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A Search for Low-Mass Dark Matter with the Cryogenic Dark Matter Search and the Development of Highly Multiplexed Phonon-Mediated Particle Detectors
Get PDFA wide variety of astrophysical observations indicate that approximately 85% of the matter in the universe is nonbaryonic and nonluminous. Understanding the nature of this "dark matter" is one of the most important outstanding questions in cosmology. Weakly Interacting Massive Particles (WIMPs) are a leading candidate for dark matter since they would be thermally produced in the early universe in the correct abundance to account for the observed relic density of dark matter. If WIMPs account for the dark matter, then rare interactions from relic WIMPs should be observable in terrestrial detectors. Recently, unexplained excess events in the DAMA/LIBRA, CoGeNT, and CRESST-II experiments have been interpreted as evidence of scattering from WIMPs with masses ~10 GeV and spin-independent scattering cross sections of 10-41-10-40 cm2.
The Cryogenic Dark Matter Search (CDMS II) attempts to identify WIMP interactions using an array of cryogenic germanium and silicon particle detectors located at the Soudan Underground Laboratory in northern Minnesota. In this dissertation, data taken by CDMS II are reanalyzed using a 2 keV recoil energy threshold to increase the sensitivity to WIMPs with masses ~10 GeV. These data disfavor an explanation for the DAMA/LIBRA, CoGeNT, and CRESST-II results in terms of spin-independent elastic scattering of WIMPs with masses ≲12 GeV, under standard assumptions. At the time of publication, they provided the strongest constraints on spin-independent elastic scattering from 5-9 GeV, ruling out previously unexplored parameter space.
To detect WIMPs or exclude the remaining parameter space favored by the most popular models will ultimately require detectors with target masses ≳1 ton, requiring an increase in mass by more than two orders of magnitude over CDMS II. For cryogenic detectors such as CDMS, scaling to such large target masses will require individual detector elements to be fabricated more quickly and cheaply, while maintaining the nearly background-free operation of the existing experiment. We describe the development of athermal phonon mediated particle detectors using Microwave Kinetic Inductance Detectors (MKIDs), which could provide a simpler path to extending the CDMS detector technology to the ton scale. Results from prototype devices have demonstrated energy resolutions as good as σ = 0.55 keV at 30 keV, comparable to existing CDMS II detectors. Such designs can be scaled to kg-scale detector elements, while reducing the complexity of the detector fabrication and cryogenic readout electronics relative to existing designs. Since MKIDs are naturally multiplexed in the frequency domain, MKID-based designs also allow much finer pixelization of the phonon sensor, which is expected to enhance background rejection for large detectors while simultaneously reducing the number of wires needed to read out the detectors.</p
Essays in Neurofinance
Get PDFEconomists have learned a great deal about investor behavior over the last two decades with the availability of large discount brokerage data sets. While this has given economists a better understanding of the trading patterns that characterize individual investor behavior, less success has been achieved in understanding what drives these trading patterns. Part of the difficulty in this endeavor is that it is sometimes difficult to test alternative theories of investor behavior using only data from the field. In particular, the two trading patterns we investigate in this thesis, the disposition effect and the repurchase effect, are unlikely driven by standard rational models of trading, and alternative theories of their causes are difficult to test using only data from the field, or data from behavioral laboratory experiments.
In order to better understand the causes of the disposition effect and the repurchase effect, we use neural data, data collected from functional magnetic resonance imaging (fMRI) along with trading data to construct empirical tests of different theories. Chapter 1 uses fMRI data to test a model of realization utility, which can readily predict a disposition effect. In our experiment, we find that subjects exhibit strong disposition effects, although they are suboptimal, and the neural data strongly supports the realization utility hypothesis. While Chapter 1 is concerned with the selling behavior, we focus on systematic violations of buying behavior in Chapter 2. We propose a model of regret to explain the repurchase effect in the buy-side trading data, for which we find strong support in the neural data. Chapters 3 and 4 study whether the suboptimal trading behavior we find in the first two chapters is stable, and we explore what the source of the heterogeneity is. Specifically, in Chapter 3 we find that exogenously manipulating the display of information on the trading screen can significantly reduce the size of the disposition effect. Chapter 4 uses an approach from behavioral genetics to identify candidate genes that can help explain the cross-sectional variation in choice behavior.</p
Architecture, Dynamics, and Function of the General Stress Response System in B. subtilis
Get PDFCells exhibit diverse and dynamic responses to stress. However, in many cases it remains unclear what the dynamics are, how they are generated, and why they are beneficial to the cell or organism. To investigate these issues we studied the General Stress Response in B. subtilis, a critical, conserved stress signaling pathway, mediated by the alternative sigma factor, σB. First, we find that σB activates with stochastic, frequency modulated pulses in response to energy stress. We explore the mechanism behind this striking response and find that a small, compact circuit facilitates this behavior. Second, we find that σB activates with a single-homogenous pulse of activity exposed to environmental stress, in contrast to energy stress dynamics. We also find that activation is rate-responsive, and show how this property may separate broad and specific regulatory modes. Lastly, we present some preliminary work toward a synthetic sigma factor activation circuit. Combined, these results present a comprehensive study of σB activation and generate a platform by which other dynamic stress response systems can be understood
4d/2d Correspondence: Instantons and W-Algebras
Get PDFIn this thesis, we study the 4d/2d correspondence of Alday-Gaiotto-Tachikawa, which relates the class of 4-dimensional N=2 gauge theories (theories of class S) to a 2-dimensional conformal field theory. The 4d gauge theories are obtained by compactifying 6-dimensional N=(2, 0) theory of type A, D, E on a Riemann surface C. On the 2-dimensional side, we have Toda theory on the surface C with W-algebra symmetry, which is an extension of the Virasoro symmetry. In particular, the instanton partition function of the 4d gauge theory is reproduced by a conformal/chiral block of Virasoro/W-algebra. We develop techniques to compute the partition functions on 4d and 2d sides, for various gauge groups and matter fields.
We generalize the Alday-Gaiotto-Tachikawa 4d/2d correspondence to various cases. First, we study N=2 pure Yang-Mills theory with arbitrary gauge groups, including the exceptional groups. We explicitly construct the corresponding W-algebra currents, and confirm the correspondence holds at 1-instanton level. Second, we study the conformal quiver theory with Sp(1)-SO(4) gauge group. Finally, we study Sicilian gauge theories with trifundamental half-hypermultiplets. We also find that the conformal theories with Sp(1) gauge group and SU(2) gauge group have different instanton partition functions in terms of bare gauge couplings. We show this is an artifact of the renormalization scheme, by explicitly constructing a map between the bare couplings and studying its geometrical interpretations. This demonstrates the scheme independence of renormalization at the non-perturbative level.</p
Superconducting Microwave Resonator Arrays for Submillimeter/Far-infrared Imaging
Get PDFSuperconducting microwave resonators have the potential to revolutionize submillimeter and far-infrared astronomy, and with it our understanding of the universe. The field of low-temperature detector technology has reached a point where extremely sensitive devices like transition-edge sensors are now capable of detecting radiation limited by the background noise of the universe. However, the size of these detector arrays are limited to only a few thousand pixels. This is because of the cost and complexity of fabricating large-scale arrays of these detectors that can reach up to 10 lithographic levels on chip, and the complicated SQUID-based multiplexing circuitry and wiring for readout of each detector. In order to make substantial progress, next- generation ground-based telescopes such as CCAT or future space telescopes require focal planes with large-scale detector arrays of 104–106 pixels. Arrays using microwave kinetic inductance detectors (MKID) are a potential solution. These arrays can be easily made with a single layer of superconducting metal film deposited on a silicon substrate and pattered using conventional optical lithography. Furthermore, MKIDs are inherently multiplexable in the frequency domain, allowing ∼ 103 detectors to be read out using a single coaxial transmission line and cryogenic amplifier, drastically reducing cost and complexity.
An MKID uses the change in the microwave surface impedance of a superconducting thin-film microresonator to detect photons. Absorption of photons in the superconductor breaks Cooper pairs into quasiparticles, changing the complex surface impedance, which results in a perturbation of resonator frequency and quality factor. For excitation and readout, the resonator is weakly coupled to a transmission line. The complex amplitude of a microwave probe signal tuned on-resonance and transmitted on the feedline past the resonator is perturbed as photons are absorbed in the superconductor. The perturbation can be detected using a cryogenic amplifier and subsequent homodyne mixing at room temperature. In an array of MKIDs, all the resonators are coupled to a shared feedline and are tuned to slightly different frequencies. They can be read out simultaneously using a comb of frequencies generated
and measured using digital techniques.
This thesis documents an effort to demonstrate the basic operation of ∼ 256 pixel arrays of lumped-element MKIDs made from superconducting TiNx on silicon. The resonators are designed and simulated for optimum operation. Various properties of the resonators and arrays are measured and compared to theoretical expectations. A particularly exciting observation is the extremely high quality factors (∼ 3 × 107) of our TiNx resonators which is essential for ultra-high sensitivity. The arrays are tightly packed both in space and in frequency which is desirable for larger full-size arrays. However, this can cause a serious problem in terms of microwave crosstalk between neighboring pixels. We show that by properly designing the resonator geometry, crosstalk can be eliminated; this is supported by our measurement results. We also tackle the problem of excess frequency noise in MKIDs. Intrinsic noise in the form of an excess resonance frequency jitter exists in planar superconducting resonators that are made on dielectric substrates. We conclusively show that this noise is due to fluctuations of the resonator capacitance. In turn, the capacitance fluctuations are thought to be driven by two-level system (TLS) fluctuators in a thin layer on the surface of the device. With a modified resonator design we demonstrate with measurements that this noise can be substantially reduced. An optimized version of this resonator was designed for the multiwavelength submillimeter kinetic inductance camera (MUSIC) instrument for the Caltech Submillimeter Observatory.</p
Interkingdom Communication of a Bacterial Mutualist and its Mammalian Host
Get PDFMicrobial molecules have evolved to promote transient and/or permanent associations with mammals. Although numerous examples of secretion systems employed by pathogens during infection have been described, mechanisms by which commensal bacteria export molecules during symbiosis remain unknown. The human gut mutualist Bacteroides fragilis produces a capsular polysaccharide (PSA) that directs host immune development. We reveal herein that outer membrane vesicles (OMVs) deliver PSA to dendritic cells (DCs), promoting development of regulatory T cells and inducing anti-inflammatory cytokines during in vivo protection of intestinal disease. OMV mediated regulatory responses required the Growth Arrest and DNA-Damage-Inducible protein (Gadd45α) in DCs. DCs treated with OMVs containing PSA protect mice from experimental colitis, whereas Gadd45α-/- DCs are unable to support T cell regulatory response and are defective in suppressing proinflammatory cytokine production and host pathology. Our findings demonstrate DC-induced protection from disease via interaction with a beneficial microbial molecule delivered by OMVs, uncovering a novel paradigm for interkingdom communication between the microbiota and mammals.
In another effort to test the immunomodulatory activity of PSA outside of the gut, we found systemic treatment with PSA protects animals from experimental sepsis, a model for systemic inflammatory disease. More interestingly, this protection is mediated by B cells but not T cells because Rag-/- mice reconstituted with B cells gained the protection by PSA while those reconstituted with T cells were not protected. We further showed that a subset of B cells, marginal B cells, which are known to produce natural antibodies against bacterial antigens, were sufficient in mediating this protection. Preliminary data also suggested that secretion of IgM and/ or expression of type II Interleukin 1 receptor (IL-1R2) from marginal zone B cells might be critical for the suppression of the excessive inflammation during disease. This study will help to uncover the systemic effect of PSA, a microbial molecule from a gut commensal, and its potential as a novel therapy for human sepsis
Distance Based Visual Cues to Interpersonal Trust
Get PDFThis thesis examines the role of interpersonal spacing in determining the visual appearance and emotional response to images of faces. We present new methods for isolating the distance-dependent perspective projection as a visual feature, while controlling for confounding variables such as emotional expression. In behavioral experiments, we demonstrate the relevance of viewing distance to implicit social judgments, notably trust behavior in which real money was at stake. Finally, we provide tools for classifying face images according to viewing distance, and manipulating face images to simulate their appearance at different distances and different levels of trustworthiness
Genetic Regulatory Circuit Dynamics: Analysis and Synthesis
Get PDFHow can cells shape and utilize dynamic gene regulation to enable complex cellular behaviors? I study this question in natural and synthetic contexts.
The first project studies how a natural genetic network can imbue cells with a sense of ‘time’. It has long been known that environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable ‘polyphasic’ positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a timer that operates over time scales much longer than a cell cycle.
The second project proposes a method to rapidly generate and test complex genetic network dynamics in living cells. Existing microorganisms have evolved genetic circuitry to meet diverse challenges and maximize their survival and fitness. These challenges arise from external environmental pressures, or internal evolved constraints. Furthermore, these challenges may be either static or dynamic in nature. While existing circuits have likely evolved to be ‘good enough’ to respond to historical challenges, it remains unclear if they can be improved upon, and whether they respond well to novel situations. Synthetic biology seeks to engineer organisms with complex novel phenotypes, both to harness these novel organisms for a function and to understand their underlying biology. Dynamic gene expression strategies may be necessary to successfully generate these phenotypes. Unfortunately, generating novel dynamic gene expression patterns with conventional genetic engineering remains a challenge. Here I propose and describe progress towards a computerized feedback control setup to enable the programming and rapid testing of dynamic gene regulatory patterns in living cells. Small sets of genes will be regulated optogenetically based on programmed control laws, and past and present cellular state. This setup will enable us to explore the functions and limits of engineered dynamic gene regulation, while hopefully, in the process, providing lessons about the underlying biology.</p
The Structural Biology of HIV Budding and Maturation
Get PDFThe Human Immunodeficiency Virus (HIV) depends on the ability to exit infected cells, mature into an infectious state, and infect new host cells. The structural details of exiting and maturation (known as the "late stage events") remain elusive, but further understanding could lead to new therapies. HIV exits cells by hijacking a host cellular complex called ESCRT (Endosomal Sorting Complex Required for Transport), which evolved to constrict membranes in multivesicular body formation and cytokinesis. Electron cryotomography (ECT) was used to gain three-dimensional images of ESCRT in several contexts, including the physiological system of archaeal cell division. This study provided insight into the monomer interactions in the complex and led to a molecular mechanism of membrane constriction.
HIV is released from the cell as an immature particle with the main structural protein, Gag, forming a spherical shell around the RNA genome and enzymes. Gag is then cleaved into several proteins that refold and assemble into the conical capsid that is characteristic of the mature, infectious particle. The capsid is typically a closed cone, but unclosed varieties provide insight to the mechanism of assembly. By combining ECT, computer simulations, and fluorescence light microscopy, we analyzed features of unclosed capsids that suggest a "curling sheet" model of capsid assembly. These studies not only provided novel insight into the late stages of the HIV life cycle, but also contributed to the methods used by electron microscopists and researchers of HIV.</p
Synthesis, Characterization, and Reactivity Studies of Pyridine Bis(anilide) Iron Complexes
Get PDFThe unifying concept within this thesis is the investigation of pyridine bis(anilide) (NNN) iron complexes. Within this topic, chapter 1 speaks to the motivation behind studying these complexes, and how they relate to problems within iron catalysis in general. Chapter 2 introduces the general ligand design and the features which are thought to give unique and desirable properties to the complexes derived from it. The mesityl susbstituted ligand [MesNNN]H2 and subsequently ferrous ([MesNNN]Fe(THF)) and ferric ([MesNNN]FeI and ([MesNNN]Fe)2O) complexes are synthesized. The properties of the complexes are investigated using a variety of characterization techniques. Such techniques include paramagnetic 1H NMR spectroscopy, X-ray crystallography, Evans method, cyclic voltammetry, DFT calculations, and UV-vis spectrscopy. A detailed explanation of the challenges and solutions involved in using paramagnetic NMR are discussed. Crystallographic data indicate that the ligand framework confers a quite unusual geometry about the iron center, especially for the ferrous derivative [MesNNN]Fe(THF). The factors involved in this geometry are discussed, and DFT calculations supplement this discussion. Chapter 3 focuses on the reactivity of the iron complexes. Various oxidants and reductants were employed which interconvert the iron derivatives in chapter 2. Organometallic derivatives [MesNNN]FeR (R = hydride, alkyl, aryl) were not accessible, likely due to homolytic processes. L ligand exchange for [MesNNN]Fe(THF) was investigated. Ethylene reversibly binds, while cyclohexene does not. Trimethylphosphonium methylidene displaces THF to generate [MesNNN]FeCH2PMe3. Although the I oxidation state was accessible for [MesNNN]Fe(THF) electrochemically, attempts to chemically produce Fe I complexes based on the NNN ligand led to multiple products. Chapter 4 focuses on the intramolecular C-H activation of [MesNNN]Fe(THF) with RN3 to afford [MesNNN-NHR]Fe (R = SiMe3, adamantyl). The kinetics of the reaction with Me3SiN3 was investigated in detail, and a mechanism was proposed. Iron complexes based on the pincer ligands [tBuNNN] and [ONO] were investigated