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Insights into the Isoprene Photochemical Cascade
Get PDFIsoprene emissions are the single largest source of non-methane reduced carbon to the atmosphere. Proper simulation of the effect of its photooxidation on regional air quality and secondary organic aerosol formation requires detailed multi-generation and multi-phase photochemical mechanisms. In this work, I first demonstrate that CF3O- chemical ionization mass spectrometry (CIMS) is a powerful method to probe isoprene photochemical oxidation. Under high NOx, isoprene nitrates and their photochemical products are directly observed and quantified. As isoprene nitrates are critical to the impact of isoprene photochemistry on ozone, these observations provide an important constraint on the effect of isoprene emissions on air quality in polluted and biogenic rich regions (e.g., Southeastern United States). The use of tandem CIMS in association with isotopically labelled hydroxy radicals is used to identify dihydroxyepoxides as major products of isoprene photooxidation in low NOx conditions. This class of compounds may provide an important precursor for secondary organic aerosols under acidic conditions. The chemical mechanism derived from these laboratory observations is then incorporated in a chemical transport model to assess the impact of isoprene photooxidation on atmospheric chemistry. I examine how the photooxidation of isoprene impacts the budget of formic and acetic acids, two ubiquitous trace gases whose sources are poorly constrained. Comparison with observations from satellite, ground and aircraft platforms, reveal a major missing source that may originate from the aging of secondary organic aerosols. Finally, the consequences of the multi-scale interplay between NOx and isoprene photochemistry on the tropical budget of ozone are examined using forward and adjoint sensitivity simulations
Beyond the Standard Cosmology: Anisotropic Inflation and Baryophilic Dark Matter
Get PDFThis thesis discusses two topics in cosmology that resulted in two independent publications. The first topic concerns persistent anisotropy during inflation and the second topic concerns a model of baryophillic dark matter.
The motivation for the project contained within chapter one came from indications in the cosmic microwave background data that seemed to suggest that there may be a cosmologically preferred direction. Moira Gresham and I derived quantitative predictions about the signals one would observe in Cosmic Microwave Background data if isotropy is not assumed during inflation. We considered a particular example of a dynamical theory of anisotropic inflation that is characterized by a scalar field which is nonminimally coupled to an isotropy breaking abelian gauge field, thereby slowing the decay of the gauge field energy density.
The motivation for the project contained within chapter two came from the observation that the global symmetries B (baryon number) and L (lepton number) of the standard model Lagrangian must be broken by higher-dimensional operators at a very high scale. Pavel F. Perez, Mark B. Wise and I analyzed a model that explained the protection of these accidental global symmetries by promoting B and L to gauge symmetries. This model has a natural dark matter, candidate and we discuss the experimental constraints on the parameters in the theory.
Unexpected results are found in each chapter. For example, in chapter two, we find that the anisotropic contribution to the tensor power spectrum is suppressed with respect to that of the scalar power spectrum and, in chapter three, we show that a baryon asymmetry can be generated even within a model that has baryon number as a gauge symmetry.</p
Bridging the Gap: Elusive Explosions in the Local Universe
Get PDFFor centuries, we have known that our dynamic universe is adorned by cosmic fireworks: energetic and ephemeral beacons of light from a single star that are a million (nova) to a billion (supernova) times brighter than our sun. However, it had been an age-old conundrum that the brightest nova is approximately 1000 times fainter than than the faintest supernova; why should nature leave such a wide "gap"?
In search of an answer, I undertook three systematic surveys for my thesis. Since I was looking for transients fainter, faster and rarer than supernovae, I focused my search on galaxies in the local universe. We now have convincing evidence of multiple, distinct populations of rare transients bridging this "gap". Perhaps, we are witnessing new stellar physics --- shell detonations in ultra-compact white dwarf binaries, electron-capture supernovae, white dwarfs collapsing into neutron stars and birth of black-holes.
A small number of intensively followed-up discoveries of elusive transients sets the stage for population studies with the upcoming "Large Synoptic Survey Telescope". This effort works towards building a complete inventory of transients in the local universe (d < 200 Mpc). It better prepares us for the search for potential electromagnetic counterparts to events in the emerging fields of gravitational wave, neutrino and ultra high energy cosmic ray astronomy as these experiments are also limited to the local universe.</p
A Novel Experimental Study of a Valveless Impedance Pump for Applications at Lab-On-Chip, Microfluidic, and Biomedical Device Size Scales
Get PDFIn 1954, Gerhart Liebau demonstrated a simple valveless pumping phenomenon utilizing the periodic compression of a compliant tube and some systematic asymmetry to pump water out of a bucket. Liebau's goal was to explain peculiarities seen in the human circulatory system. In the years that have followed, the Liebau phenomenon has been studied in a variety of open and closed loop configurations, through experimental, computational, and analytical studies.
Recent advances in microfluidic and microelectromechanical systems (MEMS) technology have enabled a wide range of small scale engineering systems. The further development of many important systems is limited by the absence of an appropriate means of fluid transport. Valveless pumps based on the Liebau phenomenon show great promise, particularly in lab-on-chip (LOC), biological, and medical applications in which biocompatibility and the ability to move sensitive molecules without damage are key design requirements.
The purpose of this thesis is to synthesize previous studies of the Liebau phenomenon and produce the first extensive experimental study of a novel valveless pump at size scales and geometries that are relevant to lab-on-chip, microfluidic, and biomedical device applications. For the first time, detailed, dynamic pressure and flow data have been recorded during the operation of these valveless pumps for a large range of operating parameters. This dynamic data allowed us to identify new flow regimes and observe previously undocumented pump behaviors and performance. Parameters investigated include pump material properties and geometry, working fluid density and viscosity, pump excitation properties (amplitude, offset, location, and frequency), and flow loop/system properties. A critical relationship between the relative volumetric compliance of the valveless pump to the system it acts upon is identified, and the implications for practical implementation of valveless pumps at small size scales are discussed.</p
Hybrid Silicon Nanophotonic Devices: Enhancing Light Emission, Modulation, and Confinement
Get PDFSilicon has become an increasingly important photonic material for communications, information processing, and sensing applications. Silicon is inexpensive compared to compound semiconductors, and it is well suited for confining and guiding light at standard telecommunication wavelengths due to its large refractive index and minimal intrinsic absorption. Furthermore, silicon-based optical devices can be fabricated alongside microelectronics while taking advantage of advanced silicon processing technologies. In order to realize complete chip-based photonic systems, certain critical components must continue to be developed and refined on the silicon platform, including compact light sources, modulators, routers, and sensing elements. However, bulk silicon is not necessarily an ideal material for many active devices because of its meager light emission characteristics, limited refractive index tunability, and fundamental limitations in confining light beyond the diffraction limit.
In this thesis, we present three examples of hybrid devices that use different materials to bring additional optical functionality to silicon photonics. First, we analyze high-index-contrast silicon slot waveguides and their integration with light-emitting erbium-doped glass materials. Theoretical and experimental results show significant enhancement of spontaneous emission rates in slot structures. We then demonstrate the integration of vanadium dioxide, a thermochromic phase-change material, with silicon waveguides to form micron-scale absorption modulators. It is shown experimentally that a 2-µm long waveguide-integrated device exhibits broadband modulation of more than 6.5 dB at wavelengths near 1550 nm. Finally, we demonstrate polymer-on-gold dielectric-loaded surface-plasmon waveguides and ring resonators coupled to silicon waveguides with 1.0±0.1 dB insertion loss. The plasmonic waveguides are shown to support a single surface mode at telecommunication wavelengths, with strong electromagnetic field confinement at the polymer-gold interface. These three device concepts show that diverse materials can be integrated with silicon waveguides to achieve enhanced light emission, broadband modulation, and strong confinement, all while retaining the advantages of the silicon photonics platform.</p
Some New Aspects of Mass Equidistribution
Get PDFThis thesis presents two new results concerning the limiting behavior of families of automorphic forms. First, let F be a totally real number field of degree n, and let f traverse a sequence of nondihedral holomorphic eigencuspforms on GL(2,F) of trivial central character and full level. We show that the mass of equidistributes on the Hilbert modular variety as any one of the weight components of f tends to infinity. Our result answers affirmatively a natural analogue of a conjecture of Rudnick and Sarnak (1994). Our proof generalizes the argument of Holowinsky-Soundararajan (2008) who established the case F = Q. The essential difficulty in doing so is to adapt Holowinsky's bounds for the Weyl periods of the equidistribution problem in terms of manageable shifted convolution sums of Fourier coefficients to the case of a number field with nontrivial unit group.
Second, let f traverse a sequence of classical holomorphic newforms of fixed weight and increasing squarefree level q tending to infinity. We prove that the pushforward of the mass of f to the modular curve of level 1 equidistributes with respect to the Poincare measure. Our result answers affirmatively the squarefree level case of a conjecture spelled out by Kowalski, Michel, and VanderKam (2002) in the spirit of a conjecture of Rudnick and Sarnak (1994). Our proof follows the strategy of Holowinsky and Soundararajan (2008) who showed that newforms of level 1 and large weight have equidistributed mass. The new ingredients required to treat forms of fixed weight and large level are an adaptation of Holowinsky's reduction of the problem to one of bounding shifted sums of Fourier coefficients, a refinement of his bounds for shifted sums, an evaluation of the p-adic integral needed to extend Watson's formula to the case of three newforms where the level of one divides but need not equal the common squarefree level of the other two, and some additional technical work in the problematic case that the level has many small prime factors.</p
Microfluidics Platforms for Quantitative, Multiplexed Protein Detection
Get PDFThis thesis describes the development of microfluidic platforms that enable cheap, facile, rapid, and multi-parameter protein sensing. The first section of this work describes two strategies for high density DNA microarray patterning: microcontact printing and flow patterning. A protocol is provided for micron-scale alignment of multiple PDMS stamps to a single substrate, and a simple strategy to allow very low aspect-ratio stamping is enumerated.
The second section describes the formation of high density antibody microarrays using flow patterned DNA microarrays in conjunction with DEAL chemistry, and applies these microarrays to biological measurements. The platform’s performance is first characterized using a human chorionic gonadotropin assay, and is subsequently used to stratify 22 cancer patients from frozen serum samples by quantifying the levels of twelve serum proteins. A microfluidic plasma separation device is then detailed to allow for similar measurements from fresh finger pricks of blood.
The third section of this work outlines improvements to the flow patterning platform through two alternate schemes: covalent attachment and DMSO patterning. Both protocols are shown to dramatically increase the consistency of microarray elements across a single chip when compared to the initial method. Theoretical simulations are used to describe the mechanism by which DMSO enhances patterning consistency.
The fourth section describes the design and fabrication of a robotics system that is capable of autonomously interfacing and manipulating PDMS substrates, and its application to producing barcode microarrays. The resulting substrates show unprecedented consistency from chip to chip, and we demonstrate through massively parallel single-cell measurements that data derived from different substrates is statistically indistinguishable.
Finally, we introduce an integrated software and hardware package designed to facilitate and automate microfluidic control at the laboratory level. We further provide the technical details of a related system which optimizes and comprehensively automates microfluidic blood assays such that even non-technical users who have never worked with microfluidics can regularly obtain the same standard of data that is produced in the lab.</p
Atmospheric Reactive Trace Gas Observations in Field and Chamber Studies Using CF₃O⁻ Chemical Ionization Mass Spectrometry
Get PDFThis dissertation describes the development of chemical ionization mass spectrometry (CIMS) instrumentation and methods utilizing the CF3O- reagent ion for the sensitive, specific, and direct detection of many oxygenated volatile organic compounds (OVOC) and inorganic reactive trace gases in the atmosphere. These species include HNO3, HONO, HO2NO2, SO2, HCN, H2O2, CH3OOH, CH3(O)OOH, HC(O)OH, CH3C(O)OH, HC(O)CH2OH, CH3C(O)CH2OH, organic hydroperoxides (ROOH), and many additional multifunctional species (e.g., hydroxynitrates, hydroxycarbonyls, hydroxyhydroperoxides, carbonylnitrates, carbonylhydroperoxides, etc.).
CF3O--tandem mass spectrometry (MSMS) is demonstrated to be useful for distinguishing and individual quantification of certain isobaric compounds, as well as solving instrumental background problems for certain species. This technology is applied in field studies conducted from aircraft and ground-based platforms and to chamber studies investigating VOC oxidation and organic aerosol formation mechanisms. Comparisons with simultaneous observations from other instrumentation for several species show good agreement with CIMS observations. CF3O--CIMS observations of HCN (a biomass burning tracer) from aircraft are used to quantify the impact of biomass burning emissions to the Mexico City region in March 2006. Biomass burning emissions are shown to contribute significantly to a number of gas and aerosol phase pollutants even in the midst of the large anthropogenic pollution emissions from Mexico City. The analysis of the photochemical aging of a fire plume over the Yucatan Peninsula (March 2006) is also reported. Observations indicate intense chemistry occurring within the fire plume evidenced by high OH levels, fast production of H2O2 and conversion of NO and NO2 (NOx) into peroxyacetylnitrate (PAN) and aerosol nitrate. This rapid chemistry is likely driven by photolysis of HONO, which is observed to be emitted in high amounts from these fires.
The CIMS methods are applied to studies of VOC oxidation and organic aerosol formation conducted in chamber experiments. Specifically, new insights gained from the study of isoprene oxidation under high and low NOx conditions are reported. We quantify the formation of small carboxylic acids as well as C5-hydroxynitrates from the oxidation of isoprene under high NOx conditions. Under low NOx conditions, we show that C5-hydroxyhydroperoxides are formed in high yield. Subsequent oxidation of these hydroxyhydroperoxides is shown to occur through a unique HOx neutral mechanism that generates C5-epoxydiols, a likely precursor to organic aerosol.
We utilize the high sensitivity and specificity of CF3O- -CIMS to study novel intermolecular hydrogen-shift isomerization processes in peroxy radicals formed during isoprene oxidation. We find these rates to be substantially slower than recent theoretical predictions; however, we find these isomerization rates to be fast enough that they are important in atmospheric isoprene oxidation in regions where lifetimes become long. Globally, we estimate 8-11% of isoprene peroxy radicals react through 1,6-H-shift isomerization reactions.</p
New Tools for Studying O-G1cNAc Glycosylation and Chondroitin Sulfate Proteoglycans and Studies on the Roles of O-G1cNAc Glycosylation on the Transcription Factor CREB
Get PDFThe addition and removal of the monosaccharide N-acetyl-D-glucosamine (GlcNAc) to serine and threonine residues of proteins has emerged as a critical regulator of cellular processes. However, studies of O-GlcNAc in such complex systems as the brain have been limited, in part due to the lack of tools. Here we report the development of new tools for studying O-GlcNAc, and the application of these and other tools for studying the roles of O-GlcNAc in the brain.
Working from a previously established chemoenzymatic method, we designed an isotopic labeling strategy for probing the dynamics of O-GlcNAc glycosylation using quantitative proteomics. With this tool, we show that O-GlcNAc is dynamically modulated on specific proteins by excitatory stimulation of the brain in vivo. Separately, we improved this chemoenzymatic strategy by integrating [3+2] azide-alkyne cycloaddition chemistry to attach biotin and fluorescent tags to O-GlcNAc residues. These tags allow for the direct fluorescence detection, proteomic analysis, and cellular imaging of O-GlcNAc modified proteins. With this strategy, we identified over 146 novel glycoproteins from the mammalian brain.
The transcription factor cAMP-response element binding protein (CREB) is critical for numerous functions in the brain, including neuronal survival, neuronal development, synaptic plasticity, and long-term memory. We show that CREB is highly glycosylated in the brain and discover new glycosylation sites on CREB in neurons. One of these sites is dynamically modulated and is important for regulating CREB. Removal of this glycosylation site alters CREB-mediated functions in vitro and in vivo. These studies are the first demonstration that O-glycosylation at a specific site on a specific protein is critical for neuronal function and behavior.
Chondroitin sulfates (CS) are sulfated linear polysaccharides important in neuronal development and viral invasion. Depending on their sulfation patterns, CS molecules differ dramatically in their functions. We developed a computational method to model the structure and function of CS. Using this approach, we show that different CS tetrasaccharides have distinct solution structures. We also modeled the CS binding site on a variety of proteins and discovered that CS may be important in modulating protein-protein interactions.</p
Palladium(II)-Catalyzed Oxidation Reactions in Natural Product Synthesis: Efforts toward Bielschowskysin and Phalarine
Get PDFTwo types of oxidative transformations, an oxidative kinetic resolution and an oxidative heterocyclization, have been developed by several laboratories using palladium(II)-catalysis to provide enantioenriched products. The main drawback of these asymmetric transformations is the limited substrate scope for each set of conditions. To address this, the Stoltz laboratory developed a unique platform utilizing palladium(II)-catalysis that provides a highly effective oxidative kinetic resolution of secondary alcohols and an asymmetric oxidative heterocyclization of phenols. Key to this platform is the use of (–)-sparteine as the chiral ligand and O2 as the stoichiometric oxidant. Both of these methodologies will be featured in this thesis as they were applied toward the total synthesis of complex natural products.
Our palladium(II)-catalyzed oxidative kinetic resolution was used to access an enantioenriched intermediate in our efforts toward the synthesis of bielschowskysin, a polycyclic diterpenoid. A key disconnection in our strategy was formation of the cyclobutane core of bielschowskysin from a cyclopropane intermediate. After considerable experimentation, we were able to synthesize a cyclopropane intermediate that could be used for future research.
In separate work, we hoped to use two palladium(II)-catalyzed oxidative heterocyclization reactions to provide the core of phalarine, a polycyclic alkaloid. The synthesis of a key intermediate relied on a Stille coupling reaction of a complex 4,5,7-substituted indole and a nitro-arene. Model cyclization studies on an aniline substrate gave inconclusive results, while a model of a phenolic substrate has shown that cyclization onto styrenyl olefins is possible.</p