Solid tumors can hijack many of the same programs used in neurogenesis to enhance tumor growth and metastasis, thereby generating a plethora of neurogenesis-related molecules including semaphorins Among them, we have identified Semaphorin7A (SEMA7A) in breast cancer We first used to the DA-3 mammary tumor model to determine the effect of tumor-derived SEMA7A on immune cells We found that tumor-derived SEMA7A can modulate the production of proangiogenic chemokines CXCL2/MIP-2 and CXCL 1, and prometastatic MMP-9 in macrophages We next aimed to determine the expression and function of SEMA7A in mammary tumor cells We found that SEMA7A is highly expressed in both metastatic human and murine breast cancer cells We show that both TGF-β and hypoxia elicits the production of SEMA 7 A in mammary cells SEMA7 A shRNA silencing in 4T1 cells resulted in decreased mesenchymal markers MMP-3, MMP-13, Vimentin and TGF-β) SEMA7A silenced cells show increased stiffness with reduced migratory and proliferative potential In vivo, SEMA7A silenced 4T1 tumor bearing mice showed decreased tumor growth and metastasis Genetic ablation of host-derived SEMA7A synergized to further decrease the growth and metastasis of 4T1 cells Our findings suggest novel functional roles for SEMA7A in breast cancer and that SEMA7A could be a novel therapeutic target to limit tumor growth and metastasis / Includes bibliography / Dissertation (PhD)--Florida Atlantic University, 2016 / FAU Electronic Theses and Dissertations Collection

Perfluoroalkyl acids (PFASs) are toxic pollutants ubiquitously found in the ecosystem. Recent investigations have focused on describing their environmental behavior and spreading. This includes transportation by water, where groundwater can continue to spread the contaminants a long time after the use has ended. This thesis surveys the existing literature on the reactions in soil that decides the presence and composition of PFASs in groundwater. A chemical groundwater investigation was recently done by Stockholm’s Environmental and Health Administration. The thesis presents a quantitative analysis of the PFASs’ content in Stockholm’s groundwater to verify if it conforms to the literature. A statistical analysis of the ratio between perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) is included to test if the PFAS composition in groundwater is influenced by soil reactions. The literature states that due to the high water solubility, low volatility and moderate adsorption, PFASs are likely to be encountered in groundwater. The adsorption depends on both PFASs’ and soil’s properties. The quantitative analysis confirms the influence of the PFASs’ properties in Stockholm’s groundwater, where both more short-chained PFASs and carboxylates are present. However, the analysis could not confirm the influence of the soil properties in adsorption at normal environmental conditions. The statistical analysis shows that the ratio of PFOS to PFOA is increased in groundwater in comparison to stormwater (p < 0.15). The increase cannot be explained by the hypothesis that the adsorption of PFAS governs this behavior, since PFOS is a sulfonate and longer than PFOA. An explanation is found in the degradation of precursors, which seems to contribute to PFOS concentrations in groundwater. This shows the important contribution of degradation of precursors to PFOS concentrations and motivates further investigations on the matter.

Explosive precursors and narcotic salts are chemicals contributing to an undesirabledevelopment of the Swedish society, both in terms of criminal activities and harm to the environment. Reducing the illegal use of these chemicals is important in the work towards a safer society. National Forensic Centre (NFC) is the state agency responsible for forensic investigations for the Swedish Police Authority. The Drug Analysis and ChemistryTechnology section at NFC were both in need for an accurate quantification method to determine the content of Cl in narcotic salts and explosive precursors. Nuclear magnetic resonance (NMR) spectroscopy was assessed to be suitable since a recently published article had shown applicability of 35Cl NMR on narcotic salts. The aim of the method was to find the most appropriate parameter settings for the compounds of interest, including operating frequency, 90° pulse length, number of scans, relaxation time, and relaxation delay. To ensure a reliable and accurate method, the following validation parameters were studied; linearity, limit of detection (LOD), limit of quantification (LOQ), intermediate precision, trueness, repeatability, and ruggedness. Dimethyl sulfoxide (d6-DMSO) was chosen as the preferredsolvent for the Drug Analysis section since it is a common solvent for their 1H-NMR analysis. For explosive precursors results showed advantages of using deuterium oxide (D!O) as solvent, considering accuracy, solubility and shorter analysis time.Concluding, the chosen criteria of signal-to-noise (S/N) ratio >6 resulted in an LOQ of around 0.15g/L, though this was dependent upon the number of scans utilized. Successful pulse length experiments determined exact 90° pulse lengths for each sample and solvent combination. The longitudinal relaxation time T1 was also successfully determined, and since it was multiplied with five to ensure complete relaxation to stable state the relaxation delay D1was assumed as an insignificant parameter for the determination of chloride. Quantification was based upon the pulse-length based concentration determination (PULCON) using an external standard. The ruggedness can be studied additionally by another experienced operator (since trueness was strongly dependent upon the preparation of the external standard solution). The method displayed good linearity over the mass range normally utilized in such quantifications. The conclusion drawn in the thesis is that the method shows great promise but additional analyzes are still required before implementation at NFC

This investigation deals with the preparations of cyclic organosilanes via two different types of organometallic precursors: borane adducts to chlorovinylsilanes and tertbutyllithium adducts to chlorovinylsilanes. The regiospecificity of the hydroboration of various types of boranes to chlorovinylsilanes was studied by three different methods. It was found that, by using bulky hydroborating agents, about 80% isomerically pure terminal borane adducts to chlorovinylsilanes could be obtained. While the adducts are potential precursors to silacyclopropanes, when these borane adducts were treated with bases such as sodium methoxide and methyl Grignard, no evidence for silacyclopropane formation was found.

The evolution of injection processes toward more fuel efficient and less polluting combustion systems tend to make them more prone to critical events such as Thermo-Acoustic Instabilities, Blow-Off and Flash-Back. Moreover, the addition of Di-Hydrogen as a secondary or as the main fuel is in discussion by aeronautical engines manufacturers. It drastically modifies the stability of the system and thus raise several interrogations concerning the multiplicity of its use. Being able to predict critical phenomena becomes a necessity in order to efficiently operate a system without having to pre-test every configuration and without sacrificing the safety of the user. Based on Deep Learning techniques and more specifically Speech Recognition, the following study presents the steps to develop a tool able to successfully detect and translate precursors of instability of an aeronautical grade swirled injector confined in a tubular combustion chamber. The promising results obtained lead to proposals for future transpositions to real-size systems. / Utvecklingen av injektionsprocesser mot mer bränsleeffektiva och mindre förorenande förbränningssystem, tenderar att göra dem mer benägna att utsättas för kritiska händelser som Thermo-Acoustic Instabilities, Blow-Off och Flash-Back. Dessutom diskuterar flygmotorkonstruktörer möjligheten att använda Dihydrogen som sekundärt eller som huvudbränsle. Det modifierar drastiskt systemets stabilitet och det väcker frågan hur man kan använda det effektivt. Att kunna förutsäga kritiska fenomen blir en nödvändighet för att använda ett system utan att behöva att på förhand testa varje konfiguration och utan att reducera användarens säkerhet. Baserat på Deep-Learning-tekniker och Speech-Recognition-tekniker, presenterar följande studie stegen för att utveckla ett verktyg som kan upptäcka och översätta föregångare till instabilitet hos en swirled flygmotorerinsprutningspump som är innesluten i en förbränningskammare. De lovande resultaten leder till idéer om hur man kan anpassa det här verktyg till ett system i verklig storlek.

The asthenosphere, a weak layer beneath the rigid lithosphere, plays a fundamental role in the operation of plate tectonics and mantle convection. While this layer is often characterized by low seismic velocity and high seismic attenuation, the global structure of the asthenosphere remains poorly understood. In this dissertation, twelve years of SS precursors reflected off the top and bottom of the asthenosphere, namely, the LAB and the 220-km discontinuity, are processed to investigate the boundaries of the asthenosphere at a global scale. Finite-frequency sensitivities are used in tomography to account for wave diffraction effects that cannot be modeled in global ray-theoretical tomography. Strong SS precursors reflected off the LAB and the 220-km discontinuity are observed across the global oceans and continents. In oceanic regions, the LAB is characterized by a large velocity drop of about 12.5%, which can be explained by 1.5%-2% partial melt in the oceanic asthenosphere. The depth of the Lithosphere Asthenosphere Boundary is about 120 km, and its average depth is independent of seafloor age. This observation supports the existence of a constant-thickness plate in the global oceans. The base of the asthenosphere is imaged at a depth of about 250 km in both oceanic and continental areas, with a velocity jump of about ∼ 7% across the interface. This finding suggests that the asthenosphere in oceanic and continental regions share the same defining mechanism. The depth perturbations of the oceanic 220-km discontinuity roughly follow the seafloor age contours. The 220-km topography is smoother beneath slower-spreading seafloors while it becomes rougher beneath faster-spreading seafloors. In addition, the roughness of the 220-km discontinuity increases rapidly with spreading rate at slow spreading seafloors, whereas the increase in roughness is much slower at fast spreading seafloors. This observation indicates that the thermal and compositional structures of seafloors formed at spreading centers may have a long-lasting impact on asthenospheric convections. In continental regions, a broad correlation is observed between the 220-km discontinuity depth structure and surface tectonics. For example, the 220-km discontinuity depth is shallower along the southern border of the Eurasian plate as well as the Pacific subduction zones. However, there is no apparent correlation between 3-D seismic wavespeed in the upper mantle and the depths of the 220-km discontinuity, indicating that secular cooling has minimum impact on the base of the asthenosphere. / Doctor of Philosophy / In classic plate tectonic theory, the outermost shell of the Earth consists of a small number of rigid plates (lithosphere) moving horizontally on the mechanically weak asthenosphere. In the classic half space cooling (HSC) model, the lithosphere is formed by gradual cooling of the hot mantle. Therefore, the thickness of the plate depends on the age of the seafloor. The problem with the HSC model is that bathymetry and heat flow measurements at old seafloors do not follow its predicted age dependence. A modified theory, called plate cooling model, can better explain those geophysical observations by assuming additional heat at the base of an oceanic plate with a constant thickness of about 125 km. However, such a constant-thickness plate has not been observed in seismology. In this thesis, the asthenosphere boundaries are imaged using a global dataset of seismic waves reflected off the Earth's internal boundaries. Strong reflections from the top of the asthenosphere are observed across all major oceans. The amplitudes of the SS precursors can be explained by 1.5%-2% of partial melt in the asthenosphere. The average boundary depths are independent of seafloor age, and this observation supports the existence of a constant-thickness plate in the global oceans with a complex origin. The 220-km discontinuity, also called the Lehmann Discontinuity, was incorporated in the Preliminary Reference Earth Model in the 1980's to represent the base of the asthenosphere. However, the presence and nature of this boundary have remained controversial, particularly in the oceanic regions. In contrast to many studies which suggest the 220-km discontinuity does not exist in the global oceans, SS precursors reflected from this interface are observed across the oceanic regions in this thesis. Furthermore, there is a positive correlation between the topography of the 220-km discontinuity and seafloor spreading rate. Specifically, the 220-km discontinuity is smoother beneath slower-spreading seafloors and much rougher beneath faster-spreading seafloors. In addition, the roughness increases faster at slowerspreading seafloors while much more gradual at faster-spreading seafloors. This indicates a close connection between seafloor spreading and mantle convections in the asthenosphere, and seafloors have permanent memories of their birth places. Different melting processes at slow and fast spreading centers produce seafloors with different physical and chemical properties, modulating convections in the asthenosphere and ultimately shaping the topography of the 220-km discontinuity. Reflections from the 220-km discontinuity are also observed across the global continental regions. In addition, the 220-km discontinuity beneath the continents is comparable to that under oceanic regions in terms of their average depth (∼ 250 km) and velocity contrast across the discontinuity (∼ 7%). In continental regions, there is a general connection between the 220-km depth structure and plate tectonics. For example, the boundary is shallower along the southern border of the Eurasian plate from the Mediterranean region to East Asia where mountain belts were formed as a result of collision between the Eurasian plate and the Nubian, Arabian and Indian plates. Depth perturbations of the 220-km discontinuity are also observed along the Pacific subduction zones including the Cascadia Subduction Zone, Peru-Chile Trench and Japan-Kuril Kamchatka Trench. In addition, depth anomalies are mapped in the interior of continents, for example, along the foothills of high topography in the interior of the Eurasian plate, which may be controlled by far-field convection associated with the convergent processes at the plate boundaries.

Significant progress in reducing the growth temperature of the SiC epitaxial growth became possible in the previous work by using new chloro-carbon epitaxial growth method. However, it was established that even in the new process, homogenous nucleation of Si in the gas phase limited the growth rate. In the present work, new chlorinated silicon precursor SiCl4 was investigated as a replacement for the traditional silicon precursor SiH4 during the low-temperature chlorocarbon epitaxial growth. The new process completely eliminated the homogenous nucleation in the gas phase. Growth rate of 5-6 μm/h was achieved at 1300°C compared to less than 3 μm/h in the SiH4-based growth. The growth dependence on the C/Si ratio revealed that the transition from the C-supply-limited to the Si-supply-limited growth mode takes place at the value of the C/Si ratio much higher than unity, suggesting that certain carbon-containing species are favorably excluded from the surface reactions in the new process. Morphology degradation mechanisms, which are unique for the lowtemperature growth, were observed outside the established process window. Prior to this work, it remained unclear if CH3Cl simply served as a source of Cl to suppress homogeneous nucleation in the gas phase, or if it brought some other unknown improvements. In this work true benefits of CH3Cl in providing unique improvement mechanisms have been revealed. It was established that CH3Cl provided a much wider process window compared to C3H8. In contrast, even a very significant supply of extra Cl from a chlorinated silicon precursor or from HCl during the C3H8-based growth could not provide a similar benefit. The combination of the chloro-carbon and the chloro-silane precursors was also investigated at conventional growth temperature. High-quality thick epitaxial layers, with the growth rate up to 100μm/h were obtained, and the factors influencing the growth rate and morphology were investigated. Extensive optical and electrical characterization of the low-temperature and the regular-temperature epitaxial layers was conducted. The device-quality of the lowtemperature chloro-carbon epilayers was validated for the first time since the development of the chloro-carbon epitaxial process in the year 2005 by fabricating simple Schottky diodes and investigating their electrical characteristics.

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