VictorJuiz/thesis huggingface dataset:
New techniques for precision atom interferometry and applications to fundamental tests of gravity and of quantum mechanics [electronic resource]
Keywords: Physics.

Light-pulse atom interferometry--in which quantum mechanical atomic wave packets are split along two paths and later recombined and made to interfere by sequences of optical pulses--is a remarkably sensitive technique for measuring inertial forces, allowing it to be a valuable tool for applications ranging from fundamental tests of gravity to geodesy and inertial navigation. The inertial sensitivity of an atom interferometer is proportional to its enclosed spacetime area--that is, the product of the spatial separation between the two interferometer paths and the interferometer duration. Therefore, new techniques that allow this spacetime area to be increased are essential in order for atom interferometry to reach its full potential. In this thesis, I describe the development of such techniques. We approach the problem of increasing the interferometer spacetime area on two fronts. First, we implement new methods to increase the momentum transferred by the beam splitters of the interferometer. The velocity difference and therefore the spatial separation of the interferometer paths are proportional to this momentum transfer. Conventional atom optics techniques involve beam splitters that transfer two photon momentum recoils (2 hbar k) to the atoms. I will discuss our realization of large momentum transfer (LMT) beam splitters that transfer up to 100 hbar k. Second, we have built a 10 m tall atomic fountain that allows the total interferometer duration to be increased to 2 s. Ultimately, we combined LMT atom optics with long-duration atom interferometry in the 10 m atomic fountain, leading to very large spacetime area atom interferometers. In these very large area atom interferometers, the separation between the two atomic wave packets that respectively travel along the two interferometer paths reaches distances of up to 54 cm. Therefore, in addition to offering greatly increased inertial sensitivity, these interferometers probe the quantum mechanical wavelike nature of matter in a new macroscopic regime. I will discuss the techniques we devised to overcome the many technical challenges associated with such interferometers, which in other apparatus have prevented interference from being maintained for path separations larger than 1 cm. I will also describe initial results from the use of our very large area interferometers to test the equivalence principle with Rb-85 and Rb-87 and our plans for further progress in this direction. Very large area atom interferometry requires high laser power and extremely cold atom sources. We have developed a novel high power, frequency doubled laser source at 780 nm that is suitable for atom optics. Also, we have implemented a sequence of matter wave lenses to prepare and measure atomic ensembles with record-low effective temperatures of 50 pK. In addition to applications in atom interferometry, we expect that such an atom source will be broadly useful for a wide range of experiments.
Nitrogenous disinfection byproducts [electronic resource] : identifying formation pathways and developing engineering controls in impaired and recycled water
Keywords: Civil and Environmental Engineering.

Disinfection of potable water is one of the great public health victories of the twentieth century, responsible for the avoidance of millions of deaths due to waterborne illness. However, application of disinfectants, typically chemical oxidants, leads to formation of hundreds of trace contaminants, often carcinogens, and consumption of chlorinated water has been epidemiologically linked to bladder cancer and certain birth defects. Eleven of these compounds are federally regulated in drinking water, but certain non-regulated disinfection byproducts (DBPs) are orders of magnitude more toxic than currently regulated compounds. Two specific DBPs, chloropicrin and N-nitrosodimethylamine (NDMA), are especially genotoxic, and are associated with nitrogen input into drinking water supplies. Wastewater-impacted drinking water and recycled wastewater are enriched in the precursors of these compounds, and their formation during potable water treatment is likely to grow, as wastewater increasingly contributes to the water supply. This thesis focuses on applying the tools of environmental organic chemistry to identify the chemical precursors and formation mechanisms of these compounds, leading to strategies for their control during water treatment. In particular, ozonation of primary and secondary amine compounds, leading to formation of nitro compound intermediates, was found be responsible for chloropicrin formation during water treatment. Secondary N-methylamines and primary amines geminal to facile leaving groups were particularly potent precursors, forming chloropicrin at up to 50% yield when exposed to ozone followed by chlorine. Based on this predominant formation pathway, chloropicrin precursors may be oxidized upstream of ozone addition to prevent chloropicrin formation. Strategies for controlling NDMA formation, a major concern during wastewater recycling, were developed based on an understanding of the chemical composition of NDMA precursors, and chloramines, the primary disinfectant applied during wastewater reuse. Minor modifications to wastewater recycling operations, in particular switching from low-pressure to medium-pressure mercury lamps for ultraviolet light treatment, and minor adjustments in the application of chloramines, were shown to dramatically reduce NDMA concentrations in final effluent. Finally, the effluent from a new, all-anaerobic wastewater treatment system was demonstrated to more efficiently remove trace contaminants and DBP precursors than conventional aerobic treatment, suggesting that this energy-saving technology may also be more suitable for water reuse than conventional treatment. These findings facilitate reducing the chronic health risk associated with consumption of (intentionally or unintentionally) recycled wastewater.
Non-cell autonomous effects in diffuse intrinsic pontine glioma
Keywords:  Department of Biology
pediatric high grade glioma
diffuse intrinsic pontine glioma
DIPG
SPARCL1
tumor microenvironment
Thesis

Diffuse intrinsic pontine gliomas (DIPG) are highly aggressive tumors originating in the pons of the brainstem during childhood. With an average survival post-diagnosis of only 9 months, DIPG is the leading cause of pediatric brain tumor death. Because the unique biology underlying the disease is not well understood, little progress has been achieved in treating DIPG in the past thirty years. Here, we demonstrate that DIPG cells secrete soluble factors that promote abnormal proliferation of surrounding neural precursor cells. Using a combination of biochemical techniques, we identified SPARCL1 as a protein secreted by DIPG cells in vitro that is sufficient to increase both NPC and DIPG growth. Currently, therapeutic interventions mainly focus on targeting cancer cells themselves. However, we postulate that DIPG cells incorporate healthy neural precursor cells into the tumor mass. Thus, targeting interactions between DIPG cells and NPCs in the developing brain holds the potential to slow DIPG progression.
Nonlinear optical devices as single-photon quantum frequency converters [electronic resource]
Keywords: Electrical Engineering.

Appropriate interfaces between quantum nodes and low-loss quantum channels in long-distance quantum communication networks and upconversion-assisted SPDs are based on quantum frequency conversion (QFC) processes. QFC processes give us the ability to translate the qubit's carrier frequency while its quantum state is maintained. The primary interest of QFC has been upconversion single-photon detection. A process where a single-photon level signal in the telecommunications band is upconverted to a visible wavelength and use the well-developed single-photon detectors based on silicon avalanche photodiodes. The need for an interface between coherently controlled matter qubits (which typically have optical transitions in the visible or near-infrared spectral range) and low-loss photonic quantum channels (at the 1.3 or 1.5 m bands in silica optical fibers) is a primary challenge toward developing a long-distance hybrid quantum network. The possibility of making such an interface based on nonlinear interactions is another motivation to develop QFC processes. We can reach high conversion efficiency by using reverse-proton-exchange waveguides. A key issue in these devices is minimizing the generation of noise photons in the signal band by inelastic scattering of the pump. The two primary origins for this noise processes are known as spontaneous parametric down conversion (SPDC) and spontaneous Raman scattering (SRS). It has been shown that long-wavelength-pumping dramatically reduce the dark-count rate. This requirement limits the wavelength-translation range which can be achieved in a single conversion step. This constraint led to the development of integrated devices based on two cascaded parametric conversion processes. We discuss considerations in using cascaded frequency mixers for low-noise quantum frequency conversion between two widely disparate frequencies, such as long-wavelength-pumped down-conversion of visible single photons from a diamond nitrogen-vacancy center or trapped ion to 1550 nm. We have demonstrated an integrated architecture for low-noise, low power cascaded quantum frequency conversion from 649.7 nm to 1595 nm. The results presented in this dissertation represent a critical step toward low-power, low-noise quantum frequency conversion for long distance quantum communication networks.
Nonlinearities in bulk acoustic mode silicon micromechanical resonators [electronic resource]
Keywords: Mechanical Engineering.

Capacitive microelectromechanical (MEMS) oscillators represent a promising alternative to quartz-based systems as they provide benefits such as mass fabrication, size reduction, and compatibility with CMOS IC integration. However, one drawback that comes with size reduction is smaller induced currents, which leads to increased noise in the oscillator output. To overcome this challenge, resonators have to be driven to larger amplitudes of motion, and oftentimes operate in the nonlinear regime, where the resonator dynamics become much more complicated (e.g. Duffing-type nonlinearity, nonlinear damping, etc.). This work aims to characterize the nonlinear behavior in commonly used bulk acoustic mode resonators fabricated in a modified epi-seal process, where a variety of devices with reduced design limitations can be fabricated in this process while maintaining the core epi-seal process features (e.g. high stability, reliability, ultra-clean, etc.). Utilizing this process, high quality factor devices without release etch-hole in the device layer can be fabricated (e.g. Lamé resonator operated at 10.1 MHz with quality factor of 2.27e+13), which is beneficial towards characterization of nonlinear behavior in bulk mode devices. Frequency stability experiments have also been performed, with the measured stability of ± 18 ppb over one month of testing. Cavity pressure studies indicate a cavity pressure of less than 0.1Pa equivalent of air. These results justify that the modified process is comparable with the standard epi-seal process. The effect of doping on material nonlinearities is also analyzed, where three types of bulk acoustic mode resonators are used to characterize device nonlinearity with respect to doping type/concentration and orientation. Measurements on the effect of electrostatic nonlinearity are performed to justify that these devices are dominated by material nonlinearity. While recent studies have demonstrated the use of heavily p- or n-type doping for passive frequency-temperature compensation, this work demonstrates that device nonlinearity is also heavily influenced by the resonator mode shape, device crystal orientation, doping type and concentration. Lastly, a few modal coupling behaviors observed in commonly used bulk-mode resonators will be introduced, where we demonstrate that certain design parameters can be used to tune the modal coupling strength, thus directly affecting the resonator's frequency and quality factor.
Not isolated, but still insulated [electronic resource] : switch-like transitions modularize biological networks
Keywords: Biology.

Cellular decisions are outputs of computations performed by complex genetic networks of interconnected protein, RNA, and DNA sequence elements that are difficult to comprehensively analyze. One way to study the principles underlying these computations has been to examine the dynamics of smaller sub-networks, known as network motifs. However, it is not clear whether this is valid because these motifs are embedded in complex larger networks. Here, we explore the conditions for modularity and the bounds of validity of motif analysis in the context of a feedforward motif in the S.cerevisiae network comprising G1/S cell cycle and pheromone pathways. Using modeling and single cell analysis, we find that the feedforward motif accurately predicts the dynamics of the cell cycle inhibitor Far1 because it is insulated from the effects of gradually increasing cell cycle inputs by a positive feedback-driven switch. Before the cell cycle switch, the cell cycle signal has no effect on Far1, so feedforward motif predicts the network behavior. Conversely, after the switch, the feedforward motif is dismantled and has no effect on cell cycle dynamics. When this insulation is broken, the network is no longer modular and the feedforward motif no longer predictive. Thus, switch-like elements can digitize analog signals to modularize complex networks so that smaller sub-networks function in effective isolation and can be analyzed using motif analysis. This work demonstrates how, despite the interconnectivity of networks, motifs can be insulated by switches that produce well-defined cellular states.
[Not] lost in translation [electronic resource] : optogenetic and chemogenetic control of sensory circuits
Keywords: Bioengineering.

This dissertation has two purposes: 1. To increase our ability to control the neural circuits that control pain perception, ideally in a way that can be applied to treat people with chronic pain disorders. 2. To improve our understanding of the spinal circuits required to process mechanical, thermal, and itch-related stimuli. Towards these ends, we performed three primary studies: 1. We initially asked whether optogenetic techniques (at the time used primarily in the brain) could be used to control peripheral pain circuits. We developed viral methods to specifically express stimulatory and inhibitory opsins in unmyelinated primary afferent neurons, and characterized the resulting transduction profile. We found that transdermal illumination could be used to non-invasively stimulate or inhibit pain perception. While blue light resulted in marked pain-related behavior in mice expressing channelrhodopsin-2 (ChR2), yellow light resulted in effective pain-suppression in mice expressing halorhodopsin (NpHR). Importantly pain inhibition could be maintained in mouse models of neuropathic pain --- pain thresholds under illumination could be restored to pre-injury levels. In a follow-up to this study, we found that optogenetically evoked pain-responses could be used to analyze analgesic drug efficacy. 2. In a second study, we addressed a major limitation of the first study --- that it enabled optogenetic inhibition of pain only through constant illumination, a major translational limitation. We devised two complementary strategies for sustained inhibition of pain perception over hour-long periods. In the first, we exploited innovations in opsin engineering to show that the step-function inhibitory channelrhodopsin (SwiChR), if expressed in primary afferent nociceptors, enabled long-term inhibition of pain perception with temporally sparse illumination. In the second, we expressed the inhibitory Gi coupled hM4D receptor in primary afferent neurons, and showed that activation of this designer receptor (DREADD) resulted in significant inhibition of pain thresholds. 3. Finally, we exploited innovations in light-delivery systems for optogenetic control of the spinal cord to examine the role of an excitatory interneuron population (somatostatin+ neurons) in mediating sensory perception. Using a combination of optogenetics, chemogenetics, and anatomical tracing, we examined the consequences of reversible bidirectional control over somatostatin+ interneurons, and identified a novel interaction between somatostatin+ neuron activity and itch-related behavior.
Notch3 signaling and pericyte proliferation in coronary artery maturation
Keywords:  Department of Biology
Biology
Developmental Biology
Pericytes
Coronary Arteries
Notch3
Proliferation
Thesis

More than seven million people die from coronary artery disease each year, making it the leading cause of death worldwide. Investigating the developmental origins of coronary arteries can lead to a better understanding of and improved therapeutics for coronary artery disease. Many aspects of coronary artery angiogenesis, however, remain unclear. Pericytes, mural cells closely associated with small blood vessels, have recently been identified as progenitors for coronary artery smooth muscle cells (caSMCs) (Volz et al., 2015). This pathway is in part controlled by Platelet Derived Growth Factor Receptor β (PDGFRβ), an important receptor for smooth muscle development that diminishes caSMC maturation upon deletion (Mellgren et al., 2008). Similarly, studies of the Notch3 receptor have shown that notch3 is involved in pericyte development and maintenance and promotes vascular smooth muscle cell proliferation (Greenwald, 1998). Our study analyzes the effects of the Notch3 receptor on the development of coronary artery smooth muscle in a murine model. Coronary artery smooth muscle develops when blood flow induces vessels within the vascular plexus, an immature vessel bed permeating the entire ventricular heart muscle, to remodel into mature coronary arteries with smooth muscle cell coating in regions called remodeling zones (Red-Horse et al., 2010; Kattan et al., 2004). Here, we show that the deletion of Notch3 disrupts caSMC differentiation at the coronary artery remodeling zone. The defect in smooth muscle, however, is likely not due to differential proliferation of pericytes between wild type and Notch3-null mice. We additionally characterize pericyte biology at sites of arterial differentiation and show that the remodeling zone contains significantly more pericytes than the vascular plexus, but there is no difference in proliferation at the former site. These data collectively indicate that pericytes give rise to coronary artery smooth muscle through an integral Notch signaling mechanism and that smooth muscle differentiation involves pericytes migrating into the remodeling zone rather than increased proliferation at the remodeling zone. This reveals a new potential pathway that can be therapeutically targeted during coronary artery disease.
Not-quite-optimal market design [electronic resource]
Keywords: Management Science and Engineering.

This thesis contains two self-contained essays on market design. The first essay considers a many-to-one matching setting in which students list a limited number of schools as acceptable, and matches are formed using the deferred acceptance algorithm. I provide exact asymptotic expressions for the number of students receiving a top-k choice as a function of factors such as the number of students, the number and capacities of schools, the length of student lists, the correlation in student preferences, and the procedure for generating school priorities. I then compare outcomes across priority rules, and find that there is a tradeoff between the goals of assigning many students to their top choice, and leaving few students unassigned. For example, when comparing district-wide and school-specific lotteries, the former assigns more students to their first choice, while the latter assigns more students overall. The second essay considers a setting in which several advertisers compete in an auction for the right to place an ad. Each advertiser has a value that is the product of the "common value" of the impression and an advertiser-specific idiosyncratic "match value." Although most advertisers observe their value for the impression, one advertiser is unable to do so. The first result is that holding a second price auction for the impression may lose up to half of the available match value. Meanwhile, the optimal auction induces adverse selection and is susceptible to shill bidding. I introduce Modified Second Bid auctions as the only deterministic anonymous mechanisms that are fully strategy-proof and eliminate adverse selection. Furthermore, when match values are independent draws from a power law distribution, a Modified Second Bid auction captures at least 94.8% of the value generated by the optimal mechanism.
Novel Role of Wnt Target Receptors in Cartilage Development
Keywords:  Department of Biology
Biology
Chondrogenesis
Cartilage
Differentiation
Wnt Pathway
Thesis

Articular cartilage, a smooth white tissue composed of chondrocytes, cushions the ends of joints, yet possesses very poor regenerative potential. Identifying novel factors that govern cartilage development is an essential foundation for developing stem and progenitor cell-based therapies. Such therapies could include using cartilage regeneration to address focal cartilage injuries as well as osteoarthritis, a debilitating disease brought about by loss of cartilage tissue. Previous work has elucidated the role of the Wnt signaling pathway, a key regulator of gene transcription, in the process of chondrogenesis, or cartilage differentiation. We seek to address the specific role of one of the pathway’s non-canonical receptors: the leucine-rich repeat-containing G-protein coupled receptor (Lgr). The specific member Lgr5 was chosen as the focus of our study because of its previous implication as an adult stem cell marker. This trait is of particular interest to us in the field of progenitor cell-based therapies for cartilage tissue. We sought to investigate the expression and role of Lgr5 in cartilage in order to understand and identify tissue-resident stem or progenitor cells in the tissue. Surprisingly, we found that Lgr5 expression increased during chondrogenesis, and its knockdown significantly impaired this process. Using global microarray-based gene and protein expression assays to analyze the chondroprogenitor cell line ATDC5, we found that the Lgr5 knockdown led to decreased expression of the known chondrogenic markers Type II Collagen (Col2a1) and Aggrecan (Agc). Additionally, we observe that Wnt3a dependent β-catenin is activated during chondroprogenitor differentiation in parallel to Lgr5 upregulation. Further research towards understanding the molecular mechanisms underlying cartilage differentiation will aid in unlocking the tissue’s regenerative potential and help define future clinical strategies for enhancing cartilage regeneration.