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The Development and Performance of the First BICEP Array Receiver at 30 and 40 GHz for Measuring the Polarized Synchrotron Foreground
Get PDFThe existence of the CMB marks a big success of the lambda cold dark matter standard model, which describes the universe’s evolution with six free parameters. The inflationary theory was added to the picture in the ’80s to explain the initial conditions of the universe. Scalar perturbations from inflation seeded the formation of the large-scale structure and produced the curl-free E-mode polarization pattern in the CMB. On the other hand, tensor fluctuations sourced primordial gravitational waves (PGW), which could leave unique imprints in the CMB polarization: the gradient-free B-mode pattern. The amplitude of B modes is directly related to the tensor-to-scalar ratio r of the primordial fluctuations, which indicates the energy scale of inflation. The detection of the primordial B modes will be strong supporting evidence of inflation and give us opportunities to study physics at energy scales far beyond what can ever be accessed in laboratory experiments on the Earth.
Currently, the main challenge for the B-mode experiments is to separate the primordial B modes from those sourced by matter between us and the last scattering surface: the galactic foregrounds and the gravitational lensing effect. The two most important foregrounds are thermal dust and synchrotron, which have very different spectral properties from the CMB. Thus the key to foreground cleaning is the high sensitivity data at multiple frequency bands and the accurate modeling of the foregrounds in data analyses and simulations. In this dissertation, I present my work on ISM and dust property studies which enriched our understanding of the foregrounds.
The BICEP/Keck (BK) experiments build a series of polarization-sensitive microwave telescopes targeting degree-scale B-modes from the early universe. The latest publication from the collaboration with data taken through 2018 reported tensor-to-scalar ratio r0.05 < 0.036 at 95% C.L., providing the tightest constraint on the primordial tensor mode.
BICEP Array is the latest generation of the series experiments. The final configuration of the BICEP Array has four BICEP3-class receivers spanning six frequency bands, aiming to achieve σ(r) ≾ 0.003. The first receiver of the BICEP Array is at 30 and 40 GHz, constraining the synchrotron foregrounds. In this dissertation, I cover the development of this new receiver focusing on the design and performance of the detectors. I report on the characterizing and diagnosing tests for the receiver during its first few observing seasons.</p
A Millifluidic Bulge Test for Multiscale Properties of Engineered Biofilms
Get PDF Biofilms – communities of bacterial cells associated with their extracellular polymeric matrices – are complex materials whose features span many length scales, ranging from bulk cohesive material properties, to mesoscale structural and compositional heterogeneity, down to the microscopic cellular morphology and cell-cell interaction chemistry.
Here, we demonstrate a tool to study the mechanical properties of biofilms across length scales from the mesoscale (0.2 mm) to the bulk (1 mm) using a simplified model system based on genetically engineered E. coli. Using a custom millifluidic device that suspends a 3 mm dia. biofilm across a support, we impose tunable hydrostatic pressure drops in the Pa-kPa range across the biofilm. The resulting deformation of the film through an aperture is visualized with optical coherence tomography and used to estimate bulk and mesoscale mechanical properties of the film. Our method requires only microliters of material, causes minimal disruption to the film structure, and allows for estimates of both average properties as well as local heterogeneity as a function of cell-cell interaction chemistry and biofilm damage and healing. In the final chapter we introduce other model biofilm systems for their unique optical and mechanical properties. </p
Searching for Gravitational Waves from Compact Binary Coalescences and Stochastic Backgrounds in the LIGO–Virgo Detector Network
Get PDFGravitational waves (GWs) are ripples in spacetime generated by accelerating masses, carrying away information about the underlying processes. There are four main astrophysical sources detectable in the sensitive band of the LIGO–VIRGO–KAGRA (LVK) GW detector network: compact binary coalescences, burst sources, continuous waves and stochastic gravitational-wave backgrounds. This thesis focuses on the detection methods of two of these categories, coalescing compact binaries and stochastic backgrounds, and their search results across LIGO–Virgo’s first three observing runs spanning from 2015 to 2020.
Compact binary coalescences of black holes and/or neutron stars are the only type of GW sources detected so far in the LVK frequency band. Such binary systems lose orbital energy via GW emission and are compact enough to merge within the age of the Universe. PyCBC is a matched-filter, all-sky pipeline for GW signals from compact binary mergers using a bank of modeled gravitational waveform templates. We describe the methods employed in PyCBC and present the developmental updates both in its archival and low-latency configurations for LIGO–Virgo’s third observing run. Using PyCBC to analyze the data from LIGO–Virgo’s first three observing runs, we summarize our results of the searches in gravitational-wave transient catalogs and characterize some exceptional events.
A stochastic gravitational-wave background consists of a large number of weak, independent and uncorrelated events of astrophysical or cosmological origin. The GW power on the sky is assumed to contain anisotropies on top of an isotropic component, i.e., the angular monopole. Complementary to the LVK searches, we develop an efficient analysis pipeline to compute the maximum-likelihood anisotropic sky maps in stochastic backgrounds directly in the sky pixel domain using data folded over one sidereal day. We invert the full pixel-pixel correlation matrix in map-making of the GW sky, up to an optimal eigenmode cutoff decided systematically using simulations. In addition to modeled mapping, we implement a model-independent method to probe spectral shapes of stochastic backgrounds. Using data from LIGO–Virgo's first three observing runs, we obtain upper limits on anisotropies as well as the isotropic monopole as a limiting case, consistent with the LVK results. We also set constraints on the spectral shape of the stochastic background using this novel model-independent method.</p
Stem Cell-Derived Embryo Models in Mouse and Human to Illuminate the “Black Box” of Pre- to Post-Implantation Development
Get PDFMammalian development is a complex and highly regulated process by which a single cell, the totipotent zygote, gives rise to all lineages of the future organism. While incredible advancements have been made to study and understand the earliest events of our life, many questions are still unanswered. Moreover, the most precarious stage of development, implantation, remains a “black box” to researchers due to inaccessibility of the embryo within the uterus of the mother. In the last decade, however, the emergence of stem cell derived embryos represents an exciting alternative avenue to study these dynamic stages.
During my PhD, I worked to establish two pre-implantation stem cell models, one in human and one in mouse, to better understand the earliest days of mammalian development. These models replicate the blastocyst stage of development; at this point in time the embryo is ready to implant into the uterus and contains all embryonic and extra-embryonic tissues needed to form the future organism: the epiblast, the hypoblast, and the trophectoderm. Beginning with my human model, I demonstrate the ability of a single cell type, expanded potential stem cells (EPSCs), to give rise to structures that replicate the natural blastocyst in size, morphology, and initiation of lineage segregation. Furthermore, these human blastocyst-like structures can undergo the very beginning of post-implantation remodeling by forming an epiblast rosette and initiating lumenogenesis. Nevertheless, single cell RNA-seq (scRNA-seq) analysis reveals that lineages are not fully committed in this model, perhaps explaining why development is limited in these structures up to about Day 7/8. In the context of my mouse model, I combine not one but three distinct cell types to generate blastocyst-like structures: 1) wildtype embryonic stem cells (ESCs) to form the epiblast, 2) trophoblast stem cells (TSCs) to form the trophectoderm, and 3) Gata4-inducible ESCs to form the primitive endoderm. Again, these structures mimic the natural mouse blastocyst in morphology and lineage segregation and demonstrate the ability to transition to post-implantation stages. Development of the three blastocyst lineages was further confirmed via global scRNA-seq analysis comparing our Gata4i-Blastoids to natural embryos; importantly, however, this analysis also showed that differentiation of the mural trophectoderm, the tissue responsible for uterine invasion, is lacking in our stem cell model and likely explains the inability for these blastoids to implant in vivo.
Altogether, this dissertation explains key aspects of pre- to post-implantation development and highlights the incredible power of stem cell-derived embryos to self-organize into structures that closely mimic the natural embryo.</p
Thermally and Mechanically Responsive Platforms for Functional Polymeric Materials
Get PDFConnecting a polymer’s reactivity or properties to its working environment is a grand challenge in polymer chemistry. Research towards this goal is driven both by a fundamental interest in mimicking nature’s ability to create surfaces that adapt to their surroundings and a practical desire to tailor the properties of materials to the wide-ranging contexts where they find use. This thesis investigates the development of polymers that exhibit productive changes in physical properties or chemical reactivity under an applied environmental stimulus
A Novel, Rapid Phenotypic Assay for a Beta-Lactam Antibiotic Susceptibility and an Analysis of its Theoretical Limits
Get PDFCurrent management of bacterial infections is limited by the slow turnaround time of culture-based antibiotic susceptibility testing (AST). Culture-free phenotypic AST methods, though faster, are limited not only by analytical sensitivity but also by the low number, density, and purity of live pathogens present in clinical specimens before culturing. Separating and concentrating pathogens from clinical specimen matrices and improving the analytic sensitivity of phenotypic measurement technologies remain active areas of research. However, to date, the literature lacks consensus over what is a reasonable goal for the minimum number of pathogens in a clinical specimen needed to accurately perform phenotypic AST.
I describe "bulk filtration AST" and "digital filtration AST," two new filtration-based AST methods that improve an AST method previously published by others and myself. These methods use nucleic acid quantification to assess the activity of antibiotic classes (and only those classes) targeting peptidoglycan turnover, specifically the beta-lactams, which are the most frequently prescribed class of antibiotics. I use filtration AST to quantify the in vitro pharmacodynamics of beta-lactam antibiotics over time scales shorter than two hours, and I simultaneously validate the methods' accuracies on clinical isolates of Enterobacteriaceae. To analyze filtration AST results, either for fitting parameter values or for predicting susceptibility, I derive probabilistic models for the outcomes of each of the two filtration AST methods, then perform Bayesian parameter inference from my data.
I then propose a general mathematical framework for defining the concepts of the phenotypic assay and the ideal phenotypic assay. Within this framework, I calculate the ideal filtration AST performance as a function of the number of cells assayed, my fitted pharmacodynamic parameters, and other variables. Interestingly, the observed performance of my implementation of digital filtration AST is consistent with the implementation's approaching the ideal performance. I hope my demonstration of these new methods and my theoretical framework will help guide future research into rapid phenotypic AST.</p
Constraints on the Polarized Dust and the Cosmic Microwave Background Using BICEP / Keck Array Series of Telescopes
Get PDFBK18 data consists of all the data taken by the Bicep2, Keck Array, and Bicep3 CMB polarization experiments, as well as publicly available WMAP and Planck maps. The Q/U maps reach depths of 2.8, 2.8 and 8.8 µKCMB arcmin at 95, 150, and 220 GHz respectively over an effective area of ~ 600 square degrees at 95 GHz and ~ 400 square degrees at 150 and 220 GHz. The likelihood analysis yields r < 0.036 at 95% confidence, with unbiased simulations yielding σ(r)=0.009. The multi-component model that is used in the likelihood analysis consists of lensed-ΛCDM, tensor modes, and polarize dust and synchrotron components. Foreground model consists of thirteen parameters, some of which are estimated in the likelihood analysis with priors derived from larger regions of sky from WMAP and Planck: amplitude, spectral index, and spatial index for dust and sync, as well as their spatial correlation; dust frequency decorrelation and tensor-to-scalar-ratio. Spectral index for dust emission no longer requires a prior taken from measurements on other regions of the sky.
In the BK papers, EE spectra are not used to derive the model, however the spectra agree well with the assumption that EE/BB = 2 for dust. In this thesis we expand on this assumption, sharing the results for the EE/BB estimate for dust when this is a free parameter in the likelihood calculation. We use the map-based and spectral-based band difference approaches to include E-modes in the likelihood analysis. In the BK papers, dust parameters are assumed to be constant over the sky. We will go over the likelihood work on the spatial constraints for the dust spectral index to examine the validity of this assumption.</p
Mechanistic Investigations and Development of Ni-Catalyzed Cross- Electrophile Coupling Reactions
Get PDFTransition metal-catalyzed cross-coupling reactions have proven to be a powerful technology for the modular construction of carbon-carbon and carbon-heteroatom bonds over the last half century. More recently, reductive cross-coupling catalyzed by nickel has emerged as a complementary synthetic approach that couples electrophilic fragments and is rendered catalytic by the inclusion of a terminal reductant. These reactions are advantageous because the use electrophiles as coupling partners which display greater stability, functional group tolerance, and commercial availability over the corresponding nucleophilic coupling partners. Additionally, Ni catalysts are less prone to β-hydride elimination compared to later transition metals which enables C(sp³)–C(spⁿ) couplings. The challenge with using coupling partners of the same polarity is developing a catalyst that can activate each electrophile in a mechanistically distinct way in order to get high levels off cross-selectivity, over statistical mixtures of cross- and homocoupled products.
Herein, we describe a mechanistic investigation on Ni-catalyzed cross-electrophile couplings developed in our lab; specifically, the asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters and benzylic chlorides. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp³) activation changes from a Ni-mediated process when benzyl chlorides and Mn⁰ are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a Ni^(ɪɪ)–alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.
Efforts to expand the scope of coupling partners in XEC reactions to include novel classes of electrophiles, such as N-alkyl imines, are also described. The preparation of heterobenzylic amines by a Ni-catalyzed reductive cross-coupling between heteroaryl imines and C(sp³) electrophiles is reported. This umpolung-type alkylation proceeds under mild conditions, avoids the pre-generation of organometallic reagents, and exhibits good functional group tolerance. Mechanistic studies are consistent with the imine substrate acting as a redox-active ligand upon coordination to a low-valent Ni center. The resulting bis(2-imino)heterocycle·Ni complexes can engage in alkylation reactions with a variety of C(sp³) electrophiles, giving heterobenzylic amine products in good yields.</p
Essays on Social Learning and Social Choice
Get PDFThis dissertation contains three essays, two which contribute to the study of social learning (Chapters 1 and 2) and one which contributes to the study of social choice (Chapter 3).
In Chapter 1, I introduce a fully rational model of social learning on networks with endogenous action timing. I show that the structure of the network can play an important role in the aggregation of information. When the social network contains high-degree vertices, agents can be arbitrarily likely to make good choices. In contrast, when the social network is linear, there is a bound on how likely agents are to make good choices which holds regardless of how patient they are. The main contribution of this chapter is the identification of a novel mechanism through which strategic behavior can substantially impede the flow of information through a social network.
In Chapter 2, co-authored with Vadim Martynov and Omer Tamuz, we study the asymptotic rate at which the probability of taking the correct action converges to 1 in the classical sequential learning model with unbounded signals. We provide a characterization of the asymptotic law of motion of the public belief, and we use this characterization to show that convergence occurs more slowly than when agents directly observe private signals, and that the expected time until the last incorrect action can be finite or infinite.
In Chapter 3, co-authored with Laurent Bartholdi, Maya Josyula, Omer Tamuz, and Leeat Yariv, we introduce equitability as a less stringent alternative to symmetry for modeling egalitarianism in voting rules. We then use techniques from group theory to show that equitable voting rules can have minimal winning coalitions comprising a vanishing fraction of the population, but they cannot be smaller than the square root of the population size.</p
Total Synthesis of Lupin Alkaloids, Diterpenoid Alkaloids, and Progress Towards the Myrsinane Diterpenes
Get PDFThe interplay between total synthesis and methodology is a driver of innovation in organic synthesis. Challenging bond formations in complex systems necessitate the development ever more robust new reactions, which intern can enable more efficient syntheses. The need for powerful synthetic organic chemistry can’t be understated because of its utility in applications such as medicine, petrochemicals, plastics, and agrichemicals.
Herein, we present how total synthesis drives innovation in organic chemistry. First, a novel cyclization reaction between pyridine and glutaryl chloride is discussed, which has enabled the synthesis of seven lupin alkaloids. Next, the development of a convergent fragment coupling tactic based upon the semi-pinacol rearrangement is evaluated for its generality inspired by the total synthesis of several C19 diterpenoid alkaloids. Lastly, a convergent fragment coupling approach is applied to the total synthesis of falcatin A based upon a Mukaiyama Michael tandem Mukaiyama aldol reaction.</p