VictorJuiz/thesis huggingface dataset:
Semantic-based information extraction of biomedical definitions [electronic resource]
Keywords: Electrical Engineering

It is well known that the volume of biomedical literature is growing exponentially and that scientists are being overwhelmed when they sift through the scope and diversity of this unstructured knowledge to find relevant information. Prior work on addressing this problem has focused on methods to search for relevant publications and to identify relevant parts of publications. There has been much less research on methods that assist in extracting knowledge from biomedical literature. To tackle this challenge, I present a novel method to support the acquisition of structured knowledge from unstructured text. I have applied my method to support the challenge of identifying rule-based definitions of disease phenotypes. Because background knowledge of complex and diverse medical conditions is critical to undertaking information extraction, I have developed a semantic-based approach. Specifically, I use existing background knowledge to incorporate domain-relevant semantics, such as semantic similarity and rules, into a method for finding publications and the parts of texts within that contain knowledge about phenotype definitions and for identifying the rule or rule format that correctly encodes a phenotype. I have evaluated my method in the autism phenotyping domain, and found that incorporating structured domain knowledge into information extraction provides better accuracy and higher relevance of results than alternative term-based approaches. My novel method can help scientists to rapidly identify and formalize the complex domain knowledge that is emerging in published research findings. My method is also widely applicable to other information extraction challenges where there is a need to accurately extract computer-interpretable definitions, constraints, and policies from text.
Separable problems in optimal cooperative control of networked systems [electronic resource]
Keywords: Aeronautics and Astronautics

This thesis characterizes a class of separable optimal cooperative control problems. We show that a simple factorization condition provides a unified technique that allows the problem to separate into several independent subproblems. The technique generalizes many of the previously known computational approaches and further enables us to solve a new class of previously unsolvable problems. The optimal solutions are computed explicitly in a distributed fashion via a series of Riccati equations whose size grows linearly with the problem size, therefore the optimal cooperative control can be easily computed via standard techniques for conventional optimal control problems. Furthermore, the separated problems provide a better understanding of the dynamics of the optimal controller. We illustrate two application examples including a salvo guidance problem and a network design problem for a team of networked missiles.
Shugendō in the Tokugawa period [electronic resource] : Mount Ōmine as imaginary space and place of practice
Keywords: Religious Studies

Shugendō is a Japanese tradition of mountain asceticism co-opted by the schools of Japanese Esoteric Buddhism. This study concentrates on one of the most historically important sites of the tradition, Mount Ōmine, and the stations along the annual, multiple-day 'mountain entry' ritual called the Northern Okugake. Working mainly with the tradition's primary texts, it demonstrates how the tradition reinvented the imaginary landscape, anchoring legends and cosmology onto the rocks, caves, and sources of water that composed the material landscape of the place. The dissertation demonstrates that Shugendō texts present us with a valuable view into Esoteric Buddhism that has been overlooked by scholars of Japanese Esoteric Buddhism in particular, and Japanese religions in general.
Sidewall silicon carbide emitters for microfabricated Barkhausen-Kurz Terahertz vacuum electronics [electronic resource]
Keywords: Electrical Engineering

The frequency band from 300 GHz to 3.0 THz is rich in potential applications, but there is a lack of efficient sources. This "THz gap" arises from the sharp decrease in the efficiency and power output of solid-state electronic amplifiers at frequencies above 100 GHz along with the unavailability of compact, uncooled optical sources for wavelengths longer than the infrared. Future THz systems hold great promise for leveraging the unique properties of THz waves, which are long enough in wavelength to be penetrating through clothing and skin, but are short enough to be useful for imaging, are resonant with complex molecular bonds, and are low enough in energy to be safe and non-ionizing. In addition to applications in security screening and medical imaging, continuous-wave THz systems would also enable short-range extreme wideband communications. This thesis proposes a micro-fabricated Barkhausen-Kurz ([mu]-BK) oscillator as a promising candidate THz source. The Barkhausen-Kurz concept is a general electronic oscillator principle developed nearly a century ago. The [mu]-BK oscillator has significant advantages over other vacuum electronic devices, promising high DC-to-THz efficiency and low startup current requirements. This device achieves a strong coupling between the resonant cavity structure and the electron beam current, even when operated at harmonics of the electron orbit frequency, by extracting energy over multiple passes of favorably phased electrons confined within a potential well. This enables high space charge, low beam impedance, and efficient energy extraction. The need for an emitter integrated into a parabolic potential well poses a major fabrication challenge. The basic fabrication process for the cavity and integrated poly-silicon carbide thermionic cathode has been demonstrated, providing the foundation for developing stable cathodes for injecting a sheet electron beam and for optimizing the electrode geometry for defining a parabolic potential well. Thermionic emission, in contrast to field emission, has the major advantage of the decoupling the control of electron current intensity (determined by temperature) from the operating frequency (determined by electrode bias). This thesis develops the motivation for the [mu]-BK oscillator as a promising candidate for efficient integrated THz circuits. The fabrication process and results for the sidewall lateral emitter integrated into a silicon [mu]-BK cavity process are detailed. Experimental results on emission current in integrated diode test structures in vacuum are reported, that enable the design of a new vacuum electronic technology that combines electron emitters, coupled resonant cavities, and lithographically shaped electrodes in a single substrate. This new class of efficient THz vacuum electronic integrated circuits promises to bridge the THz gap.
Sign and signal [electronic resource] : deriving linguistic generalizations from information utility
Keywords: Linguistics

Why do languages have such different phonological processes even though all speakers share the same cognitive, articulatory and perceptual constraints? American English preserves sounds such as /p/ and /g/ even though they are absent from the sound systems of many of the world's languages, but reduces sounds such as /t/ even though it is one of the most frequently used sounds cross-linguistically. In contrast, Romance languages reduce /s/, which American English preserves. What makes American English have this particular set of phonological processes and not processes that affect other languages? I show that by assuming that speakers attempt to maximize the amount of information they transmit while minimizing the amount of effort required to transmit that information, it is possible to determine which sounds are more likely to be affected by reduction processes and which sounds are more likely to be preserved in each language. Unlike cognitive, perceptual and articulatory constraints, which are the same for speakers of all languages, the amount of information languages assign to linguistic elements, such as individual sounds, varies markedly. The more information a sound carries, the more effort speakers are willing to expend to transmit it faithfully to listeners. The trade-off between maximizing information and minimizing effort forms the basis for a new framework I call MULE (Most information Utility, Least Effort). MULE predicts preservation and reduction patterns in English and Arabic at the levels of performance, competence and change, thereby providing a partial answer to the actuation problem (Weinreich et al. 1968). MULE also predicts cross-linguistic generalizations. I show that in American English, Egyptian Arabic and Spanish, highly informative sounds are more likely to benefit from the perceptual prominence of the onsets of stressed syllables. Similarly the balance between effort and information successfully predicts cross-linguistic asymmetries between the frequencies of less effortful sounds and more effortful sounds. As such, MULE enhances the explanatory power of linguistic theory, and provides a disciplined way to integrate phonetics and information theoretic considerations.
A signal processing approach to overcome data integrity challenges in flash SSD design [electronic resource]
Keywords: Electrical Engineering

Recently, flash-based Solid State Drives (SSD's) have emerged as a faster and more efficient alternative to hard drives. However, their higher cost is still an obstacle for their widespread use. Manufacturers have significantly reduced the cost by aggressively scaling the technology but this reduction has come at a price in lifetime, speed, and reliability. As the cell size shrinks and more bits are programmed into each one of them, interaction between neighboring cells increases significantly leading to noisier writing and unreliable reading of the flash memory. It is thus a signal processing challenge to write and read back reliably. This thesis proposes methods to overcome this challenge.
Silicon nanocrystals, dust to gold [electronic resource] : progress in material, devices and synthesis
Keywords: Electrical Engineering

Over the past half century silicon has become a dominant material for electronics but it has remained a very poor optical material. Bandwidth limitations in electronics are currently being seen as a problem. A similar situation to what happened on the long haul transport where we switched from the copper pair to optical fiber communication, may occur at the chip scale through integration of cheap on-chip optical devices. We consider two ways forward for silicon to remain a relevant material for lightwave communication in this era despite challenges posed by the indirect gap and free carrier absorption. In specific, we look at silicon nanocrystals (Si-NC) as a light emitting material to show progress in turning this indirect gap material into an efficient emitter. First we show through a highly sensitive optical absorption spectroscopy technique (photothermal deflection spectroscopy) that the negative effective mass electron states in Si-NC shift down in energy thereby reducing the energy gap at the direct transition. This effect is responsible for low amounts of visible range emission reported in small crystals; as opposed to the emission from band gap minima at the X valley attributed with majority of the near IR emission. Thus we confirm through a direct measurement the minima in density of states at the [gamma] valley from splitting of the negative and positive effective mass states. We compare the shift in a few of these states with a model for quantum confinement in the nanocrystals surrounded by oxide using a simple parabolic potential well model. We then show how resonant nanocavities should be optimized for low gain broad emitters like Si-NC. These cavities offer reduced mode volumes at the cost of quality factors such that "bad emitters" like Si-NC may couple with the cavity and ultimately offer a higher likelihood of observing Purcell enhancement. FDTD simulations show Q factors above 25000 and mode volumes below 0.6([lambda]/n)3 in silicon rich oxide, which has a refractive index of only 1.7. Finally we show a novel technique to make Si-NCs only on selected areas of the wafer: we direct-write tracks of silicon nanocrystals using a ps UV laser. It is possible to obtain 4 orders of magnitude throughput increase using this process as an alternative to oven annealing while also making localized nanocrystal precipitation a possibility. The tracks show emission enhancement over bare silicon rich oxide films and emission intensity comparable to that observed in conventionally-processed Si-NCs. We study variations in emission spectra, nanocluster phase and film stress across these tracks showing that ultimate limitation in throughput is film densification leading to compressive stress on the clusters that increases interfacial defects leading to emission quenching.
Single-cell deep profiling of immune signaling and drug responses in normal and malignant human hematopoiesis [electronic resource]
Keywords: Microbiology and Immunology

The human hematopoietic system is a complex mixture of morphologically and functionally distinct cell types. Using high-dimensional single-cell cytometry, functional behaviors in a wide number of cell types can be monitored simultaneously ("deep profiling"), enabling new insights into the structure and relationships of the overall system. Presented in this dissertation are several incremental technical and informatic steps that contributed to this holistic approach to single-cell biology. Using 30-parameter mass cytometry, deep profiling was used to recover the developmental continuum of healthy bone marrow and create a detailed map of the atypical functionally related cell types in a case of oligoclonal pediatric acute myeloid leukemia. These examples demonstrate the utility of a single-cell deep profiling paradigm in attaining an informative snapshot of healthy and malignant human hematopoiesis.
Single-molecule fluorescence and super-resolution imaging of Huntington's disease protein aggregates [electronic resource]
Keywords: Chemistry

Single-molecule, super-resolution fluorescence microscopy is a powerful technique for studying biological systems because it reveals details beyond the optical diffraction limit (on the 20-100 nm scale) such as structural and conformational heterogeneity. Further, single-molecule imaging measures distributions of behaviors directly through the interrogation of many individual molecules and reports on the nanoscale environment of molecules. Sub-diffraction imaging adds increased resolution to the advantages of fluorescence imaging over the techniques of atomic force microscopy and electron microscopy for studying biological structures, which include imaging of large fields of view in aqueous environments, specific identification of protein(s) of interest by fluorescent labeling, low perturbation of the system, and the ability to image living systems in near real-time (limited by the time required for super-resolution sequential imaging). This dissertation describes the application of single-molecule and super-resolution fluorescence imaging to studying the huntingtin (Htt) protein aggregates that are a hallmark of Huntington's disease and that have been implicated in the pathogenesis of the disease. The intricate nanostructures formed by fibrillar Htt aggregates in vitro and the sub-diffraction widths of individual fibers mark the amyloids as important targets for high-resolution optical imaging. The characterization of Htt aggregate species is critical for understanding the mechanism of Huntington's disease and identifying potential therapies. Following an introduction to single-molecule, super-resolution imaging and Huntington's disease in Chapter 1, Chapter 2 describes the single-molecule methods, experimental techniques, Htt protein sample preparations, and data analysis performed in this dissertation. Chapter 3 discusses the development of super-resolution imaging of Htt protein aggregates and the validation of the images by atomic force microscopy. Chapter 4 continues the study of Htt by one- and two-color super-resolution with imaging of Htt protein aggregates over time from the initial protein monomers to the large aggregate assemblies of amyloid fibers. In Chapter 5, I detail our progress to-date in studying the earliest stages of Htt aggregation using zero-mode waveguide technology. Chapter 6 concludes the dissertation with a discussion of the results from additional projects comprising the effect of chaperonin proteins on Htt aggregation, extension of super-resolution Htt imaging to three dimensions, and cellular imaging of Htt aggregates. The future directions for these exciting projects are summarized with the expectation that research efforts directed in these areas will contribute to our understanding of Htt aggregation and Huntington's disease.
Single-molecule studies on transcriptional elongation in prokaryotes and eukaryotes [electronic resource]
Keywords: Applied Physics

Transcription, the process of copying genetic information stored in DNA into RNA, is fundamental to life. It is carried out by an extraordinary nano-machine called RNA polymerase (RNAP). Transcriptional elongation, during which RNAP moves along the DNA, adding one nucleotide at a time to the RNA transcript, is highly dynamic and regulated. The motion of RNAP is discontinuous and interrupted by pauses that play an essential role in gene regulation. Fundamental questions regarding the mechanisms of elongation and its modulation by transcription factors, however, remain unclear. In this dissertation, I focus on using high-resolution, optical trapping techniques to study the mechanisms of transcriptional elongation by both prokaryotic and eukaryotic RNA polymerases at the single-molecule level. First, I describe the studies on how the motion of single E.coli RNAP molecules is modulated by two universally conserved, essential transcription factors (NusA and NusG). From individual transcriptional elongation records, the rates of entering pause states, the pause state lifetimes, and the pause-free elongation speeds can all be extracted. By studying the effects of NusA (and NusG) on these kinetic rates as a function of the applied load, we were able to develop a quantitative kinetic scheme for elongation and pausing. This model not only explains the functions of NusA/NusG, but also provides insight into the mechanism of transcriptional pausing, which had previously been controversial. Second, a novel optical-trapping assay capable of directly probing elongation by individual eukaryotic RNA polymerase II (RNAPII) molecules will be described. We find that the RNAPII trigger loop, an evolutionarily conserved protein subdomain, not only affects each of the three main phases of elongation, namely: substrate binding, translocation, and catalysis; but also plays a critical role in controlling the fidelity of transcription. Our data also support a Brownian ratchet model for elongation which incorporates a secondary nucleotide binding site.
Size-expanded ribonucleic acids (xRNAs) [electronic resource] : a novel component in siRNAs for investigating the steric restrictions of RISC in RNAi
Keywords: Chemistry

This thesis project describes the synthesis and use of size-expanded ribonucleic acids (xRNAs) as unnatural components in small interfering RNAs (siRNAs), which serve as a novel set of steric probes for investigating and identifying size restrictions that exist in the active site of the RNA-induced silencing complex (RISC), a critical protein complex in the RNA interference (RNAi) mechanism. xRNAs are analogous to natural RNAs, in which they retain canonical Watson Crick base-pairing groups, except their nucleobases are expanded linearly by 2.4 Å via benzo-fusion. In this report, the synthesis of the entire set of four xRNA nucleosides and their photophysical properties are described. Two of the xRNA nucleosides (i.e. rxA and rxU) are then converted to their corresponding phosphoramidites for use in automated RNA synthesis to synthesize various sets of xRNA-substituted siRNA strands for biophysical and biological studies. RNAi activity studies in HeLa cells using a firefly/Renilla luciferase dual reporter assay showed that xRNA substitutions in the antisense strand displayed poor RNAi activity in the middle of the sequence (positions 7-14) but were generally well tolerated near the 5'- and 3'-ends. Most significantly, single xRNA substitutions at the 3'-end showed RNAi activity that was more potent than that of unmodified siRNAs. Thermal denaturation studies revealed small changes in melting temperature (+1.4 to --5.0 °C); xRNA substitutions in the middle were found to be more thermodynamically destabilizing whereas the ends were shown to be stabilizing. Serum stability studies showed that xRNA-containing siRNAs have longer half-lives in human serum than unmodified siRNAs. Finally, xRNA-substituted siRNA strands and duplexes showed interesting position-dependent fluorescent properties, while CD spectroscopy experiments revealed that xRNA-substituted siRNAs does not greatly distort the native A-form helical structure of the duplexes. Taken together, the data demonstrate the utility of xRNA nucleobases as size-expanded mechanistic probes for RNAi research.
Small changes big impact, ligand influence on dioxygen, semiquinone, and phenoxyl radical copper complexes [electronic resource]
Keywords: Chemistry

Reductive activation of dioxygen by copper to generate potent oxidants for multi- electron organic transformations is exploited extensively in biological systems. This thesis focuses on two types of multi-electron oxidants: Cu2O2 complexes and copper complexes with redox-active ligands. The goal of this work is to identify the influence of nitrogen containing ancillary ligands on properties of dioxygen, semiquinone and phenoxyl radical complexes of copper. This work is aimed primarily at synthetic chemists interested in rational design of ligands for creating bio-inspired oxidants and oxidation catalysts. Chapter 1 of this thesis reports the identification of a Density Functional Theory (DFT) protocol for deriving structure-property relationships in Cu2O2 complexes. Chapter 2 of this thesis applies towards modeling electronic spectra, the DFT protocols that were validated in Chapter 1 for modeling thermodynamics. Chapter 3 of this thesis describes the properties and reactivity of Cu2O2 complex generated from a new hybrid permethylated-amine-guanidine ligand based on a 1,3- propanediamine backbone (2L). Chapter 4 of this thesis describes the characterization of an intermediate (C) that is observed in both phenol hydroxylation and catechol oxidation with the SP core supported by N1, N2-di-t-butylethane-1,2-diamine (DBED). Chapter 5 of this thesis describes the influence of sulfanyl substituents on the optical and redox properties of copper-bonded phenoxyls.
Small-sample behavior of importance sampling estimators [electronic resource]
Keywords: Electrical Engineering

This thesis studies the small sample behavior of importance sampling estimators under an importance measure that is not necessarily optimal. We first study the asymptotic behavior of IS estimators for sums of random variables when the sample size increases exponentially. We next propose logarithmic relative accuracy as a new measure for estimator accruacy. Finally, we extend the result to the importance sampling estiamtors for slow Markov random walks.