VictorJuiz/thesis huggingface dataset:
Nucleic acid purification and analysis by isotachophoresis [electronic resource]
Keywords: Mechanical Engineering

Microfluidics has recently enabled new capabilities in life sciences research. By leveraging physics at the microscale, novel miniaturized methods and devices provide fundamental improvements over traditional assays including higher sensitivity, massive parallelization, speed and automation. For example, nucleic acid analyses such as PCR or capillary electrophoresis are now commonly executed on microfluidic platforms. However, extracting and isolating a set of molecules of interest from a biological sample remains a widespread challenge, in particular when the target is a nucleic acid; such sample preparation has been identified as the "weak link" of microfluidics. Moreover, the discovery of classes of small RNA such as microRNA (miRNA) has revealed the limitations of benchtop preparation methods. This work tackles these issues by leveraging an electrophoretic focusing method, isotachophoresis (ITP), to perform selective focusing of specific nucleic acid molecules contained in complex mixtures. This includes extraction of genomic DNA from blood and isolation of miRNA from total RNA. Also, we leverage the unique physics of ITP to perform simultaneous purification and analysis of these molecules, thus enabling automated analysis at unprecedented speed. ITP is a robust electrophoretic preconcentration technique which generates strong electric field gradients, and enables selective focusing and separation of charged species based on their electrophoretic mobilities. In this work, we show that we can extract and purify genomic DNA from chemically lysed whole blood samples by carefully controlling ITP electrolyte chemistry to achieve selective focusing of genetic material. We show that ITP outputs PCR-compatible DNA with high efficiency in about 1 min. This novel sample preparation technique allows for efficient, fast, and automated purification of DNA from 10 nL to 1 [Mu]L of biological fluids. We also demonstrate that ITP focusing of microRNA -- short (~22 nt), non-coding RNA regulating gene expression -- enables quantification and sequence specific detection. We leverage both the selective and preconcentration capability of ITP for the quantification of global miRNA abundance. This allows for the measurement of RNA silencing activity in specific cells or tissues. We have optimized ITP chemistry and used a multi-stage injection strategy to selectively preconcentrate and quantify RNA shorter than 40 nt. We discuss results of miRNA quantification for a wide variety of samples. Additionally, we show that the combination of selective ITP focusing with simultaneous hybridization with molecular beacons is an efficient method for detection and quantitation of specific miRNA sequences. We demonstrate the efficacy of this assay for the detection of a liver specific miRNA. Finally, we show that we can use ITP to perform polymerase chain reaction in isothermal conditions by creating a cycles of chemicals mimicking thermal cycling.
On ion probes and traps, barium tagging for the EXO double beta decay detector [electronic resource]
Keywords: Physics

The Enriched Xenon Observatory seeks to measure neutrino mass through observation of neutrinoless double beta decay. A new generation of ton-scale experiments are being developed, which aim to probe neutrinoless double beta decay half-lives on the order of 10^27 - 10^28 years. The keys to reaching these sensitivities are large source mass and reduction of radioactive backgrounds; this thesis details efforts to develop a system for tagging the 136-Ba+ daughter of the double beta decay of 136-Xe, for the purposes of background elimination in a large experiment.
On the emission of gamma rays by young pulsars [electronic resource]
Keywords: Physics

The gamma-ray emission from young rotation-powered pulsars has been studied in detail. The antenna patterns of emission are calculated for a variety of geometric emission models. These antenna patterns vary with magnetic inclination and spindown power; correspondingly, libraries of emission patterns are calculated across the phase space of possible parameter combinations. These libraries allow one to explore the possible gamma-ray light curves under a given model, for a given set of input parameters. A method of quantitative comparison was developed to allow the determination of a goodness-of-fit between an observed pulsar light curve and all of the possible simulated light curves for a given model. This method can localize the region of input parameter space that produces a model's best fit to an observed light curve. This can then be compared to external constraints on input parameters, often supplied by observations at other wavelengths (i.e., radio polarization and x-ray morphology). Finally, a simulation is run to reproduce the Galactic young pulsar population as faithfully as possible. Onto this population we apply the antenna patterns of various models in order to study the properties of the young gamma-ray pulsar population as a whole, constraining properties of the objects and evaluating the ability of the geometric gamma-ray models to reproduce the population-wide distributions of observables.
Optical microendoscopy for imaging cells lying deep within live tissue [electronic resource]
Keywords: Biophysics.

Optical microendoscopy is an emerging modality for imaging in live subjects. Using gradient refractive index (GRIN) microlenses, microendoscopy enables subcellular-resolution imaging in deep tissues that are inaccessible by traditional imaging techniques. We present a platform of methods and technologies that build upon GRIN microendoscopy: 1) miniaturized microscopes for imaging in awake, behaving animals, 2) methods for imaging contractile dynamics in the muscles of animal and human subjects, 3) chronic brain preparations that allow for longitudinal examinations of subcellular neuronal features and disease progression, and 4) novel microendoscope probes whose imaging capabilities approach that of standard water-immersion microscope objectives. When combined with the broad sets of available fluorescent reporters, and minimally invasive surgical preparations, the work described in this dissertation enables sophisticated experimental designs for probing how cellular char- acteristics may underlie or explain behavior, in models of both healthy and diseased states.
Optical techniques for integrated control and recording of neural activity [electronic resource]
Keywords: Bioengineering.

A long-standing objective of psychiatry has been the ability to both control and record the activity of precisely-defined populations of brain cells on the millisecond timescale most relevant for neural computation. Recent advances bring that goal increasingly near by leveraging the genetically-precise techniques of molecular biology with the high-speed, multiplexed command afforded by optical technologies to introduce and utilize light-sensitive neural activity control integrated with fast neural circuit imaging. In this thesis, I present exemplars of these technological advances and demonstrate their utility in illuminating the neural circuit basis of behaviors relevant to understanding psychiatric disease. I first show how fast neural circuit imaging may be integrated with optical neural control tools to develop insight into the role of genetically, developmentally, or projection defined populations of brain cells in mediating circuit-level physiological changes. I then demonstrate computational methods to analyze the resultant imaging data and apply fast circuit imaging to delineate links between hippocampal physiology and behavior in an animal model of depression. Finally, I present the development of a novel class of optically-activated, genetically-targetable control tools that permit optical control of G-protein coupled intracellular signaling; and the use of these molecular devices to determine causal roles of neuromodulatory inputs in reward processing. The development of these and similar optical modalities further improves the precision of questions addressable by the neuroscientist, and potentially the extent of disease treatable by the clinician.
Optimal controller synthesis for decentralized systems [electronic resource]
Keywords: Aeronautics and Astronautics

Optimal control theory can be classified, broadly speaking, as either centralized or decentralized. Centralized systems are generally thought of as a single decision maker, taking all sensor measurements and deciding all actuator inputs. By contrast, decentralized systems are typically characterized by multiple subsystems which each make decisions based on different sets of information. Optimal control, as the name suggests, is aimed at finding control policies which minimize a particular norm of the closed-loop map. For centralized problems, the only constraint on the set of admissible control policies is that the resulting system be internally stable. These types of problems have been solved for quite some time, and a variety of methods now exist to explicitly construct the optimal policies. Decentralization imposes additional constraints on admissible policies. These constraints can, in many cases, make the optimization problem intractable. Thus, for decentralized problems, our goal is two-fold. First, we try to identify classes of systems for which tractable representations of the optimization problem exist. Second, we need to synthesize the optimal decentralized controllers. This research is focused at decentralized problems which are represented by subsystems connected over graphs. The decentralization property is given as sparsity constraints on the admissible control policies. For such systems, there exists a simple condition which is sufficient for tractability of the optimization problem. For these systems, we provide a method for constructing the optimal decentralized controllers. These results provide significant insight into the structure of the optimal controllers. Moreover, they establish the state dimension of the optimal policies.
Optimization of organic solar cells [electronic resource]
Keywords: Electrical Engineering

Organic solar cell is a promising technology because the versatility of organic materials in terms of the tunability of their electrical and optical properties and because of their relative insensitivity to film imperfections which potentially allows for very low-cost high-throughput roll-to-roll processing. However, the power conversion efficiency of organic solar cell is still limited and needs to be improved to be competitive with grid parity. In this thesis, I'll discuss major factors to limit efficiencies of bilayer organic solar cells such as light absorption, exciton diffusion and open circuit voltage. Light trapping enhances light absorption and increases efficiencies with thinner devices structure. The technique is particularly important in organic solar cells because internal quantum efficiency of organic solar cells is low with thick films while absorption is weak with thin films. V-trap configuration is a simple and effective light trapping scheme for organic solar cells since there is no need to modify active layers, thinner films achieve high efficiencies and no tracking system is necessary. The effects of total internal reflection in shaped substrates and the comparison with shapes other than V-shape will be also provided in Chapter 2. Exciton diffusion is a main bottleneck in bilayer organic solar cells and thus the exciton diffusion length (LD) is an important parameter that determines efficiency. However, different groups report different LDs because there are many factors that affect the diffusion length or because there is a systematic error in the measurement Abstract v method. The photocurrent spectroscopy method to estimate LD in Chapter 3 and the effect of molecular packing on LD will be discussed in Chapter 4. Even when light absorption and exciton diffusion are optimized, the efficiency of a single junction organic solar cell is too low for commercial applications. Multijunction cells are a way to achieve the efficiencies needed. I'll discuss the practical efficiencies of tandem organic solar cells in the case of a series-connected tandem cell and an unconstrained (multi-terminal) tandem cell. In practical cases, unconstrained tandem cells result in higher efficiencies because of the increased freedom in choosing materials and device structures without requiring current matching. Semitransparent solid state dye sensitized cells are demonstrated as a route to realize three terminal tandem cells in Chapter 5. Curved focal plane arrays on stretchable silicon mesh networks can lead to realize high performance optical system with simple design. In Chapter 6, I show that curved focal plane arrays have optical advantages such as small number of elements, bright and accurate imaging for off-axis locations. Fabrication method is briefly introduced.
Optimizing the decision rule of a GPS integrity monitoring system for improved availability [electronic resource]
Keywords: Mechanical Engineering

The Global Positioning System, which was created by the United States Department of Defense specifically for guiding munitions, has disseminated into many applications of the present. Using a differential, ground based augmentation scheme has enabled GPS guidance to be used for the ultra-safety requisite use of landing aircraft. The civil incantation of this project is called LAAS, for Local Area Augmentation System. The military desired a comparable system for their use, and has instituted the JPALS program, for Joint Precision and Approach Landing System. The object is to deliver an integrity monitor to satisfy the stringent requirements of difficult military operation. Although the distinction of emphasis might seem to be on the inherent danger of physical conflict, since the landing platform is expected to be distant from any combat, it is actually the electro-magnetic conflict which takes precedence in this thesis. The JPALS land-based, or sea-based, Integrity Monitor must be designed to endure radio frequency interference, RFI. The potential of RFI to undermine the operation of a landing system is quite real. The intrinsic obligation of an Integrity Monitoring System is to bound the errors associated with the guidance being provided. To this end, the system must determine if any of measurements are faulty, and if those fault(s) indicate the presence of a potentially hazardous position error. Hardware and software can be used to mitigate the impact of radio frequency interference to a GPS based landing system. Beam-steering antennas can be used to emphasize the satellites' signals, and to simultaneously deemphasize a jamming source. The focus of this thesis is in the software algorithms. How can we enhance the performance of our system in its robustness to interference, by optimizing the decision rule it uses to exclude satellites, and receivers, thereby maximizing the amount of useable information, and minimizing the error limits that are broadcast to the approaching aircraft.
Option pricing and hedging with transaction costs [electronic resource]
Keywords: Statistics

The traditional Black-Scholes theory on pricing and hedging of European call options has long been criticized for its oversimplified and unrealistic model assumptions. This dissertation investigates several existing modifications and extensions of the Black-Scholes model and proposes new data-driven approaches to both option pricing and hedging for real data. The semiparametric pricing approach initially proposed by Lai and Wong (2004) provides a first attempt to bridge the gap between model and market option prices. However, its application to the S& P 500 futures options is not a success, when the original additive regression splines are used for the nonparametric part of the pricing formula. Having found a strong autocorrelation in the time-series of the Black-Scholes pricing residuals, we propose a lag-1 correction for the Black-Scholes price, which essentially is a time-series modeling of the nonparametric part in the semiparametric approach. This simple but efficient time-series approach gives an outstanding pricing performance for S& P 500 futures options, even compared with the commonly practiced and favored implied volatility approaches. A major type of approaches to option hedging with proportional transaction costs is based on singular stochastic control problems that seek an optimal balance between the cost and the risk of hedging an option. We propose a data-driven rule-based strategy to connect the theoretical approaches with real-world applications. Similar to the optimal strategies in theory, the rule-based strategy can be characterized by a pair of buy/sell boundaries and a no-transaction region in between. A two-stage iterative procedure is provided for tuning the boundaries to a long period of option data. Comparing the rule-based strategy with several other existing hedging strategies, we obtain favorable results in both the simulation studies and the empirical study using the S& P 500 futures and futures options. Making use of a reverting pattern of the S& P 500 futures price, we refine the rule-based strategy by allowing hedging suspension at large jumps in futures price.
Organometallic catalysis for controlled olefin polymerization and oligomerization [electronic resource]
Keywords: Chemistry

My Ph.D. work primarily involves the synthesis of ethylene-based oligomers and ethylene-styrene copolymers using organometallic catalysis. Chapter 1 reviews selective ethylene oligomerization that produces 1-hexene and 1-octene, with particular emphasis on the chromium-based catalytic systems and the mechanism by which they operate. Its application to the preparation of value-added chemicals is also covered. Chapter 2 and Chapter 3 present investigations on selective ethylene oligomerization with a Cr(PNP)Cl3/MAO catalyst system (PNP = Ph2PN(iPr)PPh2) in the presence of dialkyl zinc as an effective strategy for the co-generation of 1-octene and functionalized ethylene oligomers. Transmetallation with ZnMe2 during Cr-catalyzed ethylene tetramerization generated end-labeled 1-alkenes in Cn> 10 along with 1-octene, while that with ZnEt2 or ZnBu2 produced a mixture of end-labeled linear alkanes and 1-alkenes in Cn> 10 as well as 1-octene. Labeling studies with D2O provided a mechanistic test for metallacycle intermediates. Mechanistic proposals are presented to explain the formation of end-labeled products in the presence of various types of zinc alkyls. Chapter 4 and Chapter 5 examine a series of titanocenes [CpTiCl3, CpTiCl2TEMPO, CpNTiCl3, CpNTiCl2TEMPO, where Cp = C5H5, CpN = C5H4CH2CH2N(CH3)2, and TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl] for styrene homopolymerization and ethylene-styrene (ES) copolymerization at 70 °C and 120 °C to determine the influence of the pendant amine group and the hydroxylaminato ligand on comonomer incorporation and distribution. Titanocenes bearing the pendant amine ligand were active for ES copolymerization, whereas complexes lacking the pendant group afforded only mixtures of homopolymers, revealing the critical role of the pendant amine donor on the copolymerization behavior. At 120 °C, the titanocene complexes with the amine group generated high molecular weight ES copolymers along with an atactic polystyrene (aPS) byproduct. The molecular weight of the ES copolymers produced by a coordination mechanism was found to coincide with that of the aPS produced by a radical polymerization mechanism. A method to separate these two components was developed by the addition of a catalytic chain-transfer agent, cobalt tetraphenylporphyrin, successfully decreasing the molecular weight of the radically-produced aPS and offering expedient separation of the ES copolymer from the aPS. Chapter 6 describes a series of new mono-, bi-, and trimetallic complexes based on the dinucleating ligand, N, N'-bis[2-(diphenylphosphino)phenyl] formamidine (PNNP), which provides two binding sites suitable for accommodating Pd, Ni, Co, Fe, and Cu. Definitive evidence for the structures of all complexes were given by X-ray crystal structures. The synthesis, characterization and crystal structure of each complex are discussed.
Oscillations, waves, and symmetry breaking in cell motility [electronic resource]
Keywords: Biochemistry

Actin-based cell migration depends on the temporal and spatial integration of multiple force-generating systems. Polymerization of the actin network drives protrusion of the cell membrane, and the stretched membrane, in turn, exerts force on the actin network. Myosin contraction of the viscoelastic actin network is balanced by cell-substrate adhesion. The molecular components that contribute to each of these forces - actin-based protrusion, membrane tension, myosin-mediated contraction, and adhesion - have been extensively characterized, but the manner in which they are integrated in vivo to give rise to large-scale emergent properties such as cell shape and movement is not well understood. This thesis describes the role of cell-substrate adhesion in large-scale actin network organization and dynamic cell shape determination. Keratocytes exhibit several non-steady-state behaviors, including oscillatory retraction of the trailing edge, waves of protrusion at the leading edge, and symmetry breaking and motility initiation. I have shown that the mechanical and biochemical properties of adhesions contribute to each of these dynamic behaviors. Oscillatory retraction of the trailing edge emerges in fast-moving, fan-shaped keratocytes and I present evidence consistent with a mechanical model in which elastic coupling between the front of the cell and adhesions in the rear drives oscillations. In contrast, I have found that protrusion waves at the leading edge are likely the result of the biochemical, rather than mechanical, properties of adhesions. Traveling waves emerge at high adhesion strengths and adhesion maturation is required for waving. Mature adhesions have been shown previously to bind several components that contribute to leading edge protrusion, including VASP, a protein that promotes actin polymerization by preventing barbed end capping. Dynamic localization of VASP to the leading edge in waving keratocytes is consistent with a reaction-diffusion model in which global depletion of VASP by mature adhesion, in conjunction with local depletion by the polymerizing actin network, results in lateral propagation of protrusion waves. Finally, I present evidence that suggests that balance between cell-substrate adhesion and myosin contraction sets the mechanical instability threshold above which stationary, radially symmetric keratocytes break symmetry and begin to move. On the whole, the work described here represents significant progress towards elucidating the self-organization principles that underly whole cell migration.