VictorJuiz/thesis huggingface dataset:
Transcription factor-mediated lineage conversion into neuronal cells [electronic resource]
Keywords: Microbiology and Immunology.

Induced pluripotent stem cells technology has introduced many possibilities for regenerative medicine as therapy can potentially be tailored to specific patients. More recently, direct reprogramming using transcription factors to convert somatic cells into neuronal cell types has further bent the paradigm that the adult cell fate is fixed. Previous studies have identified specific transcription factors that can directly generate neurons from fibroblasts. Here, we hypothesized that a different combination of transcription factors can generate specific neuronal subtypes. In particular we looked at midbrain dopamine neurons that are implicated in Parkinson's disease. We identified 5 transcription factors Ascl1, Nurr1 Lmx1a, En1, FoxA2 that can convert mouse fibroblasts into midbrain dopamine neurons. In murine and human embryonic stem cells, we identified 6 transcription factors Ascl1, Nurr1, Lmx1a, En1, FoxA2 and Pitx3, together with an exogenous supply of WNT1 protein that can generate dopamine neurons of the central nervous system fate. These dopamine neurons express midbrain-type markers, produce dopamine and exhibit electrophysiological properties akin to midbrain dopamine neurons. This study also suggests that a different combination of neuronal transcription factors might generate neurons of other subtypes, such as inhibitory or adrenergic neurons. Generation of subtype neurons could have important implications for drug studies, disease modeling and potential clinical applications.
Translational Allele-Specific Expression (TASE) in Humans
Keywords:  Department of Biology
Biology
Molecular Genetics
RNA Sequencing
Ribosome Profiling
Allele-Specific Expression
Thesis

Protein expression levels can determine disease genesis and progression. However, various processes occur between DNA and protein that can affect protein expression levels in the cell. Transcriptional allele-specific expression (ASE) is a process between DNA and RNA that yields differential expression of maternal and paternal alleles in the RNA. The mechanism behind this phenomenon has been a widely understood and applied to various cancer research initiatives. However, little work has been done to understand a similar process that happens between RNA and protein, translational allele-specific expression (TASE), where differential translational preference of alleles from mRNA contributes to differential expression of those alleles in proteins. Detecting TASE is more difficult because the same protein sequence could have come from various mRNAs and degradation makes it hard to quantify and sequence proteins accurately. Although few research papers have revealed the potential of TASE in yeast, none have shown this in humans. Here, we use a previously developed method to model and detect TASE in human samples. We develop a sensitive pipeline to quantify allelic expression in free mRNA and compare it to the quantity of those same alleles in mRNA that is actively being translated by ribosomes (‘ribosome-protected’ mRNA) of thirty human samples. We then use a bootstrapping method to detect the significant in the difference of allelic expression in these two groups of mRNA. We find that translational allele-specific expression occurs in almost all of the human samples, some alleles of which might be important for disease genesis.
Transmission and interpretive facilitation [electronic resource] : teaching Hebrew bible in Jewish elementary schools
Keywords: Education.

This dissertation explores how elementary school Jewish studies teachers understand the goals of Jewish education and the pedagogies they adopt to achieve these goals. Jewish education theorists and Jewish institutions make two demands on their teachers: to transmit Jewish knowledge and to cultivate students' interpretive autonomy. Do teachers in real Jewish studies classrooms understand their teaching in these terms? This study observed whole class text discussions in six Jewish studies classrooms in Jewish day schools and conducted stimulated-recall interviews (SRIs) with the teachers after every observation. Analysis of classroom observations found that the pedagogy of transmission was most prevalent, but there were also teachers who adopted the pedagogy of interpretive facilitation. Analysis of the SRIs revealed that teachers in this study articulated deeply held educational goals that motivated their pedagogical choices. But, teachers did not primarily articulate their goals in the language of the dual demands, transmission and interpretive autonomy. Instead, teachers described their goals either as religious or literary. Only three teachers mentioned the dual demands. Of these three teachers, two saw the goals of transmission and interpretive autonomy as mutually exclusive and one saw them as complementary. This study concludes with a comparative analysis of these three teachers and argues that much more theoretical attention needs to be paid to explaining why cultivating students' interpretive autonomy is fundamentally a religious responsibility.
Traversing the roads to Osorezan [electronic resource] : priests, pilgrims, and spirit mediums at a pilgrimage site in contemporary Japan
Keywords: Religious Studies.

The Sōtō Zen temple Osorezan Bodaiji in the northernmost part of Aomori prefecture is renowned as a place where the spirits of the dead cross into the other world and blind spirit mediums called itako perform séances. However, from the early modern period Osorezan has undergone multiple shifts in identity. The temple began its history as a local site of hot spring cures and recreation, was gradually identified with Jizō and this-worldly blessings, and then offered opportunities for pilgrims to participate in memorial services. The itako began coming to Osorezan in the contemporary period, and today only two remain and perform séances at the temple festivals. This dissertation positions the pilgrimage site Osorezan Bodaiji "in situ" within the economic, historical, and religious networks of Shimokita peninsula and investigates the roles these factors have played in its development into a major pilgrimage site. I argue that the main story of Osorezan is not the itako, or even the dead, but a wide variety of human actors that shaped the landscape and practice at the mountain. Although Osorezan is a major tourist destinations and operates on the margins of organized Buddhism, it nevertheless shares many similarities with traditional pilgrimage sites. The managing priests from Entsūji pursued political alliances, published and propagated an engi, origin tale, performed sect-sanctioned prayer services, and responded to social tragedy such as earthquakes with temple installations. Even today, pilgrims from the local area come to practice seasonal worship, make offerings to Bodhisattvas and Buddhas on the site, and participate in standard rituals for the ancestors. Osorezan faces challenges such as decline in local confraternity practice that may threaten the future of the mountain as a place of belief.
Tropical coordinates on the space of persistence barcodes [electronic resource]
Keywords: Mathematics.

In the last two decades applied topologists have developed numerous methods for `measuring' and building combinatorial representations of the shape of the data. The most famous example of the former is persistent homology. This adaptation of classical homology assigns a barcode, i.e. a collection of intervals with endpoints on the real line, to a finite metric space. Unfortunately, barcodes are not well-adapted for use by practitioners in machine learning tasks. In this dissertation, I identify classes of max-plus polynomials and tropical rational functions that can be used as coordinates on the space of barcodes. All of these are stable with respect to standard distance functions (bottleneck distance, Wasserstein distances) used on the barcode space. I demonstrate how these coordinates can be used by combining persistent homology with SVM to classify numbers from the MNIST dataset. In order to identify functions on the barcode space, I find generators for the semirings of tropical polynomials, max-plus polynomials and tropical rational functions invariant under the action of the symmetric group. The fundamental theorem of ordinary symmetric polynomials has an equivalent in the tropical and max-plus semirings. There are interesting differences if we consider the tropical polynomial semiring with nr variables that come in n blocks of r variables each and are permuted by the symmetric group. As opposed to the ordinary polynomial case, the semiring of r-symmetric tropical polynomials is not finitely generated, but the semiring of r-symmetric tropical rational functions is.
Tropical instability waves and mixing in the equatorial Pacific Ocean [electronic resource]
Keywords: Environmental Earth System Science.

The unique dynamics of the equatorial oceans play an important role in the El Nino - Southern Oscillation (ENSO) and the ocean's meridional overturning circulation (MOC), both of which are critical processes that drive global climate variability on a range of time-scales. This dissertation makes a number of contributions to our understanding of equatorial ocean dynamics, lateral and vertical mixing at the equator, the behavior of equatorial waves and deep equatorial mixing, with implications for both ENSO and the MOC. The main contributions are: 1) Tropical instability waves (TIWs), the main drivers of lateral eddy mixing in the eastern equatorial Pacific, share a number of dynamical features with submesoscale flows in the mid-latitudes. In particular, their formation depends on the detailed frontal dynamics and sharp vertical gradients around their fringes, with implications for TIW energetics and the accurate representation of TIWs in low-resolution ocean models. 2) TIWs drive modulations in vertical mixing by altering the vertical shear of the Equatorial Undercurrent (EUC) through horizontal vortex stretching. This modulation can drive net sea surface cooling over the eastern Pacific cold tongue that may partially offset the warming driven by TIW lateral mixing. The magnitude of the net cooling depends on the mixing scheme used to parameterize vertical mixing, with implications for the role of TIWs in the mixed-layer heat budget in different ocean models. 3) Downwelling (upwelling) equatorial Kelvin waves can drive large decreases (increases) in the amplitude of the TIW field in the eastern equatorial Pacific and thus TIW-driven lateral and vertical mixing. The Kelvin waves alter the strength and structure of the background flow from which the TIWs gain energy, resulting in complex changes to the TIW energy budget. One major sink of TIW energy, the downward radiation of waves, is strongly altered with implications for deep and abyssal equatorial ocean circulation. 4) Mixing in the abyssal equatorial Pacific can exhibit a seafloor-intensified vertical structure even over smooth topography. The generation and breaking of lee waves over smooth topography at low latitudes is one possible mechanism that could contribute to this mixing. However, downward-propagating equatorial waves generated at the surface by TIWs or wind events could also supply energy for seafloor-intensified mixing through two possible mechanisms, wave trapping due to the horizontal component of Earth's rotation and inertial instability initiated by wave-driven displacement of fluid away from the equator. These results suggest that more attention should be devoted to measuring and understanding mixing over smooth topography in the abyssal equatorial oceans because of its potential role in the global overturning circulation.
Two models on limit order trading [electronic resource]
Keywords: Mathematics.

In this thesis we study two limit order trading models based on the one of Avellaneda and Stoikov (2008). For the first one, we study Avellaneda-Stoikov model under the condition when the underlying price is mean reverting. Our main result is that when time is far from the terminal, the optimal price for bid and ask limit orders is constant, which means that it does not track the underlying price. Numerical simulations confirm this behavior. When the underlying price is mean reverting, then for times sufficiently far from terminal, it is more advantageous to focus on the mean price and ignore fluctuations around it. Mean reversion suggests that limit orders will be executed with some regularity, and this is why they are optimal. We also explore intermediate time regimes where limit order prices are influenced by the inventory of outstanding orders. The duration of this intermediate regime depends on the liquidity of the market as measured by specific parameters in the model. The second model we study is a price impact model where the underlying price is affected by the mean field terms representing existing limit orders in the market. The main result on this model is that there are two different regimes for the representative trader in the solution of MFG: In the beginning, he trades aggressively which results in a large price impact; after a short period of time, he trades, by expectation, approximately symmetric about the underlying price. As a function of time, the price impact decays exponentially in the solution of MFG. Moreover the expectations of optimal prices for the representative trader are constants symmetric about a level close to the terminal value of expected underlying price.
Two-dimensional spatial imaging of charge transport in germanium crystals at cryogenic temperatures [electronic resource]
Keywords: Physics.

In this dissertation, I describe a novel apparatus for studying the transport of charge in semiconductors at cryogenic temperatures. The motivation to conduct this experiment originated from an asymmetry observed between the behavior of electrons and holes in the germanium detector crystals used by the Cryogenic Dark Matter Search (CDMS). This asymmetry is a consequence of the anisotropic propagation of electrons in germanium at cryogenic temperatures. To better model our detectors, we incorporated this effect into our Monte Carlo simulations of charge transport. The purpose of the experiment described in this dissertation is to test those models in detail. Our measurements have allowed us to discover a shortcoming in our most recent Monte Carlo simulations of electrons in germanium. This discovery would not have been possible without the measurement of the full, two-dimensional charge distribution, which our experimental apparatus has allowed for the first time at cryogenic temperatures.
Two-way coupled compressible euler-lagrangian simulation to investigate cavitation and bubbly shock propagation [electronic resource]
Keywords: Mechanical Engineering.

Cavitation is one of the most significant performance limiting phenomena encountered in liquid handling machinery and marine propulsion systems. Control of cavitation plays a critical role in the design of such systems. Ineffective control of cavitation can result in a significant erosive damage to marine propellers, decreased efficiency, unexpected noise/vibration and limited thrust of propulsion systems. This study aims at physics-based modeling of inter-phase phenomena encountered in cavitating flows to develop a compressible Eulerian-Lagrangian (E-L) framework for cavitating and non-cavitating bubbly flows. A fine-resolution DNS was performed to investigate wall reflection of bubbly pressure wave and to model bubble-bubble interaction from Rayleigh-Plesset equation. The amplification of pressure at wall is a function of bubble size, magnitude of incident pressure wave and surface tension. It does not depend on void fraction, which implies that even the presence of small bubbles near a wall in two-phase flows with low void fraction can cause damage to wall surface. A two-way coupled compressible E-L framework has been developed. Such methodology for predicting micro-dynamics of bubbles in bubbly shock problem worked very well to match FT-DNS result, which is a fine resolution DNS that tracks/resolves interface between two phases. Even with small number of bubbles in a 2-D geometry fundamental cavitation phenomena such as formation/detachment of sheet cavity due to re-entrant jet and development into cloud cavity could be observed. Bubble-bubble interaction is crucial for compressible E-L framework in terms of stability and accuracy, particularly for cavitating flows with high number density of bubbles. A bubble-bubble interaction model is specially designed for kernel interpolation based E-L solvers and Kubota's BBI model.
Ultrafast electrically driven processes in phase change materials [electronic resource]
Keywords: Applied Physics.

Phase change materials are being actively developed for nonvolatile memory applications due to their ability to switch between crystalline and amorphous phases, with highly contrasting electrical and optical properties, controllable by application of electrical pulses. In particular, the crystallization occurs through a thermal mechanism when the amorphous phase is heated beyond the crystallization temperature. In order to achieve these temperatures using voltages found in ordinary electronic devices, it is important that the highly resistive amorphous phase undergoes a so-called "threshold switching" process, whereby a sufficiently strong applied field induces a drastic increase in material conductivity. This process has been studied for decades but is still not well understood, with recent experiments suggesting a possible lower limit for the onset time of threshold switching, of order a few nanoseconds. Here, single cycle picosecond-duration terahertz pulses, generated from a pulsed laser source, are used as an ultrashort electric field bias, in order to investigate the picosecond time-scale response of amorphous phase change materials Ge2Sb2Te5 and Ag4In3Sb67Te26. Our results indicate that threshold switching is able to occur within this sub-picosecond pulse duration. Upon application of a series of pulses above a threshold of a few hundred kV/cm, we observe terahertz-driven filamentary crystallization, as evidenced by optical microscopy, microwave impedance microscopy, and x-ray diffraction studies. These results suggest that threshold switching occurs through a field-driven electronic tunneling process. Therefore, threshold switching is not a time-limiting factor for the thermal crystallization process, and amorphous phase-change materials could be considered for applications as ultra-fast resistance switches.
Ultrafast terahertz-driven ionic response in thin film ferroelectric oxides [electronic resource]
Keywords: Electrical Engineering.

Ferroelectric materials comprise non-centrosymmetric unit cells with permanent electric dipole moments switchable by electric fields, exhibiting strong coupling between polarization, strain, and electronic degrees of freedom. The dynamics of the ferroelectric polarization underlies their functionality but these processes, and the speed limits determining how fast the polarization can change, remain largely unknown. In particular, the ability to all-optically generate significant modulations or reorientations in the ferroelectric polarization represents a key step towards terahertz-frequency information storage technologies, actuators, and optical modulators. From a more general perspective, the use of light to modulate the functional properties of ferroelectrics holds promise for both directing these degrees of freedom and for elucidating their fundamental properties. Previous theoretical predictions indicate that large-amplitude polarization modulations can be achieved on hundreds of femtosecond time-scales, and studies with hundreds of picosecond to nanosecond time-resolution using electrical bias pulses have provided evidence for large amplitude modulations or switching of the polarization. Here we use terahertz pulses as an all-optical bias to apply sub-picosecond duration electric fields to BiFeO3 and BaTiO3 thin films. We show that these generate large amplitude changes in the ferroelectric polarization. In BiFeO3 we used the second harmonic light generated by the thin film as a structural probe and observed modulations in the intensity of second harmonic light corresponding to on-off ratios of 220x, gateable on few hundred femtosecond time-scales. These effects are enhanced through the use of rare-earth-doping to position the sample at a morphotropic phase boundary where the electromechanical and nonlinear-optical responses are enhanced but where the dynamical response of these materials has not previously been explored. In BaTiO3, we probed the atomic-scale response by femtosecond x-ray scattering techniques. We show that electric fields applied perpendicular to the ferroelectric polarization drive large amplitude displacements of the titanium atoms along the ferroelectric polarization axis, comparable to that of the built-in displacements associated with the intrinsic polarization. These transient polarization modulations are followed by long-lived vibrational heating effects driven by resonant excitation of the ferroelectric soft mode, as reflected in changes in the c-axis tetragonality. These measurements define the fastest speeds on which nanoscale ferroelectric devices can be manipulated by electric fields and open up novel opportunities for dynamic optomechanical strain engineering without activation of electronic degrees of freedom.
Understanding degradation mechanisms and improving long-term performance of organic solar cells [electronic resource]
Keywords: Materials Science and Engineering.

Organic photovoltaics (OPVs) attract interest because they can be printed rapidly and at low cost. Over the past decade, research directed towards increasing the initial power conversion efficiency has pushed the record device efficiency above 10%. However, in order to be a competitive technology, the performance must remain relatively stable over time. In this talk, I discuss mechanisms of degradation in materials and solar cells as well as suggest materials properties that will improve stability. First I discuss the bleaching of the absorber materials in air. I will show that dense, ordered film morphologies can stabilize materials -- in one case, by a factor of 2000. Next, I show that temperature induced degradation can occur in well-encapsulated solar cells when the materials have glass transition temperatures at or below operating conditions. Similarly, I discuss the effect of mobile molecules present in the films and show that purification aimed at reducing their content can improve thermal stability. In a solar cell made from a polymer with a high glass transition temperature, lifetimes can exceed 20 years. Finally, I discuss the light-induced degradation that occurs in the first several hundred hours of solar cell operation, even in the absence of oxygen. This degradation can reduce the short circuit current via a fullerene dimerization reaction, or it can reduce the open circuit voltage via the introduction of energetic disorder on the semiconducting polymer. I show that both degradation modes are reduced in films with a more ordered morphology. These findings provide guidelines for reducing thermal and photo-induced degradation and improving the long-term stability of OPVs.