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Testing Inflationary Cosmology with the BICEP1 and BICEP2 Experiments
Get PDFRecent observations of the temperature anisotropies of the cosmic microwave background (CMB) favor an inflationary paradigm in which the scale factor of the universe inflated by many orders of magnitude at some very early time. Such a scenario would produce the observed large-scale isotropy and homogeneity of the universe, as well as the scale-invariant perturbations responsible for the observed (10 parts per million) anisotropies in the CMB. An inflationary epoch is also theorized to produce a background of gravitational waves (or tensor perturbations), the effects of which can be observed in the polarization of the CMB. The E-mode (or parity even) polarization of the CMB, which is produced by scalar perturbations, has now been measured with high significance. Con- trastingly, today the B-mode (or parity odd) polarization, which is sourced by tensor perturbations, has yet to be observed. A detection of the B-mode polarization of the CMB would provide strong evidence for an inflationary epoch early in the universe’s history.
In this work, we explore experimental techniques and analysis methods used to probe the B- mode polarization of the CMB. These experimental techniques have been used to build the Bicep2 telescope, which was deployed to the South Pole in 2009. After three years of observations, Bicep2 has acquired one of the deepest observations of the degree-scale polarization of the CMB to date. Similarly, this work describes analysis methods developed for the Bicep1 three-year data analysis, which includes the full data set acquired by Bicep1. This analysis has produced the tightest constraint on the B-mode polarization of the CMB to date, corresponding to a tensor-to-scalar ratio estimate of r = 0.04±0.32, or a Bayesian 95% credible interval of r < 0.70. These analysis methods, in addition to producing this new constraint, are directly applicable to future analyses of Bicep2 data. Taken together, the experimental techniques and analysis methods described herein promise to open a new observational window into the inflationary epoch and the initial conditions of our universe.</p
Grain Growth in Protoplanetary Disks
Get PDFThe majority of young, low-mass stars are surrounded by optically thick accretion disks. These circumstellar disks provide large reservoirs of gas and dust that will eventually be transformed into planetary systems. Theory and observations suggest that the earliest stage toward planet formation in a protoplanetary disk is the growth of particles, from sub-micron-sized grains to centimeter- sized pebbles. Theory indicates that small interstellar grains are well coupled into the gas and are incorporated to the disk during the proto-stellar collapse. These dust particles settle toward the disk mid-plane and simultaneously grow through collisional coagulation in a very short timescale. Observationally, grain growth can be inferred by measuring the spectral energy distribution at long wavelengths, which traces the continuum dust emission spectrum and hence the dust opacity. Several observational studies have indicated that the dust component in protoplanetary disks has evolved as compared to interstellar medium dust particles, suggesting at least 4 orders of magnitude in particle- size growth. However, the limited angular resolution and poor sensitivity of previous observations has not allowed for further exploration of this astrophysical process.
As part of my thesis, I embarked in an observational program to search for evidence of radial variations in the dust properties across a protoplanetary disk, which may be indicative of grain growth. By making use of high angular resolution observations obtained with CARMA, VLA, and SMA, I searched for radial variations in the dust opacity inside protoplanetary disks. These observations span more than an order of magnitude in wavelength (from sub-millimeter to centimeter wavelengths) and attain spatial resolutions down to 20 AU. I characterized the radial distribution of the circumstellar material and constrained radial variations of the dust opacity spectral index, which may originate from particle growth in these circumstellar disks. Furthermore, I compared these observational constraints with simple physical models of grain evolution that include collisional coagulation, fragmentation, and the interaction of these grains with the gaseous disk (the radial drift problem). For the parameters explored, these observational constraints are in agreement with a population of grains limited in size by radial drift. Finally, I also discuss future endeavors with forthcoming ALMA observations.</p
Design of Nanoparticles that Cross the Blood-Brain Barrier by Receptor Mediated Transcytosis
Get PDFThe primary objective of my thesis work is to establish a set of design criteria for nanoparticles whose purpose is to safely and efficiently access the brain after systemic injection. Nanoparticles that can access the brain may be able to deliver therapeutic molecules to the brain that otherwise would be excluded by the blood-brain barrier.
E. coli glycoprotein 96 (Ecgp96) is explored as a candidate receptor on the blood-brain barrier that could potentially facilitate nanoparticle-receptor mediated transcytosis into the brain. Results from studies utilizing PET/CT, SPECT/CT, MRI, Xenogen fluorescence imaging, and confocal microscopy conclude that Ecgp96 is observed in the blood-brain barrier endothelial cells, but is not accessible from the blood of adult or neonatal mice under normal, non-pathological conditions.
Transferrin receptor is a well-characterized receptor on the blood-brain barrier that is accessible from the blood and known to transcytose transferrin. I focused on this receptor and on synthesizing and characterizing a well-defined set of transferrin containing gold nanoparticles of various sizes and transferrin compositions that would be investigated during in-vivo studies. Nanoparticle sizes were measured by DLS and nanoparticle tracking analysis. Zeta potentials were also measured. Nanoparticle transferrin content was directly measured by labeling transferrin with 64Cu and measuring the nanoparticle associated gamma activity. The nanoparticle binding avidities to mouse transferrin receptors were ranked by a silver enhancement fluorescence-based method using the mouse Neruo2A cell line.
Each nanoparticle formulation was systemically injected into mice, and localization in the mouse brain was observed by silver enhancement light microscopy, and TEM. The quantitation of the gold was determined by ICP-MS. Nanoparticles with large amounts of transferrin remain strongly attached to brain endothelial cells, while nanoparticles with less transferrin are capable of both interacting with transferrin receptor on the luminal side of the blood-brain barrier and detaching from transferrin receptor on the brain side of the blood-brain barrier. These results highlight the fact that the nanoparticle avidity must be tuned to maximize the number of nanoparticles exiting the endothelial cells and entering the brain tissue. Lanthanum nitrate perfusion-fixation studies demonstrate that the nanoparticle formulations investigated do not degrade the blood-brain barrier integrity and enter the brain by transferrin receptor-mediated transcytosis. The results from these studies provide initial design criteria for creating nanoparticle therapeutics for delivery to the brain from systemic administrations.</p
Four Essays on the Empirical Analysis of Political Ideology
Get PDFThis thesis examines four distinct facets and methods for understanding political ideology, and so it includes four distinct chapters with only moderate connections between them. Chapter 2 examines how reactions to emotional stimuli vary with political opinion, and how the stimuli can produce changes in an individuals political preferences. Chapter 3 examines the connection between self-reported fear and item nonresponse on surveys. Chapter 4 examines the connection between political and moral consistency with low-dimensional ideology, and Chapter 5 develops a technique for estimating ideal points and salience in a low-dimensional ideological space
The Relationship Between the Radio and Gamma-Ray Emission of Blazars
Get PDFBlazars are active galaxies with a jet closely oriented to our line of sight. They are powerful, variable emitters from radio to gamma-ray wavelengths. Although the general picture of synchrotron emission at low energies and inverse Compton at high energies is well established, important aspects of blazars are not well understood. In particular, the location of the gamma-ray emission region is not clearly established, with some theories favoring a location close to the central engine, while others place it at parsec scales in the radio jet.
We developed a program to locate the gamma-ray emission site in blazars, through the study of correlated variations between their gamma-ray and radio-wave emission. Correlated variations are expected when there is a relation between emission processes at both bands, while delays tell us about the relative location of their energy generation zones. Monitoring at 15 GHz using the Owens Valley Radio Observatory 40 meter telescope started in mid-2007. The program monitors 1593 blazars twice per week, including all blazars detected by the Fermi Gamma-ray Space Telescope (Fermi) north of -20 degrees declination. This program complements the continuous monitoring of gamma-rays by Fermi.
Three year long gamma-ray light curves for bright Fermi blazars are cross-correlated with four years of radio monitoring. The significance of cross-correlation peaks is investigated using simulations that account for the uneven sampling and noise properties of the light curves, which are modeled as red-noise processes with a simple power-law power spectral density. We found that out of 86 sources with high quality data, only three show significant correlations (AO 0235+164, B2 2308+34 and PKS 1502+106). Additionally, we find a significant correlation for Mrk 421 when including the strong gamma-ray/radio flare of late 2012. In all four cases radio variations lag gamma-ray variations, suggesting that the gamma-ray emission originates upstream of the radio emission. For PKS 1502+106 we locate the gamma-ray emission site parsecs away from the central engine, thus disfavoring the model of Blandford and Levinson (1995), while other cases are inconclusive. These findings show that continuous monitoring over long time periods is required to understand the cross-correlation between gamma-ray and radio-wave variability in most blazars.</p
Structure-Function Studies of Nicotinic Acetylcholine Receptors Using Unnatural Amino Acids and Synthetic Agonist Analogs
Get PDFThis dissertation primarily describes structure-function studies of the prototypical Cys-loop ligand-gated ion channel, the nicotinic acetylcholine receptors (nAChRs).
Agonists that bind nAChRs, including acetylcholine, nicotine, and the smoking cessation drug varenicline, share one of the longest-known, best-studied pharmacophores, consisting of a cationic N and a hydrogen bond acceptor. A major theme of this thesis is concerned with defining the nAChR residues that bind the nicotinic pharmacophore. Chapters 2 and 3 establish that a hydrogen bond links the pharmacophore’s hydrogen bond acceptor to a backbone NH in the protein. The establishment of this interaction, and the disproval of other predicted interactions, represents the completion of the nicotinic pharmacophore binding model. Chapter 4 uses this model to characterize how the nAChR differentiates between stereoisomers of an agonist.
Chapter 5 describes functional studies of a vicinal disulfide that has played a pivotal role in a number of pioneering studies of nAChRs. Despite its historical importance, the functional role of this disulfide has not been defined. We identify a speculative role for the vicinal disulfide that involves the formation of a functionally important network of hydrogen bonds.
Chapter 6 outlines three strategies for the photochemical cleavage of protein and peptide backbones using unnatural amino acids. One of these strategies is based on a selenide-mediated cleavage of a backbone ester moiety. Model studies establish the viability of this chemistry and suggest that it could be a useful tool for protein structure-function studies.
Chapter 7 concerns preliminary work from a collaboration with laboratories from USC and Caltech that is aimed at developing small-molecule treatments for vision loss associated with photoreceptor degeneration. The initial goal of this project is to develop a photosensitive small molecule that can activate a voltage-gated potassium channel.
The final chapter discusses work that was done in the Grubbs lab at Caltech in which a strategy for preparing N-heterocyclic carbene-containing metal complexes was developed.</p
Investigations on Low-Valent Group 8 and 9 Metalloradicals
Get PDFTetradentate, monoanionic, tris(phosphino)silyl ligands were chelated to group 8 and 9 transition metals to stabilize complexes with unusual oxidation states and/or geometries. Initial studies with the [SiPPh3]− ligand on ruthenium established the flexibility of this ancillary ligand in stabilizing complexes with strongly trans influencing ligands in trans dispositions. A related ligand scaffold, [SiPiPr3]−, was subsequently used to stabilize mononuclear complexes of Ru(I) and Os(I), the first examples to be isolated and thoroughly chracterized. EPR spectroscopy and DFT calculations supported their metalloradical character, and further studies highlighted their reactivity in both one- and two-electron redox processes. The ability of the [SiPiPr3]− scaffold to stabilize d7 metalloradicals of group 8 metals was extended to group 9 metals, and a series of d7 complexes of cobalt, rhodium, and iridium were synthesized in which their ancillary ligands, oxidation states, spin states, and geometry are conserved. Similar to the previously reported [SiPiPr3]Fe(N2) complex, the related [SiPiPr3]Ru(N2) complex was shown to exhibit N−N coupling of organic azides to yield azoarenes catalytically. Detailed mechanistic studies conclusively showed that the Ru(III) imide species, whose iron analog is the key intermediate in the [SiPiPr3]Fe system, is not involved in the mechanism for the [SiPiPr3]Ru system. Instead, a mechanism in which free nitrene is released during the catalytic cyle is favored. Finally, hybrid ligands with multiple thioether donors in place of phosphine donors on the [SiPR3]− scaffold were synthesized to stabilize a number of dinitrogen complex of iron. These complexes featured rare examples of S−Fe−N2 linkages
Zebrafish Magnetite and Long-lived Rohon-Beard Neurons: Expanding Our View of Two Zebrafish Sensory Systems in Development and Adulthood
Get PDFDuring embryogenesis, the central nervous system (CNS) transforms from what seems like an amorphous mass of cells to a rod-like structure, and then to a fully functional and complex system of tissues composed of multiple cell types. Using confocal laser scanning microscopy (CLSM), I demonstrate a modified version of in toto imaging to track normal spinal cord organization in zebrafish from bud stage, ~ 11 hours post-fertilization (hpf), to 48 hpf. I also assisted in identifying several transgenic lines using a gene trap vector, the FlipTrap (FT), which creates a normally localized and functional fluorescent fusion protein for in vivo analysis of gene expression throughout development. I used two FT lines along with a modified version of in toto imaging to study sensory cells in the dorsal spinal cord.
With the FT tool, I discovered a subset of Rohon-Beard (RB) neurons that perdures into the adult. These uniquely transient chemo- and mechano-sensory cells have been well characterized in the dorsal spinal cord of lower vertebrates; however, the notion of persistent RBs contrasts with dogma suggesting that the entire population disappears during the early larval period. The coexistence of RB-like neurons with dorsal root ganglia (DRG) suggests that zebrafish have two post-embryonic sensory systems, challenging the previous notion that only peripheral sensory neurons survive.
In the second part of my dissertation I describe my studies of biogenic magnetite which has been detected in a broad range of organisms, including magnetotactic bacteria, migratory fish and birds, invertebrates, and humans. Magnetite mediates magnetosensation in many species through the effects of pulse-remagnetization on behavior. The mechanisms of magnetite biomineralization are not well characterized in higher organisms. Previous studies have shown deposits of magnetite in projections of the trigeminal nerve, alongside behavioral evidence suggesting that both optical pumping and magnetite-based mechanisms may operate simultaneously. Subsequent efforts to identify the anatomical seat of magnetoreceptors have focused on the same locations in new organisms, excluding other areas. Here I report the unexpected presence of biogenic magnetite in the lateral line region of the genetically and physiologically tractable vertebrate model organism, Danio rerio.</p
Microstructural, Metamorphic and Experimental Constraints on Differential Stress and Temperature in the Middle Crust
Get PDFBecause shear stress drives plate tectonics and causes earthquakes, important objectives in the Earth Sciences include quantifying stress magnitudes and variability in space and time, and developing and improving tools to do so. This thesis addresses both objectives. In the first chapter I demonstrate that the Titanium-in-quartz thermobarometer ("TitaniQ") can be used to accurately record deformation temperatures under greenschist facies conditions. In the second chapter, an experimental study, I show that the relationship between recrystallized grain size and flow stress (the “recrystallized grain size paleopiezometer”) can be used to determine the stress history of dynamically recrystallized quartz under non steady state conditions. In the third chapter I apply the paleopiezometer in Taiwan’s Hsüehshan range and compare results to independent constraints (e.g. critical taper theory and potential energy considerations). This analysis demonstrates: 1) the piezometer is accurate to within a factor of two or better under conditions at the brittle-ductile transition; 2) piezometric results are consistent with recent flow laws for quartz; 3) the activation energy of naturally deformed quartzite is >133 kJ/mol, consistent with experimental determinations; and 4) Peak differential stress in the Hsüehshan range was ~210 MPa at temperature ~300°C. Our results indicate hydrostatic fluid pressure and a low friction coefficient of ~0.38 within the Taiwan wedge. Integrated crustal strength in Taiwan is 1.5-2.1*1012 N/m, consistent with the force needed to support the topography of the range. The final chapter investigates stress levels on the Vincent thrust in the San Gabriel Mountains, California by constructing a numerical model of the initiation of flat slab subduction. A model inversion demonstrates that previously hypothesized high stresses are not required to explain inverted metamorphism along the fault
Nanostructured Silicon Thermoelectrics
Get PDFThe thesis discusses the thermoelectric properties of silicon nanostructures with a particular focus on their heat transport phenomenon. The aim of this thesis work is to design ultra-low thermal conductivity materials based on fundamental phonon physics. Silicon nanowires and silicon nanomeshes are the model nanostructure systems investigated in this thesis.
Degenerately boron-doped silicon nanowires (20 nm x 20 nm cross section) exhibit thermal conductivity, depending on the temperature of interest, roughly two orders of magnitude smaller than bulk silicon with similar impurity concentration. The reduction in thermal conductivity is presumably from increased boundary scattering of the thermal phonons. For smaller nanowire systems (e.g., 10 nm x 20 nm cross section), thermal conductivity lower than the amorphous limit is also observed. Dimensional crossover of the thermal phonons in these ultra-small nanowire systems is proposed to explain the thermal conductivity reduction. Thermoelectric figure-of-merit ZT~1, a two order of magnitude improvement is achieved in 20 nm x 20 nm silicon nanowires at 200K.
Silicon nanomeshes are designed to further reduce the thermal conductivity of silicon. The 2-D hole-array is patterned on the silicon nanomesh film as Bragg reflectors to slow down the phonon group velocity. From the direct thermal conductivity measurement via suspended microstructure platform, the coherent scattering mechanism effectively reduces the thermal conductivity of silicon by a factor of two from the nanowire value. In essence, the phononic metamaterial approach essentially creates a new class of silicon-based material with distinct phonon properties, in other words, the theoretical lower limit of thermal conductivity of silicon based on bulk dispersions no longer applies to the phononic nanomeshes. In addition, silicon nanomeshes exhibit bulk-like electrical conductivity rendering them potential high efficiency thermoelectrics.
In Chapter 1, an introduction to the lattice thermal conductivity is given to point out the key parameters affecting the phonon transport, e.g., scattering mechanisms, phonon dispersions and phonon density-of-states. The thermoelectrics fundamentals are given in Chapter 2, as are the experimental results on silicon nanowires. The fabrication and measurement methodologies are also explained in this chapter. In Chapter 3, the phonon transport mechanism of the silicon nanomesh, a new class of phononic metamaterial, is investigated. A coherent phonon scattering mechanism is used to explain the unexpected phonon behaviors. A complete fabrication process flow is also developed in this chapter in order to fully release the nanostructure from the substrate for precise and accurate thermal conductivity measurement. In the last part of the thesis (Chapter 4), the phononic nanomesh approach is extended to a nanomesh superlattice structure. The architectural design is to incorporate interfacial thermal resistance or the Kapitza resistance to further reduce the thermal conductivity of silicon. In addition, device architecture consisting of self-assembled quantum dots is proposed to enhance the thermoelectric efficiency by energy-filtering mechanism.</p