement or non-locality was shown between two loci of where simple chemically-based photons emissions were generated. Within all three experiments there was marked quantitative congruence between the energies associated with the power density of the photon emissions and the physicochemical variables involved with their reduction. These results indicate that photon emissions coupled with classic biomolecular pathways and processes may behave as intra- and inter-cellular sources of information that could control the complex dynamics of cells. The effect may not depend upon locality but exhibit non-local characteristics.

Thesis (Ph. D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2005" Includes bibliographical references.

The purpose of this thesis is to investigate the nonlinear phenomena known as doubly-stimulated, non-degenerate two-photon emission (ND-2PE) in Gallium Arsenide (GaAs). 2PE refers to the simultaneous emission of two-photons as electrons move from the conduction band in a direct gap semiconductor to the valence band. Following the same path for describing one-photon emission (1PE) we describe 2PE as a product of the irradiance, and the negative of the loss which in this case is two-photon absorption, , the negative coming from the population inversion. We attempt to observe 2PE by using a frequency non-degenerate pump-probe experiment in which a third beam optically excites a 4 µm thick GaAs sample. We use nondegenerate beams in hopes of utilizing the 3-orders of magnitude enhancement seen in twophoton absorption (2PA) by going to extreme nondegeneracy (END) to enhance 2PE. GaAs is chosen due to the availability of the appropriate wavelengths, the maturity of the GaAs technology, its use in optoelectronic devices and its ability to be electrically pumped. During the experimental development we learn how to effectively etch and manipulate thin GaAs samples and model the transmission spectrum of these samples using thin film transmission matrices. We are able to match the measured transmission spectrum with the theoretical transmission spectrum. Here we etch the bulk GaAs left on the sample leaving only the 4 µm thickness of molecular beam epitaxial grown GaAs plus additional layers of aluminum gallium arsenide (AlGaAs). These samples were grown for us by Professor Gregory Salamo of the University of Arkansas. iv Using the pump-probe experiment on the 4 µm GaAs sample, we measure the change of the 2PA due to the presence of optically excited carriers. The goal is to reduce the 2PA signal to zero and then invert the 2PA signal indicating an increase in transmission indicative of 2PE when the population is inverted. Our results show that we achieve a 45% reduction in the 2PA signal in a 4 μm thick GaAs sample due to the excited carriers. Unfortunately, we currently cannot experimentally determine whether the reduction is strictly due to free-carrier absorption (FCA) of our pump or possibly due to a change in the two-photon absorption coefficient. We measure the transmission of various wavelengths around the bang gap of GaAs as a function of excitation wavelength and achieve a transmittance of ~80% which we attribute to possibly be one photon gain (1PG) at 880 nm. We also go to cryogenic temperatures to concentrate the carriers near the bottom of the conduction band and improve the theoretical gain coefficient for 2PE. Unfortunately, we do not observe a measurable change in 2PA with the addition of optically excited carriers. Along with FCA of our infrared pump we suspect that the difficulties in this first set of experiments are also a result or radiative recombination due to amplified spontaneous emission reducing our free carrier density along with the fact that 4 m is too thick for uniform excitation. We now have 1 m samples from Professor Gregory Salamo which we hope will give better and more definitive results

The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Imaging of αvβ3 expression could potentially be used as a biomarker and an early indicator of efficacy of antiangiogenic treatments at a molecular level. Research efforts have mainly focused on the development of RGD-based radiolabelled αvβ3 inhibitors suitable for PET and SPECT imaging modalities that, owing to their high sensitivity, represent the most powerful tool for monitoring in vivo tumour angiogenesis. The aim of this multidisciplinary project was the design, synthesis and biological evaluation of novel αvβ3 ligands as molecular imaging probes. Three classes of integrin antagonists were designed: 1) triazole-based RGD mimetics that can be isotopically-labelled with tritium, fluorine and iodine radioisotopes by means of highly practical procedures, 2) RGD peptidomimetics incorporating the metabolically stable 2,2,2-trifluoroethylamine function as a peptide bond bioisostere and 3) RGD cyclopeptides conjugated with FDR, a novel prosthetic group allowing glycosylation and 18F-fluorination of aminooxy-functionalised molecules in one synthetic step. RGD-based strategies have also been used for selective tumour delivery of chemotherapeutic agents. A number of cytotoxic drugs have been conjugated to RGD peptides, providing experimental evidence that αvβ3 targeted chemotherapy strategies could be used as a powerful tool to reduce the toxicity and augment the therapeutic window of existing cytotoxic agents. In this work, we described the rational design of a novel targeted cytotoxic conjugate containing a triazole-based RGD peptidomimetic as tumour-homing motif of the potent antimitotic agent, paclitaxel. Preliminary in vitro studies were performed to assess the therapeutic potential of this targeted cytotoxic construct.

Thesis (MScMedSC (Medical Imaging and Clinical Oncology. Nuclear Medicine))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Single photon emission computed tomography (SPECT) with a superior contrast resolution has been shown to be more sensitive and specific with a lower nondiagnostic rate than planar imaging in many nuclear medicine studies but it is still not being routinely implemented in V/Q studies at many centres including Tygerberg Hospital. There are many studies on V/Q SPECT using Technegas as a ventilation agent but very limited studies available on 81m Kr gas. Aim: To clinically compare conventional planar and SPECT V/Q imaging using 81mKr gas in the diagnosis of pulmonary embolism, with CTPA as the gold standard. Patients and Methods: All patients referred with clinical suspicion of pulmonary embolism were assessed. The inclusion criteria were normal chest radiograph, normal renal function and no contrast allergy. Exclusion criteria were age below 18 years old, pregnancy, abnormal chest radiograph, abnormal serum creatinine/urea levels and unstable patients. A Well’s score was assigned to each enrolled patient. Perfusion scintigraphy was performed after intravenous injection 125 MBq of 99mTc MAA. Ventilation scintigraphy was performed with 81mKr gas. On a dual head camera, SPECT was done before planar acquisition, while perfusion was done before ventilation imaging in the same position. Planar V/Q images consisted of 6 standard views. All V/Q SPECT images were reconstructed using ordered-subset expectation-maximization (OSEM) algorithm and a post-reconstruction 3D Butterworth filters were applied. V/Q Planar and V/Q SPECT images were later evaluated and reviewed separately and reported based on recent EANM guidelines blinded to the CTPA results. All patients underwent multi-slice CTPA examinations on a 40-detector row scanner. The images were later assessed and reported blinded to the V/Q results. Statistical analysis was done using the Fisher exact test for comparison of categorical variables and the one-way ANOVA for continuous variables (p<0.05 was significant). Results: A total of 104 consecutive patients were referred with clinical suspicion of pulmonary embolism. Seventy-nine patients were excluded from this study mostly due to abnormal serum creatinine/urea levels. Only 25 patients were included in this study, with a mean age of 48 ± 19 years, and 64% being females. When compared to CTPA as gold standard, the prevalence of PE was 16% [5% – 37% at 95% CI], sensitivity 75% [21% – 99% at 95% CI], specificity 90% [68% – 98% at 95% CI], positive predictive value 60% [17% – 93% at 95% CI], negative predictive value 95% [73% – 100% at 95% CI] and diagnostic accuracy 88% [69% – 97%at 95% CI] for both V/Q Planar and SPECT. V/Q Planar showed a lower reader confidence i.e. could only clearly resolve 72% of cases compared to V/Q SPECT, which could precisely interpret all cases, showed more and better delineated mismatch vs match and segmental vs non-segmental defects. All patients who were scored as PE unlikely on Wells’ score (4) had PE ruled out on CTPA (p=0.04581) as well as 89% of patients on V/Q SPECT and V/Q Planar. Conclusion: Based on this study, V/Q Planar and V/Q SPECT have a similar diagnostic performance in patients with a normal or near normal chest X-rays. / AFRIKAANSE OPSOMMING: Enkelfoton emissie rekenaartomografie (EFERT) met beter kontrasresolusie is bewys om meer sensitief en spesifiek met ‘n laer nie-diagnostiese opbrengs as planare beelding in verskeie kerngeneeskunde ondersoeke te wees. In Tygerberg Hospitaal, soos in verskeie ander sentra, word dit egter steeds nie roetineweg vir ventilasie-perfusiestudies (V/Q) geïmplementeer nie. Daar is verskeie EFERT V/Q studies met Technegas as ventilasie agens, maar beperkte studies met 81m Kr gas beskikbaar. Doel: Om konvensionele planare en EFERT V/Q beelding vir die diagnose van pulmonale embolisme met mekaar te vergelyk, met rekenaartomografie pulmonale angiografie (RTPA) as goue standaard. Pasiënte en Metodes: Alle pasiënte wat met ‘n kliniese vermoede van pulmonale embolisme verwys is, is geevalueer. Die insluitingskriteria was ’n normale borskas Xstraal, normale nierfunksie en geen kontrasallergie nie. Uitsluitingskriteria was pasiënte jonger as 18 jaar, swanger pasiënte, abnormale borskas X-straal, abnormale serum kreatinien / ureumvlakke en onstabiele pasiënte. ’n Wells telling is vir elke pasiënt wat in die studie ingesluit is, bepaal. Perfusiebeelding is uitgevoer na die intraveneuse toediening van 125 MBq 99mTc MAA. Ventilasiestudies is gedoen met 81mKr gas. Die V/Q EFERT studies is voor die planare beelding met ’n dubbelkop gammakamera uitgevoer. Perfusiebeelding is voor die ventilasie in dieselfde posisie verkry. V/Q planare beelding het bestaan uit 6 standaard beelde. Alle V/Q EFERT is met “ordered-subset expectationmaximization” (OSEM) algoritmes verwerk, en post-rekonstruksie 3D Butterworth filters is toegepas. V/Q planare en V/Q EFERT beelding is later afsonderlik en sonder RTPA inligting volgens onlangse EANM riglyne evalueer en gerapporteer. ‘n Veelsnit RTPA met ‘n 40 snit skandeerder is op alle pasiënte uitgevoer. Die beelde is later beoordeel en gerapporteer sonder inagneming van die V/Q beeldingsresultate Statistiese verwerking is gedoen met die Fisher presisietoets vir vergelyking van kategoriese veranderlikes en die eenrigting ANOVA vir kontinue veranderlikes (p<0.05 is statisties betekenisvol). Resultate: ‘n Totaal van 104 opeenvolgende pasiënte met ‘n kliniese vermoede van pulmonale embolisme is verwys. Nege-en-sewentig pasiënte is uitgesluit, in die meeste gevalle as gevolg van abnormale serum kreatinienvlakke. Slegs 25 pasiënte is ingesluit, met ’n gemiddelde ouderdom van 48 ± 19 jaar, en 64% vroue. In vergelyking met RTPA as goudstandaard, was die prevalensie van PE 16% [5% – 37% met 95% VI], sensitiwiteit 75% [21% – 99% met 95% VI], spesifisiteit 90% [68% – 98% met 95% VI], positiewe voorspellingswaarde 60% [17% – 93% met 95% VI], negatiewe voorspellingswaarde 95% [73% – 100% met 95% VI] en diagnostiese akkuraatheid van 88% [69% – 97% met 95% VI] vir beide planare en EFERT V/Q beelde. V/Q planare beelde het ‘n laer lesersvertroue getoon, nl. dat slegs 72% van gevalle opgelos kon word relatief tot V/Q EFERT beelde, wat in alle gevalle presies geïnterpreteer kon word, met meer en beter omskrewe nie-ooreenstemmende teenoor ooreenstemmende en segmentele teenoor nie-segmentele defekte. In alle pasiënte met ‘n Wells puntetelling van 4 is PE met die RTPA uitgeskakel (p=0.04581), terwyl dit in 89% van pasiënte met V/Q EFERT en planare beelde uitgeskakel is. Gevolgtrekking: Gebaseer op hierdie studie het V/Q planare en EFERT beelding ‘n ooreenstemmende diagnostiese prestasie in pasiënte met ’n normale of naby normale borskas X-straal.