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Technology Advances for Radio Astronomy
Get PDFThe field of radio astronomy continues to provide fundamental contributions to the understanding of the evolution, and inner workings of, our universe. It has done so from its humble beginnings, where single antennas and receivers were used for observation, to today's focal plane arrays and interferometers. The number of receiving elements (pixels) in these instruments is quickly growing, currently approaching one hundred. For the instruments of tomorrow, the number of receiving elements will be in the thousands. Such instruments will enable researchers to peer deeper into the fabric of our universe and do so at faster survey speeds. They will provide enormous capability, both for unraveling today's mysteries as well as for the discovery of new phenomena.
Among other challenges, producing the large numbers of low-noise amplifiers required for these instruments will be no easy task. The work described in this thesis advances the state of the art in three critical areas, technological advancements necessary for the future design and manufacturing of thousands of low-noise amplifiers. These areas being: the automated, cryogenic, probing of \diameter100 mm indium phosphide wafers; a system for measuring the noise parameters of devices at cryogenic temperatures; and the development of low-noise, silicon germanium amplifiers for terahertz mixer receivers. The four chapters that comprise the body of this work detail the background, design, assembly, and testing involved in these contributions. Also included is a brief survey of noise parameters, the knowledge of which is fundamental to the design of low-noise amplifiers and the optimization of the system noise temperature for large, dense, interferometers.</p
Conceptual Framework and Physical Implementation of a Systematic Design Strategy for Tissue-Engineered Devices
Get PDFTissue-engineered and biologically inspired devices promise to advance medical implants, robotic devices and diagnostic tools. Ideally, biohybrid constructs combine the versatility and fine control of traditional building substrates with dynamic properties of living tissues including sensory modalities and mechanisms of repair, plasticity and self-organization. These dynamic properties also complicate the design process as they arise from, and act upon, structure-function relationships across multiple spatiotemporal scales that need to be recapitulated in the engineered tissue. Biomimetic designs merely copying the structure of native organs and organisms, however, are likely to reflect evolutionary constraints, phenotypic variability and environmental factors rather than rendering optimal engineering solutions.
This thesis describes an alternative to biomimetic design, i.e., a systematic approach to tissue engineering based on mechanistic analysis and a focus on functional, not structural, approximation of native and engineered system. As proof of concept, the design, fabrication and evaluation of a tissue-engineered jellyfish medusa with biomimetic propulsion and feeding currents is presented with an emphasis on reasoning and strategy of the iterative design process. A range of experimental and modeling approaches accomplishes mechanistic analysis at multiple scales, control of individual and emergent cell behavior, and quantitative testing of functional performance. The main achievement of this thesis lies in presenting both conceptual framework and physical implementation of a systematic design strategy for muscular pumps and other bioinspired and tissue-engineered applications.</p
On the Analysis and Design of the Locust Olfactory System
Get PDFThe ~ 830 projection neurons (PNs) of the locust antennal lobe respond to odors with dense, odor-specific spatio-temporal activity patterns that are mapped via intrinsic and circuit properties into a sparse representation by the Kenyon cells of the mushroom body, which are in turn read out by the beta-lobe neurons (bLNs). In this thesis we present several analyses of this system. First, we describe metrics for quantifying the geometric properties of PN population responses in the full response space that verify the structures revealed by locally linear embedding. Second, we analyze the mixture responses of single PNs and find that in many cases the mixture response can be explained using one of the component responses. Grouping PNs by their single component preferences reveals a potentially simple substrate for olfactory computations. Third, we look for evidence of cycle-by-cycle decoding of PNs by KCs. We show that much of the variance in single KC responses can be explained using small numbers of PNs, and conversely, that PN odor response trajectories can be reconstructed using KC responses. Finally, in a theoretical / computational analysis, we assemble some of the basic biological facts about the locust olfactory system into an architecture for the online learning of arbitrary mappings from odors to valences
Stochastic Simulation of the Kinetics of Multiple Interacting Nucleic Acid Strands
Get PDFDNA nanotechnology is an emerging field which utilizes the unique structural properties of nucleic acids in order to build nanoscale devices, such as logic gates, motors, walkers, and algorithmic structures. Predicting the structure and interactions of a DNA device requires good modeling of both the thermodynamics and the kinetics of the DNA strands within the system. The kinetics of a set of DNA strands can be modeled as a continuous time Markov process through the state space of all secondary structures. The primary means of exploring the kinetics of a DNA system is by simulating trajectories through the state space and aggregating data over many such trajectories.
We expand on previous work by extending the thermodynamics and kinetics models to handle multiple strands in a fixed volume, and show that the new models are consistent with previous models. We developed data structures and algorithms that allow us to take advantage of local properties of secondary structure, improving the efficiency of the simulator so that we can handle larger systems. The new kinetic parameters in our model were calibrated by analyzing simulator results on experimental systems that measure basic kinetic rates of various processes. Finally, we apply the new simulator to explore a case study on toehold-mediated four-way branch migration.</p
Expanding Protein Sequence Space through Incorporation of Non-Canonical Amino Acids
Get PDFProtein sequence space has been augmented by researchers wanting to expand the diversity of chemical functionalities that can exist within proteins. Artificial amino acids can range from simple atom substitutions such as fluorination, to installation of reactive handles like azides and alkynes. Researchers build upon the framework of natural proteins and have developed methods of installing a wide variety of artificial amino acids into proteins. Chapter 1 discusses in detail the two methods for metabolic incorporation of unnatural amino acids: site-specific incorporation and residue-specific incorporation. Advantages and disadvantages to each method are detailed as well as applications of these methods to the examination of problems in chemical biology.
Non-canonical amino acids analogues that are structurally similar to their canonical counterparts can be recognized by the endogenous translational machinery for residue-specific incorporation. Chapter 2 describes the directed evolution of the methionyl-tRNA synthetase (MetRS) to incorporate propargylglycine, an alkyne analogue that is not recognized by the wild-type MetRS. A new MetRS variant active towards propargylglycine was identified after screening libraries of both active site mutations and error-prone PCR mutations. PraRS is capable of producing proteins where methionine is quantitatively replaced by propargylglycine. PraRS also does not recognize azidonorleucine, an azide methionine analogue for which the NLL-MetRS was evolved in order to enable cell-specific protein labeling. A method to identify cellular origins of proteins from two different bacterial strains in co-culture was developed using the NLL-MetRS and PraRS.
hapter 3 illustrates the effects of global incorporation of non-canonical amino acids into globular proteins. Although trifluoroleucine and homoisoleucine have shown to increase the thermostability of model proteins, incorporation into more chloramphenicol acetyltransferase (CAT) does not yield the same benefits. We find that mutations that stabilize CAT for fluorinated amino acid incorporation do not protect against homoisoleucine incorporation.
Lastly, access to new chemical reactions for protein modification requires synthesis and incorporation of new non-canonical amino acid analogues. Chapter 4 describes the design of two new artificial amino acids, S-allyl-homocysteine and 3-furanylalanine, for residue specific incorporation without expression of mutant synthetases. Also, a third amino acid, azidomethylphenylalanine, was designed for activation by a previously discovered phenylalanine-tRNA synthetase mutant. Incorporation of these three analogues provides chemical handles that are potential reagents for cross metathesis, Diels-Alder cycloaddition, and generation of a molecular epitope for binding to synthetic receptors. </p
Synthetic Applications and Methodological Developments of Donor-Acceptor Cyclopropanes
Get PDFDonor–acceptor cyclopropanes are a versatile class of synthetic intermediates, compatible in a broad range of ring-opening reactions and formal cycloadditions, and employed in numerous natural product syntheses. We have developed new Lewis acid mediated cycloadditions for the synthesis of five-membered heterocycles, and applied existing a transition metal catalyzed cyclopropane cycloaddition method toward the synthesis of complex alkaloids.
First, described is the development of a Lewis acid mediated (3 + 2) cycloaddition of donor–acceptor cyclopropanes with isocyanates, isothiocyanates and carbodiimides. This reaction was found in certain cases to proceed with excellent stereochemical fidelity, providing access to an array of enantioenriched thioimidates and amidines.
Second, we targeted the Melodinus alkaloids for total synthesis due to their unique structural features. Synthetic efforts toward scandine, the parent of the natural product family, are detailed herein. Our approach features a palladium catalyzed formal (3 + 2) cycloaddition of a vinyl cyclopropane and a β-nitrostyrene to rapidly assemble the central cyclopentane core of the natural product. Initial efforts focused on the synthesis and application of a 1,1-divinylcyclopropane to the formal (3 + 2) cycloaddition reaction, whereas later work entailed the use of a mono-vinylcyclopropane with the goal of installing the second requisite vinyl group at a later stage using modern C–H functionalization technologies.</p
Essays on Contests, Coordination Games, and Matching
Get PDFIn this thesis, I use theory and experiments (sometimes only experiments), to investigate the impact of agents’ heterogeneity on economic environments such as tournaments, decentralized matching, and coordination games.
The first chapter analyzes a coordination game (a stag-hunt game) in which one of the equilibria gives a higher payoff to the players, but playing the corresponding strategy profile leading to this equilibrium entails strategic risk. In this chapter, I ask whether agents can coordinate on the equilibrium that gives a higher payoff when they are provided information about an opponent’s risk aversion. Two key insights result from my analysis. First, a subject’s propensity to choose the risky action depends on her opponent’s risk attitude. Second, this propensity is independent of the subject’s own risk attitude.
The second chapter compares the performance of two tournament designs when contestants are heterogeneous in their abilities. One of the designs is the standard winner-take-all (WTA) tournament, which is common both in the literature and in the real world. The alternative tournament design involves two tournaments with different prizes (parallel tournaments) where individuals choose which tournament to enter before competing. With a simple model and an experiment, I show that when contestants’ abilities differ substantially, the designer makes higher profit using parallel tournaments. Nevertheless, when the contestants’ abilities are similar, the designer makes higher profit in the WTA tournament.
The third chapter studies a two-period decentralized matching game under complete information with frictions in the form of time discounting. I find that the sub-game perfect Nash equilibrium outcome of this game coincides with a stable outcome for most preference profiles. The selection of which stable outcome emerges depends on the level of frictions: the sub-game perfect Nash equilibrium outcome of this game yields the firm-optimal stable match (a worker-optimal stable match) when the time discount is sufficiently high or low (intermediate values).</p
Deviation from Standard Inflationary Cosmology and the Problems in Ekpyrosis
Get PDFThere are two competing models of our universe right now. One is Big Bang with inflation cosmology. The other is the cyclic model with ekpyrotic phase in each cycle. This paper is divided into two main parts according to these two models. In the first part, we quantify the potentially observable effects of a small violation of translational invariance during inflation, as characterized by the presence of a preferred point, line, or plane. We explore the imprint such a violation would leave on the cosmic microwave background anisotropy, and provide explicit formulas for the expected amplitudes ⟨almal'm'*⟩ of the spherical-harmonic coefficients. We then provide a model and study the two-point correlation of a massless scalar (the inflaton) when the stress tensor contains the energy density from an infinitely long straight cosmic string in addition to a cosmological constant. Finally, we discuss if inflation can reconcile with the Liouville's theorem as far as the fine-tuning problem is concerned. In the second part, we find several problems in the cyclic/ekpyrotic cosmology. First of all, quantum to classical transition would not happen during an ekpyrotic phase even for superhorizon modes, and therefore the fluctuations cannot be interpreted as classical. This implies the prediction of scale-free power spectrum in ekpyrotic/cyclic universe model requires more inspection. Secondly, we find that the usual mechanism to solve fine-tuning problems is not compatible with eternal universe which contains infinitely many cycles in both direction of time. Therefore, all fine-tuning problems including the flatness problem still asks for an explanation in any generic cyclic models
Detailed Properties of High Redshift Galaxies
Get PDFGalaxies evolve throughout the history of the universe from the first star-forming sources, through gas-rich asymmetric structures with rapid star formation rates, to the massive symmetrical stellar systems observed at the present day. Determining the physical processes which drive galaxy formation and evolution is one of the most important questions in observational astrophysics. This thesis presents four projects aimed at improving our understanding of galaxy evolution from detailed measurements of star forming galaxies at high redshift.
We use resolved spectroscopy of gravitationally lensed z ≃ 2 - 3 star forming galaxies to measure their kinematic and star formation properties. The combination of lensing with adaptive optics yields physical resolution of ≃ 100 pc, sufficient to resolve giant Hii regions. We find that ~ 70 % of galaxies in our sample display ordered rotation with high local velocity dispersion indicating turbulent thick disks. The rotating galaxies are gravitationally unstable and are expected to fragment into giant clumps. The size and dynamical mass of giant Hii regions are in agreement with predictions for such clumps indicating that gravitational instability drives the rapid star formation. The remainder of our sample is comprised of ongoing major mergers. Merging galaxies display similar star formation rate, morphology, and local velocity dispersion as isolated sources, but their velocity fields are more chaotic with no coherent rotation.
We measure resolved metallicity in four lensed galaxies at z = 2.0 − 2.4 from optical emission line diagnostics. Three rotating galaxies display radial gradients with higher metallicity at smaller radii, while the fourth is undergoing a merger and has an inverted gradient with lower metallicity at the center. Strong gradients in the rotating galaxies indicate that they are growing inside-out with star formation fueled by accretion of metal-poor gas at large radii. By comparing measured gradients with an appropriate comparison sample at z = 0, we demonstrate that metallicity gradients in isolated galaxies must flatten at later times. The amount of size growth inferred by the gradients is in rough agreement with direct measurements of massive galaxies. We develop a chemical evolution model to interpret these data and conclude that metallicity gradients are established by a gradient in the outflow mass loading factor, combined with radial inflow of metal-enriched gas.
We present the first rest-frame optical spectroscopic survey of a large sample of low-luminosity galaxies at high redshift (L < L*, 1.5 < z < 3.5). This population dominates the star formation density of the universe at high redshifts, yet such galaxies are normally too faint to be studied spectroscopically. We take advantage of strong gravitational lensing magnification to compile observations for a sample of 29 galaxies using modest integration times with the Keck and Palomar telescopes. Balmer emission lines confirm that the sample has a median SFR ∼ 10 M_sun yr^−1 and extends to lower SFR than has been probed by other surveys at similar redshift. We derive the metallicity, dust extinction, SFR, ionization parameter, and dynamical mass from the spectroscopic data, providing the first accurate characterization of the star-forming environment in low-luminosity galaxies at high redshift. For the first time, we directly test the proposal that the relation between galaxy stellar mass, star formation rate, and gas phase metallicity does not evolve. We find lower gas phase metallicity in the high redshift galaxies than in local sources with equivalent stellar mass and star formation rate, arguing against a time-invariant relation. While our result is preliminary and may be biased by measurement errors, this represents an important first measurement that will be further constrained by ongoing analysis of the full data set and by future observations.
We present a study of composite rest-frame ultraviolet spectra of Lyman break galaxies at z = 4 and discuss implications for the distribution of neutral outflowing gas in the circumgalactic medium. In general we find similar spectroscopic trends to those found at z = 3 by earlier surveys. In particular, absorption lines which trace neutral gas are weaker in less evolved galaxies with lower stellar masses, smaller radii, lower luminosity, less dust, and stronger Lyα emission. Typical galaxies are thus expected to have stronger Lyα emission and weaker low-ionization absorption at earlier times, and we indeed find somewhat weaker low-ionization absorption at higher redshifts. In conjunction with earlier results, we argue that the reduced low-ionization absorption is likely caused by lower covering fraction and/or velocity range of outflowing neutral gas at earlier epochs. This result has important implications for the hypothesis that early galaxies were responsible for cosmic reionization. We additionally show that fine structure emission lines are sensitive to the spatial extent of neutral gas, and demonstrate that neutral gas is concentrated at smaller galactocentric radii in higher redshift galaxies.
The results of this thesis present a coherent picture of galaxy evolution at high redshifts 2 ≲ z ≲ 4. Roughly 1/3 of massive star forming galaxies at this period are undergoing major mergers, while the rest are growing inside-out with star formation occurring in gravitationally unstable thick disks. Star formation, stellar mass, and metallicity are limited by outflows which create a circumgalactic medium of metal-enriched material. We conclude by describing some remaining open questions and prospects for improving our understanding of galaxy evolution with future observations of gravitationally lensed galaxies.</p
Non-Contiguous Protein Recombination
Get PDFSwapping sequence elements among related proteins can produce chimeric proteins with novel behaviors and improved properties such as enhanced stability. Although homologous mutations are much more conservative than random mutations, chimeras of distantly-related proteins have a low probability of retaining fold and function. Here, I introduce a new tool for protein recombination that identifies structural blocks that can be swapped among homologous proteins with minimal disruption. This non-contiguous recombination approach enables design of chimeras and libraries of chimeras with less disruption than can be achieved by swapping blocks of sequence. Less disruption means that one can generate libraries with higher fractions of functional enzymes and enables recombination of more distant homologs.
Using this new tool I design and construct many functional chimeric cellulases. I illustrate the structurally conservative nature of this recombination by creating a functional prokaryotic-eukaryotic chimera and solving its structure. I also show how non-contiguous recombination can be used to efficiently identify stabilizing mutations that have been incorporated into homologs in nature.</p