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Mitigating Noise in Interferometric Gravitational Wave Detectors
Get PDFGravitational waves, first predicted by Einstein in 1916, eluded detection for nearly a century. These faint ripples in the fabric of spacetime, with typical strain amplitudes at the Earth on the order of |h| ∼ 10−22, carry secrets of the universe untold by electromagnetic radiation. Following decades of research and development, a network of terrestrial interferometric detectors succeeded in measuring the passing of a gravitational wave (GW150914) for the first time in 2015. Individual detectors within this network are currently said to be operating in a “second-generation” configuration; over the next decade, planned upgrades will take these detectors beyond this into a new generation. This thesis concerns the characterization and reduction of noise in one of these second-generation detectors, Advanced LIGO, as well as efforts underway to improve its sensitivity in the coming years.
The first part of this thesis is a detailed overview of gravitational waves, the history of gravitational wave detection, and a reasonably thorough description of the Advanced LIGO detector. Particular attention is paid to a pedagogical motivation of the optical configuration of Advanced LIGO with reference to its forebears. This part ends with an overview of the sources of noise limiting the sensitivity of Advanced LIGO, and an exposition of plans to reduce their influence in the future.
The second part describes the development of a laser gyroscope for use in tilt sensing in Advanced LIGO, starting with a motivation of the work based on limitations in the area of seismic noise sensing and cancellation.
The third part recounts the design, fabrication, testing, installation and commissioning of an important component of the Advanced LIGO detector: the output mode cleaner (OMC).
The fourth part outlines a proposed scheme for reduction of quantum noise in gravitational wave detectors and other experiments. In particular, this scheme allows for the operation of a so-called “optical spring” cavity in such a way as to be largely immune from the deleterious effects of quantum radiation pressure noise.
The fifth and final part describes progress towards a direct measurement of thermal noise in thin silicon ribbons, which is pertinent to the design of suspensions in future cryogenic gravitational wave detectors.
This thesis has the internal LIGO document number P1900035.</p
Use of Recombinant Self-Associating Proteins for Altering Cellular Fate and Behavior
Get PDFThe behavior of mammalian and bacterial cells is governed by their surroundings, and the interactions of cells with their nearest neighbors. In this work, I will demonstrate how self-associating proteins such as leucine zippers or SpyTag and SpyCatcher can be used either in hydrogels for cell culture, or to drive the aggregation of cells into artificial, engineered communities. I further demonstrate how these self-associating protein-based materials can either alter the fate of cultured cells, or directly change cellular behavior through the activation of a quorum sensing circuit.
In the first chapter, I discuss protein-based methods for making different types of organoids. Organoids are groups of cells derived from stem or progenitor cells that form a multicellular structure consisting of different cell types. These organoids are currently of interest as disease model systems, pharmaceutical test platforms, and replacement tissues. However, most studies of organoids to date have derived them from Matrigel-based cultures. While versatile and inexpensive, Matrigel is undefined, suffers from batch-to-batch variability, and its xenogeneic nature means that organoids derived from Matrigel are unlikely to be approved for clinical use. In Chapter 1, I review current state-of-the-art materials developed as alternatives to Matrigel, such as naturally-derived extracellular matrices, synthetic hydrogels, and recombinant proteins serving as artificial extracellular matrices. I consider the advantages and disadvantages of each method, as well as speculate on possible future directions for the field.
Of these alternatives to Matrigel, recombinant protein-based artificial extracellular matrices have the advantage of being easy to engineer, as genetic encoding of the material allows precise control over molecular weight and functionality. Development of these types of materials has long been a focus of work in our laboratory, and in Chapter 2, I discuss the development of two protein-based hydrogels expressed in Escherichia coli, which are based on a previously-reported PEP hydrogel. These new “PEXEP-type” hydrogels are physically cross-linked by leucine zippers derived from rat cartilage oligomeric matrix protein (COMPcc), incorporate chemical cues from fibronectin and collagen IV, and were used for pancreatic cell culture in defined medium. When comparing this defined, protein-based medium to methylcellulose-Matrigel, we find that the growth of endocrine cells is promoted, as opposed to the ductal cells found in methylcellulose-Matrigel culture. We further find a difference in colony types observed based on whether the fibronectin or collagen IV cue is present. More interestingly, the protein-based culture material promotes the growth of endocrine progenitor cells, which may be useful for further studying the formation of the Islets of Langerhans. Finally, we observe that sorted populations of murine cells cultured in our protein hydrogels have a lower rate of colony formation, and this reduction in the number of colonies is not observed in methylcellulose-Matrigel culture. We believe that this might be evidence for a paracrine effect that promotes cell growth, particularly the growth of putative endocrine colonies, though further experiments are required to confirm this effect.
In Chapter 2, I demonstrate how a self-associating protein can be used to change the fate of a cell culture, and give rise to multicellular colonies. However, for the purpose of constructing bioreactors, microbial fuel cells, or systems for environmental remediation, it may be advantageous to design tissue-like systems de novo, making multifunctional communities of bacteria that function as artificial tissues. In Chapter 3, I will discuss the construction of a synthetic microbial community of E. coli cells, whose quorum sensing response is governed by aggregation of the cells. This aggregation in turn is driven by the expression of surface-displayed self-associating proteins, and I will discuss methods developed to control the size, reversibility, and morphology of these aggregates. As the behavior of these aggregates is dependent on cell-cell communication facilitated by proximity, these consortia represent early examples of synthetically-designed artificial tissues that can be governed by engineered cell-cell signaling.</p
Tunable Thermal Bioswitches as a Control Modality for Next Generation Therapeutics
Get PDFSynthetic biology is rapidly contributing to the field of therapeutic development to create increasingly potent agents for the treatment of a variety of diseases. These living "designer therapeutics" are capable of integrating multiple sensory inputs into decision making processes to unleash an array of powerful signaling and effector responses. Included in the great therapeutic potential of these agents, however, is a cognate risk of severe toxicity resulting from runaway on-target or erroneously induced off-target activity. The ability to remotely control engineered therapeutic cells after deployment into patient tissue would drastically reduce the potential dangers of such interventions. However, among existing biological control methods, systemic chemical administration typically lacks the spatial precision needed to modulate activity at specific anatomical locations, while optical approaches suffer from poor light penetration into biological tissue. On the other hand, temperature can be controlled both globally and locally — at depth — using technologies such as focused ultrasound, infrared light and magnetic particle hyperthermia. In addition, body temperature can serve as an indicator of the patient's condition. Overall, temperature is a versatile signal which can provide a handle to actuate a biological response for the control of therapeutic agents.
In this thesis, a tunable and modular system is developed to respond to thermal perturbations in cellular environments and affect a biological response. At the core of this system is a pair of single-component thermosensing proteins whose dimerization is strongly and sharply coupled to their thermal environment. These domains are first utilized in their native context as negative regulators of transcription in prokaryotes, wherein they are integrated into genetic circuits to control expression of reporter genes. These gene circuits show strong and sharp thermal activation and can be utilized in multiplex to affect higher order logical operations. Cells imbued with these circuits demonstrate transcriptional activation upon global thermal elevation within the host animal within which they reside (fever) or upon a spatiotemporally localized temperature shift imparted by focused ultrasound hyperthermia. In subsequent work, one of these bioswitches is introduced into mammalian cells where it functions as a modular Protein-Protein Interaction (PPI) domain, conferring temperature-dependent protein localization.
The work conducted in this thesis demonstrates the feasibility of utilizing temperature as a stimulus for biological activity. This technology can be harnessed to regulate therapeutically relevant processes in bacterial and mammalian cells such as transcriptional regulation and protein localization, and potentially broader protein function. The thermal bioswitches described herein could be utilized to engineer an array of research tools and biological therapies with actuation driven by spatiotemporally precise noninvasively applied stimuli or by real-time sensing of host conditions.</p
A Perturbative Model for the Intrinsic Alignments of Galaxies
Get PDFIntrinsic alignments (IA), correlations between the intrinsic shapes and orientations of galaxies on the sky, are both a significant systematic in weak lensing and a probe of the effect of large-scale structure on galactic structure and angular momentum. In the era of precision cosmology, it is thus especially important to model IA with high accuracy.
Efforts to use cosmological perturbation theory to model the dependence of IA on the large-scale structure have thus far been relatively successful. However, extant models have not been made fully self-consistent to arbitrary order in perturbation theory and do not consistently account for time evolution. In particular, advection of galaxies due to peculiar velocities alters the impact of IA, because galaxy positions when observed are generally different from their positions at the epoch when IA is believed to be set.
In this work, we evolve the galaxy IA from the time of galaxy formation to the time at which they are observed, including the effects of this advection, and show how this process naturally leads to a dependence of IA on the velocity shear. We then incorporate this time evolution into a fully self-consistent perturbative formalism for a passively evolving IA model. We demonstrate this formalism first at second order as a proof of concept, then at third order for application to observationally relevant two-point correlations at one-loop order.
We also discuss the implications of the time-evolved IA model for systematic errors in weak lensing as well as for studies of galaxy formation and evolution. We find that considering advection introduces nonlocality into the bispectrum, and that the degree of nonlocality represents the memory of a galaxy's path from the time of its formation to the time of observation. We discuss how this result can be used to constrain the redshift at which IA is determined and provide Fisher estimation for the relevant measurements using the example of SDSS-BOSS.</p
Scalable Nanophotonic Light Management Design for Solar Cells
Get PDFThe current trend in wide adoption of solar energy is encouraging in the context of current projections of increasing energy consumption and the dire need to decrease carbon emissions. The solar industry has expanded due to scientific advances in the power conversion efficiency of solar modules. In order maintain a rapid pace of adoption and further decrease electricity costs, converting each photon becomes increasingly important. This work focuses on nanophotonic approaches to increasing the power conversion efficiency of different solar photovoltaic designs. The projects voluntarily impose certain design constraints in order to be compatible with the large scale manufacturing needed by the solar industry. A focus was given to designs that can leverage the promising technology of nanoimprint lithography. Amorphous silicon tandem cells with embedded nanophotonic patterning attempted to increase absorption while minimizing materials and time costs. Simulated designs of Copper Indium Gallium Diselenide absorbers showed that the management of excited carriers is equally as important as light management in decreasingly thin absorber layers. Near perfect anti-reflection structures were given a detailed physical analysis to better describe the fundamental physics of near zero reflection due to nanocones printed on solar cell encapsulation glass. Experimental results agreed with the theoretical analysis, and showed that these nanostructures further increased absorbed photocurrent by trapping light in the encapsulation glass. Finally, a unique device in the form of a tandem luminescent solar concentrator/silicon solar module was proposed and analyzed as a low cost and adaptable technology for increased solar power conversion efficiency. Key to this design was discovery of new, near-perfect components for light management. Exciting and innovative designs are proposed to control the light-matter interaction within these devices. Study of a photonic luminescent solar concentrator predicted that luminescence can be trapped in photonic crystal slab waveguides with near zero loss. Rigorous experimental efforts to characterize a multitude of near-perfect samples help guide these designs toward their final goals
Development and Mechanistic Studies of Ni-Catalyzed Asymmetric Reductive Cross-Coupling Reactions
Get PDFCross-coupling reactions have emerged as powerful methods to form carbon-carbon and carbon-heteroatom bonds in a vast array of synthetic contexts. Nickel-catalyzed reductive cross-coupling reactions have opened up a new mode of reactivity, allowing for the cross-coupling of bench-stable electrophiles as both coupling partners. Asymmetric variants, which use a chiral ligand, increase molecular complexity by introducing stereocenters with high levels of enantioselectivity. Application of this methodology to an array of electrophiles has led to the development of a number of transformations incorporating both C(sp2)-hybridized electrophiles (aryl iodides, alkenyl bromides, and acyl chlorides) and C(sp3)-hybridized electrophiles (benzyl chlorides and α-chloronitriles).
Herein we discuss our most recent efforts in the development and application of Ni-catalyzed asymmetric cross-coupling reactions with alkenyl electrophiles. First, the expansion of our previously developed methodology has allowed for bulky trimethylsilyl groups on the benzyl chloride electrophile, providing chiral allylic silane products in good yield and enantioselectivity. The utility of these products with both traditional and newly developed methodology is highlighted. Following this, we describe the development of reaction conditions that proceed with benzyl N-hydroxyphthalimide esters. This approach proceeds through a decarboxylative strategy, generates previously accessible radical intermediates, and proceeds with the use of a homogenous reductant. Our investigations into the mechanism on the cross-coupling of alkenyl bromides and benzyl chlorides is also disclosed, where we first identified the formation of alkenyl chloride and alkenyl iodide intermediates under the reaction conditions. This inspired us to develop a Ni-catalyzed alkenyl triflate halogenation in order to prepare alkenyl halide synthetic intermediates.</p
Neural Architecture Underlying Thirst Regulation
Get PDFAn important aspect of thirst is its quick quenching. When thirsty, you drink a glass of water for a few seconds; the water travels from the mouth to the stomach and you are satiated. The water has not yet been absorbed into the blood, so the brain needs to have mechanisms to signal stopping of drinking. It cannot simply depend on the body, as the body takes a good 15 - 30 minutes to even start absorption.
In this dissertation, I describe dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids, the consequent drinking behavior, and reward processing to maintain internal water balance.
In Chapter 1, I show how neural populations in the lamina terminalis, a forebrain structure, form a hierarchical circuit architecture to regulate thirst. Among them, excitatory neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Thirst-driving neurons in the SFO receive temporarily distinct preabsorptive inhibition by drinking action and gastrointestinal osmolality sensing. A distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of these neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion.
In Chapters 2 and 3, I talk about how thirst triggers a strong motivational state that drives animals toward drinking behavior. The consequent fluid intake provides both satiation and pleasure of drinking to animals. However, how these two factors are processed and represented by the brain remains poorly understood. Here I will use in vivo optical recording, genetics, and intragastric infusion approaches to dissect thirst satiation circuits and their contribution to reward signals. Thirst-driving neurons in the subfornical organ (SFO) receive multiple temporally-distinct satiation signals prior to the homeostatic recovery: oropharyngeal stimuli induced by drinking action and gastrointestinal sensing of osmolality changes. In chapter 1, I have shown that drinking action is represented by inhibitory neurons in the median preoptic nucleus (MnPO). Here, I demonstrate that gut osmolality signals are mediated by specific GABAergic neurons in the SFO. These neurons were selectively activated by hypo-osmotic stimuli in the gut independent of drinking action. Optogenetic gain- and loss-of-function of this inhibitory population suppressed and increased water intake in thirsty animals, respectively. These results indicate that oropharyngeal- and gastrointestinal-driven satiation signals are transmitted to thirst neurons through different neural pathways. Furthermore, I investigated the contribution of thirst satiation signals to the reward circuit using a genetically-encoded ultrafast dopamine (DA) sensor. Interestingly, oral ingestion but not gut osmolality changes triggered robust DA release. Importantly, chemogenetic activation of thirst-quenching neurons did not induce DA release in water-deprived animals. Together, this dissected genetically-defined thirst satiation circuits, the activity of which are functionally separable from reward-related brain activity. Taken together, these finding provide answers to some longstanding questions in the neural control of fluid intake, and appetite in general.</p
I. Shape Selectivity of Small-pore Molecular Sieves for the Methanol-to-Olefins Reaction and II. Synthesis and Topotactic Transformation of Germanosilicate CIT-13
Get PDFThis thesis presents research results from two projects involving molecular sieves. These investigations concern their synthesis, characterization and use as heterogeneous catalysis.
In part I, the shape selectivity in the methanol-to-olefins (MTO) reaction is studied, and a new molecular sieve structure – MTO reaction selectivity relationship is developed. 17 zeolites and 13 phosphate-based molecular sieves having 14 selected cage-type/small-pore topologies (CHA, AFX, SFW, LEV, ERI, DDR, AEI, RTH, ITE, SAV, LTA, RHO, KFI, and UFI) are synthesized. The MTO reaction is performed using these catalysts at the same reaction conditions.
The reaction results lead to the conclusion that the molecular sieve cage topology is the most important structural factor that primarily determines the olefin product distribution. For example, AEI and CHA are synthesized with four different elemental compositions (zeolite, SAPO, CoAPO, MgAPO). Regardless of differences in elemental compositions, very similar product distribution patterns are observed in each of the isostructural groups of molecular sieves. Additionally, other isostructural pairs of SAPOs and zeolites show similar product distributions.
The reaction results from 14 topologies are grouped into four categories. Category I consists of CHA, AFX, SFW, and other GME-related topologies. Catalysts having these topologies show ethylene-to-propylene ratios close to one. Category II is a group of ERI and LEV which generate more ethylene than propylene. Category III is a group of DDR, AEI, RTH, ITE, and SAV which shows propylene selectivities higher than those of ethylene. Category IV is a group of LTA, RHO, KFI, and UFI which possess LTA-cages. These types of catalysts give high butylene selectivities.
The concept of cage-defining ring and its size is introduced as a reliable geometric indicator on the basis of a hypothetical ellipsoid cage model. The cage-defining ring size can be easily calculated from crystallographic information which is available online. A strong correlation is found between the cage-defining ring sizes and the four categories of reaction behavior.
In part II, an extra-large-pore germanosilicate molecular sieve CIT-13 with 14- and 10-ring pores is synthesized using monoquaternary, methylbenzylimidazolium-derivative OSDAs, and the synthesis conditions are optimized. Fluoride-free synthetic pathways for pure germanosilicate CIT-13 and isomorphous aluminum substitution in synthesis of aluminogermanosilicate CIT-13 are also described. The nature of disorder in the arrangement within CIT-13 framework is discussed, and its physicochemical properties compared to a UTL-type germanosilicate IM-12.
A comprehensive network of topotactic transformation and postsynthetic modification pathways starting from germanosilicate CIT-13 (Ge-CIT-13) is described. The moisture-mediated transformation of Ge-CIT-13 into another extra-large-pore CFI-type germanosilicate (Ge-CIT-5) is discovered, and the role of sorbed water in the transformation kinetics studied. The resultant Ge-CIT-5 is the first germanosilicate molecular sieve having a CFI topology, and the corresponding transformation is also the first inter-germanosilicate transformation occurring at room temperature. The microporosity of Ge-CIT-5 matched well with the reference pure-silica CIT-5 synthesized using the sparteine-type OSDA.
The acid-delamination processes of Ge-CIT-13 and Ge-CIT-5 are investigated. Ge-CIT-13 can be transformed into two new frameworks, CIT-14 with 12- and 8-ring pores and CIT-15 with 10-ring pores, on the basis of an ADOR-type topotactic transformation. The inverse sigma transformation of Ge-CIT-13 directly into CIT-14 is also firstly described. The conventional acid-delamination of Ge-CIT-13 does not yield Ge-CIT-5. However, the CIT-15-type material is obtained via the base-delamination pathway from Ge-CIT-5. The postsynthetic alumination of Ge-CIT-13 and Ge-CIT-5 is also achievable.</p
Understanding Geochemical Tracers in Deep-Sea Corals from a Biomineralization Perspective
Get PDFDeep-sea corals have been developed as a useful archive of the chemistry and circulation of intermediate and deep waters in past oceans over the last three decades. However, applications of traditional paleoceanographic tracers in deep-sea corals remain a challenge due to our incomplete understanding of the biomineralization mechanisms underlying the incorporation of these tracers and their variabilities in the coral skeletons (a.k.a. the "vital effects"). In this thesis, an effort was made to understand the vital effects associated with the stable isotope as well as minor and trace element compositions of the aragonitic skeletons of the deep-sea coral species Desmophyllum dianthus, through a combination of empirical observations and a numerical model of coral calcification. Observations of the chemical and isotopic compositions of the coral skeletons were performed on four different spatial scales in a suite of modern D. dianthus specimens: bulk samples, micromilled samples, SIMS and nanoSIMS. These observations reveal tracer correlations in deep-sea corals that are coherent over different spatial scales and point toward a universal mechanism of the incorporation of these tracers through the biomineralization process. A few tracers emerge as promising proxies for the temperature (Li/Mg, Sr/Ca) and carbonate chemistry (U/Ca, B/Ca, Ba/Ca) of the oceans. The numerical model for coral calcification explains the strong δ18O and δ13C vital effects in individual deep-sea corals with an updated physicochemical basis, and carbonic anhydrase is found to play a key role in setting the slopes of the strong δ18O-δ13C correlations in different biogenic carbonates. The model also constrains the key physical parameters in the biomineralization process and is extended to explain the observed minor and trace element variabilities and correlations in deep-sea corals. The model can qualitatively explain the observed correlation patterns between Mg/Ca, Li/Ca, B/Ca and Sr/Ca in the coral skeletons, but quantitative data-model comparison is limited by both deficiencies in high-quality data and a lack of a well-constrained inorganic reference frame for aragonite. Future improvements in the geochemical tracers in biogenic carbonates will benefit from more extended empirical calibrations as well as a more complete mechanistic understanding of the key physicochemical and biological processes underlying the incorporation of tracers.</p
Kinetic and Spectroscopic Studies of Atmospheric Intermediates
Get PDFAtmospheric chemistry investigates the chemical transformations of atmospheric trace constituents through three complementary approaches: field observations, laboratory experiments, and computational modeling. This thesis used the laboratory experiment approach to explore persistent unknowns associated with free radical chemistry in the troposphere and stratosphere. Studies were conducted using two powerful techniques for the study of chemical kinetics: multiplexed synchrotron photoionization mass spectrometry and cavity ringdown spectroscopy.
In the first part of this thesis, we describe experiments measuring of the absolute photoionization cross sections of chlorine monoxide (ClO) and chlorine dioxide (ClOOCl). The cross sections of ClO were found to be at least a factor of three greater than a prior determination and those of ClOOCl were measured for the first time. ClO and ClOOCl play important roles in the catalytic destruction of polar stratospheric ozone and yet values of the parameters controlling the rate of atmospheric ClOOCl photolysis are uncertain. Our results show that photoionization spectroscopy is highly sensitive to the ClO radical and may be ideally suited for future experiments constraining the quantum yields of ClOOCl photolysis at wavelengths of relevance to the polar stratosphere.
We next discuss experiments investigating the kinetics of chlorine-substituted peroxy radicals (ClRO2). These species are formed in the troposphere upon oxidation of alkenes by chlorine atoms. We present rate constants for the formation and loss pathways of the simplest intermediate in this class: the β–chloroethyl peroxy radical. We also discuss measurements of the rate constants between NO and the ClRO2 formed upon oxidation of ethene, propene, 1-butene, 2-butene, 1,3-butadiene, and isoprene.
Finally, we present results exploring the impact of temperature and humidity on the chemistry of hydroxyl-substituted peroxy radicals (HORO2). In particular, the self reaction of the β–hydroxyethyl peroxy radical was investigated and found to be significantly enhanced by water vapor at cold temperatures. The product branching ratio was also studied and found to shift in favor of radical suppression. Given the prevalence of water vapor throughout the troposphere, altered reactivity of HORO2–H2O complexes likely plays an important role in atmospheric oxidation mechanisms.</p