VictorJuiz/thesis huggingface dataset:
Defining and detecting meniscal heterogeneity [electronic resource] : implications on treatment and diagnosis of osteoarthritis
Keywords: Bioengineering.

Meniscal degeneration often precedes cartilage degeneration, and effective detection and treatment can be critical in preventing osteoarthritis. The meniscus is a heterogeneous tissue, and obtaining information on the varying characteristics of meniscal regions is important in investigating such strategies. However, no current method exists that can detect such meniscal heterogeneity in the tissue matrix. In addition, the lack of quantitative information on meniscal heterogeneity hinders the development an effective, long-term solution that can treat degeneration in the meniscus. The purpose of this dissertation was thus 1) to find quantitative characteristics that defined meniscal heterogeneity and 2) to evaluate non-invasive diagnostic methods that could reflect the matrix tissue properties and detect meniscal heterogeneity. To accomplish the first goal, gene expression profiles of meniscal cells were statistically analyzed to identify quantitative markers that could distinguish between different regions of the meniscus, describing its heterogeneous properties. This information was then used to evaluate cell sources for meniscal tissue engineering, demonstrating the potential application of these quantitative markers in developing an effective treatment for meniscal degeneration. Secondly, in order to detect meniscal heterogeneity, which is reflected in the changing tissue properties within the tissue, magnetic resonance imaging was used. The potential of the imaging parameters T1[rho] and T2 relaxation times in detecting various meniscal tissue properties, including the matrix composition and mechanical properties, was examined. Ultimately, such information would be useful in identifying internal degenerative changes that take place in the matrix of the tissue prior to macroscopic injuries. In this study, both T1[rho] and T2 relaxation times showed variation with tissue properties but were highly correlated with one another, indicating that only one imaging parameter might be necessary as a diagnostic tool in a clinical setting. In addition, an exploratory aim visualized the internal secondary collagen network in the meniscus and examined its deformation in different mechanical loading positions. This work significantly adds to the understanding of the heterogeneous properties of the meniscus and the potential of magnetic resonance imaging parameters as detection markers. It contributes to the advancement of diagnosis and treatment strategies for meniscal degeneration, which has further implications for preventing osteoarthritis progression.
Degenerate ultra-broadband opos for mid-infrared frequency comb generation [electronic resource]
Keywords: Electrical Engineering.

This thesis consolidates an extensive study of optical parametric oscillators (OPOs) optimized for generating extremely broad bandwidth output in the mid-infrared (mid-IR). Optical parametric oscillation is a well-known frequency conversion technique employing an optical element with significant second order nonlinear susceptibility, situated in an appropriate resonator, to convert a shorter wavelength pump laser to longer wavelength OPO outputs. However, our technique is distinct in its optimization for simultaneous oscillation over an extremely broad bandwidth. This is accomplished with a doubly-resonant design, operated at or near degeneracy in a low-dispersion resonator containing a bandwidth-optimized non-linear element and pumped by a mode-locked near-infrared fiber laser. Such an OPO is suitable for generating spectrally and spatially bright, broadband phase- and frequency-locked combs in the absorption-rich mid-IR 'molecular fingerprint' region. Our synchronously pumped system architecture is readily applied to systems operating at other center wavelengths and repetition rates. The comparative simplicity allows new instruments to be envisioned, and is expected to be of great practical interest. Several sync-pumped OPO systems were studied, the first of which are based on periodically poled lithium niobate (PPLN) and pumped by commercial ultrafast erbium fiber lasers at 1.55 µm. With an Er/PPLN OPO system we obtained a pump threshold of 9 mW, output power of 60 mW, and 20dB bandwidth extending from 2.5 to 3.8 µm. Through collaboration, we benefitted from custom orientation patterned gallium arsenide (OP-GaAs) and state-of-the-art femtosecond thulium fiber lasers at 2.0 µm. These components allow us to operate sync-pumped OPOs producing more than 35-mW of output power, 30dB bandwidths extending from 2.6 to 6.1 µm, and pump thresholds of less than 20mW. The broad mid-infrared spectral bands addressed by these sources, combined with the underlying comb structure, make them uniquely suitable for advanced spectroscopic techniques, including "dual-comb" FTIR spectrometry. We have demonstrated the utility and versatility of these OPO sources for sensitive intracavity spectroscopy, remote, and micro-scale spectral absorption measurements.
Degradation of cartilage and meniscus tissues [electronic resource] : an in vitro investigation in osteoarthritis development
Keywords: Mechanical Engineering.

Osteoarthritis is a debilitating disease that affects 27 million Americans. Major risk factors for osteoarthritis include mechanical injury and obesity. Prolonged exposure to mechanical overload in the knee joint, either by injury, malalignment, or obesity, is associated with early onset of osteoarthritis. Recent evidence demonstrates that adipose tissue is a metabolically active and produces systemic biofactors known as adipokines associated with numerous diseases including cardiovascular disease, hypertension, insulin resistance, rheumatoid arthritis, and osteoarthritis. Interestingly, obesity is a significant risk factor for hand osteoarthritis, suggesting a biologic link between obesity and osteoarthritis that is perhaps mediated through adipokines. While many studies investigating in vitro osteoarthritic degradation have focused on cartilage tissue, the menisci has received relatively little attention despite it's important functional role in joint stability and load transfer in the knee. The purpose of this thesis was to explore the relative susceptibility of cartilage and meniscal tissue degradation to in vitro mechanical overload and adipokine exposure using an immature bovine tissue explant model. To explore the injury response, explants of cartilage and meniscal tissues were compressed at various strain rates to create a spectrum of peak injury forces and cultured for up to nine days post-injury. To investigate whether adipose tissue and adipokines can biochemically induce changes in cartilage and meniscal tissues, explants of cartilage and meniscal tissue were incubated with infrapatellar fat pad or individual adipokines and assessed for altered matrix metabolism. Overall, results indicate that, while mechanically robust, meniscal tissue is vulnerable to biologic damage induced by mechanical overload and adipokines. We also demonstrate for the first time that meniscal tissue is more catabolically sensitive to adipokines than cartilage tissue. These results provide evidence that obesity-driven degradation of knee joint could be biochemically mediated and suggest meniscal degradation as a possible early event in osteoarthritis development.
Derivative-free optimization for generalized oil field development [electronic resource]
Keywords: Energy Resources Engineering.

Given the substantial costs and potential rewards associated with petroleum field development and reservoir management, it is essential that these operations be performed as close to optimally as possible. This work presents numerical methods for field development optimization where the goal is to simultaneously determine the optimal number and type of new wells, the sequence in which they should be drilled, as well as their corresponding locations and (time-varying) controls. The optimization is posed as a mixed-integer nonlinear programming (MINLP) problem and involves categorical, integer-valued, and real-valued variables. The formulation handles bound, linear, and nonlinear constraints; the latter are treated using filter-based techniques. Noninvasive derivative-free approaches are applied for the optimizations. Methods considered include Mesh Adaptive Direct Search (MADS, a local pattern search method), Particle Swarm Optimization (PSO, a heuristic global search method) and a PSO-MADS hybrid. Single and biobjective optimization example cases are presented. These cases involve well control optimization, joint well placement and control, and generalized full-field development problems. Significant improvement over base-case field development plans is demonstrated in all cases and the PSO-MADS hybrid procedure is shown to outperform its component methods. It is concluded that, although demanding in terms of computation, the methodology presented here is applicable for realistic petroleum field development and reservoir management.
Design and development of a 1mm resolution clinical positron emission tomography (PET) system [electronic resource]
Keywords: Electrical Engineering.

Positron Emission Tomography (PET) is an in-vivo medical imaging modality that extracts information about molecular processes associated with disease. A PET system produces an image of radiopharmaceuticals that have preferentially accumulated in certain cells of tissues in the body, such as cancerous lesions. Clinical PET systems have about 5-10mm spatial resolution, and thus have difficulty resolving very small lesions. So, improving the resolution of PET is an active area of research. This thesis describes the design of a 1mm resolution PET system for breast cancer imaging and the strategies used to overcome the challenges of developing such a high resolution PET system. The detectors in this PET system consist of lutetium yttrium oxyorthosilicate (LYSO) scintillation crystal arrays coupled to position-sensitive avalanche photodiodes (PSAPDs). There will be over 2000 Dual-LYSO-PSAPD detector modules in the final system, each requiring a bias voltage of 1750 Volts. A programmable high voltage distribution method allows the bias voltage to be optimized for each detector module. Multiplexing of detector signals reduced the number of interconnects by 40% and front-end electronic channels by 33%. Charge division and charge sharing signal conditioning compensate for the mismatch between the detector signal and the front-end electronics input dynamic range, as well as for parasitic capacitance introduced by interconnect. A model of the detectors and electronics was created to help understand the system and to assist in the system design process. Two cartridges of the system, consisting of 256 Dual-LYSO-PSAPD detectors, were constructed and characterized. The system energy resolution was 11% FWHM (full-width-at-half-maximum) and the measured spatial resolution was less than 1mm. The system was able to produce reconstructed images of a phantom with 1.2mm rods filled with a solution of the positron emitter Fluorine-18.
Design of Online Peer-to-Peer Investment Platform Offering Incentive-Compatible Revenue-Sharing Innovation
Keywords:  Department of Economics
Stanford Department of Economics
rural credit market
Thailand
Thesis

Motivated by my 2010 field investigation of the rural credit market in Thailand, which revealed the appalling extent to which low-income entrepreneurial-minded population are underserved by existing capital-providing sources, including formal financial institutions and the microfinance movement, I conducted further exploration of alternative funding models, such as online-social lending organizations, as well as assessment of innovative financial products, in the hope of identifying novel micro-funding model capable of providing better financial inclusion for a group of financially underserved population at the base of the economic pyramid, representing 3 billion of the world’s population. With main characteristics of the potential platform in mind, I design a novel online peer-to-peer social investment platform, offering incentive-compatible revenue-sharing product, which solves many of the problems inherent in the developing world’s credit markets. This financial product exhibits the beneficial features of a quasi-equity financing scheme, while overcoming the implementation challenges that have prevented widespread adoption of quasi-equity financing instruments in MFIs for many decades. The business plan for the platform is illustrated in one main section of this paper, while another section features indepth analysis of the revenue-sharing model and complementary mechanisms used to align Investor-Client incentives and alleviate informational asymmetry problems.
Design of versatile telerobotic systems using variable impedance actuation and control [electronic resource]
Keywords: Mechanical Engineering.

Telerobotic systems allow a human operator to remotely manipulate an environment. Using telerobotics, we can remain distant from dangerous or difficult-to-reach locations, or scale our motions and forces to levels beyond normal human abilities. We would like these systems to be capable of the widest possible range of actions, from delicate and gentle to strong and firm, making them more capable tools in the remote environment. Human versatility, in part, comes from our ability to adjust impedance to suit the task we are performing. Humans accomplish this by flexing and relaxing muscles, reorienting the skeletal structure, bracing on nearby objects, and through sensory feedback. In a telerobotic system, the impedance is a combination of the robot impedance, the controllers, position and force scaling, and the human impedance. This multiplicity of contributions limits the operator's ability to affect the overall system behavior directly, ultimately limiting the system's potential abilities. In this research, I have worked to extend the range of telerobotic performance capabilities by incorporating variable impedance actuators and control into the telerobotic system. Their inclusion gives the operator a more direct ability to control the telerobotic impedance and lessens the need for high-bandwidth, transparent controllers. This ultimately lets the operator perform a wider range of tasks. Additionally, the system performance becomes less sensitive to factors such as force feedback level and time delay. In this thesis, I investigate accomplishing impedance control for telemanipulation using variable stiffness actuators and software impedance control. I discuss the need for variable hardware actuators to control short-duration interactions, such as impacts. Based on insights from this work, I design several variable impedance telerobotic control architectures for improved manipulation performance. Results are presented from experiments in one-DOF and multi-DOF, as well as a user study, confirming improved versatile performance and reduced sensitivity to force feedback level. It is my hope that this work will help encourage a design perspective for telerobotic systems which emphasizes the system's versatility and usability over the goal of pure transparency.
Designing automated systems for sample preparation of nucleic acids using isotachophoresis [electronic resource]
Keywords: Chemical Engineering.

Purified DNA serves as a template for a wide array of analysis techniques, ranging from sequencing to PCR and hybridization assays. DNA analysis can be used for clinical diagnosis, for forensic investigation, and for a range of research purposes. These analysis techniques improve each year, but they are all constrained by the availability of purified DNA. DNA is typically derived from raw biological samples that contain a host of other molecular species, including proteins, lipids and metal ions. These species can inhibit analysis of the DNA, so purification of DNA from complex sample matrices is a necessary precursor to analysis. Typically, DNA purification is performed using either liquid-liquid extraction or solid-phase extraction, both of which require manual labor, involve toxic chemicals, and are difficult to miniaturize. Isotachophoresis (ITP) is an alternative method for DNA purification that does not rely on specialized surface chemistry or toxic chemical species. Instead, ITP uses electric fields to selectively pre-concentrate DNA from a raw sample, and simultaneously separate it from inhibiting species. ITP purification of DNA has been demonstrated from human serum, plasma, and whole blood, and the same technique has been used to purify RNA from bacteria in human blood and urine. Until recently, the parameters governing extraction efficiency, throughput, and separation quality in ITP purification were not well established. This thesis is focused on rational analysis for designing and optimizing ITP systems for rapid, high quality DNA purification.
Designing life [electronic resource] : studies of emerging adult development
Keywords: Education.

Emerging adulthood often includes a number of important transitions, moving out of the parental home, and transitioning from life as a student to work. Much research on this period of life focuses on work development; however, the present studies instead focus on self-development more broadly. In order to understand such development, these studies are integrated with a course on life design. Three methodologies are brought to bear, a survey study drawing on measures of well being and goals examining participants and non-participants, an interview study focusing on emerging adults conceptions of morality, and an observational and repeated interview study examining course activities and course participants experiences of and reflections on those activities. These studies demonstrate the relevance of the course to increases in life meaningfulness, personal growth, life decision-making, and moral formation. They also serve to demonstrate new models of goal development and moral development. These findings are then interepreted as they illuminate meaning and emerging adult development.
Detection of multiple change-points [electronic resource] : sequential testing and model selection
Keywords: Statistics.

In this thesis, we consider the problem of estimating the number of change-points and their locations in a process. In the first part of the thesis, we focus on a sequence of non Gaussian observations with changing mean values. Motivated by the heavy tail, Laplace-like data in the array based experiments, we derive a score-like statistic for testing whether the mean changes or not in Laplace data in Chapter 2. We then generalize this test statistic to a class of non-parametric test statistics and apply these robust statistics to detect change-points in array based data. In Chapter 3, we consider the abrupt mean change problem in the one parameter exponential family data. With the assumption that the number of change is unbounded, we derive a modified BIC to determine the number of change-points in the sequence and apply our method to detect DNA copy number changes in sequencing data. This modified BIC connects naturally to the second part of the thesis, where we consider model selection of smooth change-point models. In Chapter 4, we investigate the segmented line regression model and propose a slightly different smooth change-point problem. We derive a modified BIC for the smooth problem based on the Laplace's method. Because irregularities in the likelihood function vanish after smoothing, the derivation of this modified BIC is similar to the classic BIC. In the last chapter, we extend the modified BIC to other change-point problems.
Developing the anemone aiptasia as a tractable model for cnidarian-dinoflagellate symbiosis [electronic resource] : generating transcriptomic resources and profiling gene expression
Keywords: Genetics.

Coral reefs are animal-built structures that provide habitats for a disproportionately large number of marine species relative to the small percentage of the ocean that they cover. Corals, and some other cnidarians such as anemones, host dinoflagellates within the cells of their gastrodermal tissue. The dinoflagellates fix carbon photosynthetically and transfer it to the host; the dinoflagellates can provide up to 90% of the hosts' metabolic requirements. The symbiosis between the cnidarian host and its dinoflagellate symbiont is therefore the trophic foundation on which coral reef are built. Despite its importance, the molecular mechanisms controlling symbiosis establishment, maintenance, and breakdown remain poorly understood. Our lab is working to further develop the small sea anemone, Aiptasia, as a model system for studying cnidarian-dinoflagellate symbiosis. To this end, I sequenced the transcriptome of aposymbiotic Aiptasia, of symbiotic Aiptasia, and of the dinoflagellate symbionts. I then used these resources to perform gene-expression analysis comparing symbiotic and aposymbiotic anemones, which provided numerous testable biological hypotheses about both the structural basis of the symbiosis and the downstream metabolic effects of metabolite transfer to the host. These resources should serve as the foundation for future experiments in our laboratory and more widely in the field of coral biology.
Development of optically active cyclopentadienyl ruthenium complexes and their application in asymmetric catalysis [electronic resource]
Keywords: Chemistry.

Novel ruthenium complexes were developed containing a cyclopentadienyl (Cp) ligand tethered to a chiral sulfoxide, which also serves as a ligand. These complexes were synthesized via a [3+2] dehydrogenative cycloaddition between a Ru-[pi]-allyl complex and a terminal acetylene. Using the cycloaddition as a key step, the desired sulfoxide-ligated complexes could be prepared in six linear steps without the use of toxic metallating reagents such as thallium salts. A diverse library of complexes could be accessed through this method, which speaks to the robust nature of the key cycloaddition step. Using these complexes, a CpRu-catalyzed branched-selective asymmetric allylic alkylation (AAA) was developed. Using this method, various oxygen nucleophiles could be alkylated with allyl chloride electrophiles to provide branched ethers, esters and alcohols with high levels of regio- and enantioselectivity. These complexes also were effective in catalyzing an asymmetric redox bicycloisomerization to generate complex [3.1.0]- and [4.1.0]-azabicycles from simple propargyl alcohol substrates.
Developmental enhancers [electronic resource] : ancient origins, neofunctionalization, and pleiotropy
Keywords: Genetics.

In this work, I present two studies of the evolution and function of developmental enhancers. In the first study, I describe the discovery of the first examples of cis-regulatory elements that are conserved across the two great clades of the bilaterian tree (deuterostomes and protostomes). These bilaterian conserved regulatory elements (Bicores) are developmental enhancers that respond to key signaling pathways and have been conserved for approximately 650 million years. In vertebrates, Bicores have neofunctionalized to drive expression in the central nervous system. In the second study, I present a genome-wide set of putative enhancers that function in the development of the mammalian neocortex. These elements, identified through ChIP-seq, are validated through both computational and experimental approaches. I show that many elements are anciently conserved beyond mammals, and we show that older elements are more likely to be pleiotropic. Pleiotropic elements most likely function in other aspects of central nervous system development, and elements that are conserved to zebrafish function in the developing zebrafish forebrain. I also provide evidence that specific repeat families have played a major role in the generation of enhancers that function in neocortex development. Finally, in the conclusion, I discuss how enhancer neofunctionalization and pleiotropy fit into a model of enhancer evolution and the evo-devo framework.