VictorJuiz/thesis huggingface dataset:
Radio occultation of Saturn's rings with the Cassini spacecraft [electronic resource] : ring microstructure inferred from near-forward radio wave scattering

The Cassini spacecraft is a robotic probe sent from Earth to orbit and explore the planet Saturn, its moons, and its expansive ring system. Between May 3 and August 2 of 2005, we undertook a series of radio occultation experiments, during which the Cassini spacecraft operated in conjunction with the NASA Deep Space Network (DSN) to probe the rings at three distinct radio wavelengths. During our occultation experiments, Cassini flies behind the rings of Saturn as viewed from Earth and transmits coherent radio signals at wavelengths of 13 cm, 3.6 cm, and 0.94 cm, in the radio bands known as S, X, and Ka, respectively. These signals pass through the rings and are received and recorded on Earth at the large antenna complexes of the DSN. At each of the three transmitted frequency channels, the received signal comprises two components, i) a direct (coherent) component, which is the transmitted sinusoid, attenuated and phase shifted by the average effect of its interaction with the interceding ring material, and ii) a scattered (incoherent) signal component, comprising energy that is forward-scattered towards the receiver from all of the ring particles illuminated by the transmitting antenna's beam. The time- and spatially-averaged diffraction signature of ring microstructure---which forms when individual ring particles organize into large clusters or groups under the influence of collisional and self-gravitational forces---is superimposed on the scattered signal. Coherent radio waves transmitted by the Cassini spacecraft are diffracted at various locations in Ring A and B and indicate the presence of fine-scale structure showing periodic variation in optical depth, which we refer to as periodic microstructure (PM). We interpret the observed spectral signature using simple diffraction grating models, yielding estimates of the structural period that range between 100 and 250 meters. In all regions, the structure appears to be approximately symmetric in azimuth. Prior to Cassini, axisymmetric periodic microstructure was predicted by fluid dynamical theory and by the results of dynamical simulations of the rings, but was not observed experimentally. Our observations are among the first to directly observe PM in the rings, and to report estimates of its structural period and orientation in five distinct regions across Rings A and B.

Keywords: Electrical Engineering
Advisor: Marouf Essam primary advisor. Thesis advisor
Zebker Howard A. primary advisor. Thesis advisor
Enge Per advisor. Thesis advisor
Random Acts of Representative Democracy in the Orissa Panchayati Raj: A Test for Development Project and Electoral Empowerment Effects of Political Office Reservations for Women and Underrepresented Minorities

This papers leverages the randomization, popularized by “Women as Policy Makers: Evidence From A Randomized Policy Experiment in India” (Chattopadhyay and Duflo 2004a,) of reservations for women and underrepresented minorities in India’s Panchayati Raj system of hierarchical government bodies to identify their effects in Orissa, one of the country’s poorest states. It identifies interelectoral effects of reservations on group officeholding, project output and expenditure, and project type composition using a dataset of 710,189 government-sponsored development projects of 29 types that span 50,972 villages and the past nine financial years as well as two elections’ officeholder genders, reservations, and reelection statuses. The effect of reservations for women on their representation in unreserved seats is minimal, and underrepresented minority reelection rates are abysmal absent reservations. Effects on project expenditure and count are small though perhaps inconsistently present. Effects on project type composition mostly lack statistical and economic significance, (reservations for women,) or otherwise are of borderline economic significance but inconsistent across elections and administrative levels, (reservations for minorities.) Thus the case of Orissa may provide countervailing evidence to recent findings in the literature of reservations increasing disenfranchised groups’ electoral prospects as well as government project quantity, expenditure, or representativeness.

Keywords:  Department of Economics
Stanford Department of Economics
Panchayati Raj
reservations
election
India
Orissa
Thesis
Advisor: Mahajan Aprajit
Rational and combinatorial engineering of the met and axl receptor systems [electronic resource]

Ligand-receptor interactions govern nearly all cellular processes, and dysregulation leads to a range of diseases including cancer, autoimmune diseases, and regenerative disorders. As such, new strategies to target ligand-receptor interactions for therapeutic applications are an important area of research. To develop enhanced agonists and antagonists of the Met receptor, a critical target in cancer therapy and regenerative medicine, we engineered a fragment of the natural activating ligand (termed NK1). First, NK1 was evolved for improved stability using directed evolution. Then, using the activation mechanism of Met by NK1, the resulting enhanced stability mutants were rationally engineered for either agonistic or antagonistic activity. Next, the rationally engineered mutants were used as 'molecular tools' to provide further insights into NK1 structure and function. Finally, these insights supported additional rational engineering to generate further enhanced agonistic proteins. The antagonistic and agonistic proteins developed in this thesis hold promise as cancer therapeutics and diagnostics or for regenerative medicine applications, respectively. This work also supports native ligands as a promising starting point for development of therapeutic proteins.

Keywords: Bioengineering.
Advisor: Cochran Jennifer R. primary advisor. Thesis advisor
Giaccia Amato J. advisor. Thesis advisor
Khosla Chaitan
Swartz James R. advisor. Thesis advisor
Realism between metaphysics and science [electronic resource]

The aim of my dissertation is to understand what realism debates in philosophy of science should be about. To achieve this goal, a number of questions need to be addressed: What is the target of realism and antirealism in the philosophy of science, and what does it mean to be a realist or an antirealist? Does only realism in this debate imply a commitment to metaphysics, or are both realism and antirealism equally metaphysical positions? Is there really anything to be debated, or should we just be quietists about realism debates in philosophy of science? My answer is that, in its current form, the realism debate in philosophy of science is a skeptical debate, that is, antirealism is offered exclusively as an epistemic challenge to realism. This leads to an unsatisfactory stalemate between realism and antirealism, which often prompts a kind of quietism about these debates. While I reject this quietism as insufficiently supported by argument, I concede that the debate in its current shape is not satisfactory either. Instead I propose to change the target of realism debates away from claims about unobservables towards modal claims made in the sciences. Debates about the latter, I argue, can go beyond skeptical challenges to include semantic and metaphysical questions as well. Switching the target in this way makes the debate about realism in the philosophy of science more like realism debates in other fields.

Keywords: Philosophy
Advisor: Burgess Alexis
Ryckman Thomas primary advisor. Thesis advisor
Hussain Nadeem J. Z. advisor. Thesis advisor
Longino Helen E. advisor. Thesis advisor
Realized GARCH [electronic resource] : a joint modeling framework of return and realized measures of volatility

GARCH models have been successful in modeling financial returns. Still, much is to be gained by incorporating a realized measure of volatility in these models. In this thesis, we introduce a new framework for the joint modeling of returns and realized measures of volatility. A key feature of the Realized GARCH framework is a measurement equation that relates the observed realized measure to latent volatility. The new framework fills the gap between two lines of research on volatility modeling: GARCH and high frequency data. There are three major advantages of the Realized GARCH framework. First, the new framework nests most GARCH models as special cases and is, in many ways, a natural extension of standard GARCH models. The models with linear and log-linear specifications retain the simplicity and tractability of the classical GARCH framework; they imply an ARMA structure for the conditional variance and for the realized measures of volatility; and models in this class are parsimonious and simple to estimate. The measurement equation facilitates a simple modeling of the dependence between returns and future volatility that is commonly referred to as the leverage effect. Second, by incorporating the realized measures into the model, which are based on high frequency data and are much more accurate measurements for integrated volatility than daily squared returns, the Realized GARCH models provide a better performance in modeling and forecasting volatility. An empirical application with DJIA stocks and an exchange traded index fund shows that a simple Realized GARCH structure leads to substantial improvements in the empirical fit over to the standard GARCH model. This is true in-sample as well as out-of-sample. Moreover, the point estimates are remarkably similar across the different time series. Third, the measurement equation enables us to obtain additional insights on the bias and variance of different realized measures. Realized EGARCH model further extends the Realized GARCH model by reparameterizing the model and allowing different impacts of the leverage effect and residual measurement error on the conditional variance. The empirical results are in general consistent with the theoretical results in high frequency data literature and give practical guidance about how to use realized measures directly. The Realized EGARCH model is also applied to the exchange traded fund S& P500 index to study the volatility shocks during the financial crisis. We use this model to zoom into the events during the 2007-2009 period, and the model produces a daily series of volatility shocks. We link the announcements of events to large positive and negative volatility shocks.

Keywords: Economics
Advisor: Hansen Peter primary advisor. Thesis advisor
Hong Han advisor. Thesis advisor
Wolak Frank A. advisor. Thesis advisor
A regularized active-set method for sparse convex quadratic programming [electronic resource]

An active-set algorithm is developed for solving convex quadratic programs (QPs). The algorithm employs primal regularization within a bound-constrained augmented Lagrangian method. This leads to a sequence of QP subproblems that are feasible and strictly convex, and whose KKT systems are guaranteed to be nonsingular for any active set. A simplified, single-phase algorithm becomes possible for each QP subproblem. There is no need to control the inertia of the KKT system defining each search direction, and a simple step-length procedure may be used without risk of cycling in the presence of degeneracy. Since all KKT systems are nonsingular, they can be factored with a variety of sparse direct linear solvers. Block-LU updates of the KKT factors allow for active-set changes. The principal benefit of primal and dual regularization is that warm starts are possible from any given active set. This is vital inside sequential quadratic programming (SQP) methods for nonlinear optimization, such as the SNOPT solver. The method provides a reliable approach to solving sparse generalized least-squares problems. Ordinary least-squares problems with Tikhonov regularization and bounds can be solved as a single QP subproblem. The algorithm is implemented as the QPBLUR solver (Matlab and Fortran 95 versions) and the Fortran version has been integrated into SNOPT. The performance of QPBLUR is evaluated on a test set of large convex QPs, and on the sequences of QPs arising from SNOPT's SQP method.

Advisor: Saunders Michael A. primary advisor. Thesis advisor
Gill Philip E. advisor. Thesis advisor
Murray Walter advisor. Thesis advisor
Regulation of biofilm formation in two gamma-proteobacteria [electronic resource] : shewanella oneidensis MR-1 and vibrio cholerae A1552

S. oneidensis MR-1 is a dissimilatory metal-reducing bacterium. Under anaerobic conditions S. oneidensis MR-1 attaches to insoluble minerals such as Fe(III) and Mn(IV) oxides and can use these as alternative electron acceptors. Biofilms of S. oneidensis MR- 1 were previously found to be dependent on the mxd gene cluster (mxdABCD). This study identified environmental and genetic factors regulating mxd -dependent and -independent biofilm formation in S. oneidensis MR-1 and a putative function for mxdB in LPS biosynthesis. Physiological experiments determined electron donor starvation as a factor responsible for mxd induction. Tn5 mutagenesis identified two-component signaling system (TCS) ArcS/ArcA and a putative TCS BarA/UvrY as regulators of mxd expression. ccmC, important for cytochrome c maturation, was found to be involved in biofilm formation in S. oneidensis MR-1. Microarray analysis identified ccmC to play a role in aspects of anaerobic and fermentative metabolism in S. oneidensis MR-1. In conclusion, these data indicate a potential connection between energy metabolism of the cell, mxd and biofilm formation in S. oneidenis MR-1. The natural life cycle of the phylogenetically closest relative V. cholerae A1552 involves the transitioning of cells between different environmental surfaces such as the chitinous shell of Crustaceae and the epithelial layer of the human intestine and vice versa. Biofilms of V. cholerae A1552 vpsA and luxO mutants grown under hydrodynamic flow conditions were found to form pronounced, three-dimensional biofilms that resemble all aspects of wild type biofilms. By genetic experiments, it was shown that in hydrodynamically-grown biofilms this independence of vpsA is due to the expression of rpoS, which is a negative regulator of vpsA expression. Biofilms also underwent substantial metabolically controlled dissolution after 96 h that could be induced by a simple stop of medium flow across the biofilm. These studies indicate that metabolic conditions control the reversible attachment of cells to the biofilm matrix and are key in regulating biofilm cell physiology via rpoS. Furthermore, these results redefine the roles of vps and quorum-sensing in V. cholerae A1552 biofilms.

Advisor: Spormann Alfred M. primary advisor. Thesis advisor
Grossman Arthur (Arthur R.) advisor. Thesis advisor
Mudgett Mary Beth
Regulation of mast cell function by the membrane trafficking proteins RabGEF1 and Rabaptin-5 [electronic resource]

Cell surface receptor regulation maintains proper responses to external signals and disregulation of receptors can have drastic effects. We found that RabGEF1, a guanine exchange factor (GEF) for the endocytic regulating small GTPase Rab5, regulates IgE+antigen (Ag)-induced Ras signaling in mast cells and skin homeostasis in vivo. To further understand RabGEF1's role in mast cell function we investigated if RabGEF1 generally regulates mast cell signaling by examining a number of modes of mast cell activation. Like IgE+Ag stimulation, RabGEF1 deficient (-/-) mast cells demonstrated enhanced activation after exposure to stem cell factor (SCF), the ligand for the receptor tyrosine kinase c-kit. Enhanced responses correlated with delayed c-kit and IgE receptor (Fc[epsilon]RI) internalization suggesting a proximal role of RabGEF1 in regulating mast cell signaling events. To dissect the roles of RabGEF1 and its domains in regulating mast cell biology we lentivirally expressed a panel of RabGEF1 mutants in RabGEF1-/- mast cells. We found that RabGEF1 (1) harbors ubiquitin (Ub) ligase activity within an N-terminal A20 zinc finger domain, (2) binds to Ub and localizes to membranes through amino acids 1-150, (3) interacts with Rabaptin-5, a Rab5 effector, through a C-terminal coiled coil (CC) domain and, (4) activates Rab5 with a central VPS9 domain. Despite containing a number of domains, only the VPS9 was crucial to restore wildtype activation of RabGEF1-/- cells after IgE+Ag stimulation. Moreover, lack of the VPS9 or CC domain diminished Rabaptin-5 levels and reduced surface Fc[epsilon]RI and [beta]1 expression on mast cells suggesting that these domains are important for receptor homeostasis. Using shRNA knockdown of Rabaptin-5 we identified a novel role for Rabaptin-5 in maintaining Fc[epsilon]RI and [beta]1 surface expression by increasing surface stability and receptor half-life. The reduced Fc[epsilon]RI and [beta]1 surface levels in Rabaptin-5 deficient cells attenuated sensitivity to antigen induced adhesion, migration, and cytokine production in these cells. Despite Rabaptin-5's in vitro documented role as a Rab5 effector, Rab5 dependant processes (i.e., receptor internalization or endosome fusion) were unaffected by Rabaptin-5 deficiency and challenge the current thoughts of Rab5 processes in intact cells. These data show the importance of receptor trafficking in regulating mast cell activation.

Keywords: Immunology.
Advisor: Galli Stephen J. primary advisor. Thesis advisor
Meyer Tobias advisor. Thesis advisor
Nusse Roel
Utz Paul advisor. Thesis advisor
Regulation of motility in helicobacter pylori and the epsilon proteobacteria [electronic resource]

Microbes can colonize harsh and dynamic environments. Often, this ability depends on rapid responses through directed motility. Members of the Epsilon proteobacteria are found in many 'extreme' environments, including the human stomach1. We discovered that Helicobacter pylori establish bacterial colonies deep in the gastric glands, and identified a novel protein, ChePep, necessary to colonize this niche. By tracking the movement of single bacteria we found that mutants lacking ChePep cannot control the rotation of their flagella and swim with abnormally frequent reversals and even sustain bursts of movement backwards. Genetic experiments show that ChePep regulates flagellar rotation through the chemotaxis signaling system. By examining H. pylori within a microscopic pH gradient, we determined that ChePep is critical for normal chemotactic behavior. We expressed ChePep from the zoonotic pathogen Campylobacter jejuni, and the deep sea hydrothermal vent inhabitant Caminibacter mediatlanticus in H. pylori and found that ChePep is functionally conserved across the [Epsilon]-proteobacteria. ChePep represents a new family of chemotaxis regulators unique to the [Epsilon]-proteobacteria, and illustrates the differing strategies that microbes have evolved to control motility.

Keywords: Microbiology and Immunology
Advisor: Amieva Manuel
Falkow Stanley advisor. Thesis advisor
Monack Denise M. advisor. Thesis advisor
Schoolnik Gary K. advisor. Thesis advisor
Spormann Alfred M. advisor. Thesis advisor
Regulation of neuronal survival and CREB-dependent transcription by CaV1.2 L-type calcium channels [electronic resource]

Electrical activity is a potent trophic factor that promotes the survival of many populations of neurons. L-type calcium channels (LTCs) are particularly effective at promoting survival of neurons during development, in part by activating transcription factors such as CREB. Mutation of the LTC CaV1.2 causes Timothy Syndrome (TS), a disorder characterized by cardiac arrhythmias, webbing of fingers and toes, and autism. The TS mutation leads to loss of voltage-dependent inactivation (VDI) of the channel. Although it is known that VDI is critical for the transition between the open and resting states of the channel, the role that channel inactivation plays in cell signaling and neuronal development is poorly understood. The work in this dissertation shows that the TS mutation impairs CaV1.2-dependent neuronal survival and prevents activation of the transcription factor CREB. By using TS channels that contain pore mutations that prevent Ca2+ flux, we found that the ability of TS channels to cause apoptosis is independent of Ca2+ flux through the channel. Conversely, a novel leucine to proline mutation at position 1368 restores VDI to TS channels and prevents TS-dependent apoptosis and inhibition of CREB. These findings support the idea that CaV1.2 conveys two signals that together regulate activity-dependent neuronal survival and activation of CREB: a signal that depends on the channel conformation and a signal that depends on calcium influx through the channel. These results provide new insights into the mechanisms by which the L-type calcium channels activate transcription and regulate neuronal survival during development.

Keywords: Neurosciences.
Advisor: Dolmetsch Ricardo E. primary advisor. Thesis advisor
Goodman Miriam Beth advisor. Thesis advisor
McConnell Susan K. advisor. Thesis advisor
Scott Matthew P. advisor. Thesis advisor
The regulation of p53 function by lysine methylation [electronic resource]

The human p53 tumor suppressor is the most widely studied gene and protein in cellular biology. An open question in the field relates to the regulatory mechanism(s) that manage the complex functions of an essential tumor suppressor protein. Recently, a number of the protein lysine methyltrasferases (PKMTs) that mediate histone lysine methylation have also been identified as having activity on non-histone substrates. Reversible covalent methylation of lysine residues on histone or non-histone proteins constitutes a principal molecular mechanism that guides substrate proteins to diverse biological outcomes. The goal of this work was to 1) expand the understanding of lysine methylation and methyllysine recognition in the context of non-histone tumor suppressor proteins, and 2) elucidate the molecular mechanisms of such events. A handful of studies characterizing lysine methyation events on four distinct lysines in the C-terminal regulatory region of p53, have lead to the emergence of p53 as a model for non-histone lysine methylation. We contributed to this body of work by demonstrating that the lysine methyltransferase enzyme SET8/PR-Set7 is a novel regulator of p53. SET8 monomethylates p53 at lysine 382 (p53K382me1), resulting in reduced transactivation of highly responsive target genes. We used biochemical and crystallographic studies to identify the triple malignant brain tumor (MBT) domain containing chromatin compaction factor L3MBTL1 as the second know p53-effector protein. We demonstrated that SET8-mediated methylation of p53 at K382 promotes the interaction between L3MBTL1 and p53 in cells, and the chromatin occupancy of L3MBTL1 at p53 target promoters, thus providing a molecular explanation for the mechanism by which p53K382me1 is transduced to regulate p53 activity. Additionally we demonstrated that retinoblastomal tumor suppressor (RB) can be mono-methylated in vivo by SMYD2 at lysine 860, and that this methylation provides a direct binding site for L3MBTL1, helping to guide its functions in mammalian cells. In summary, we identified SET8 as a novel p53-modifying enzyme that mediates the regulatory post-translational modification at lysine 382; and, we identified L3MBTL1 a novel methyllysine effector protein for that mark. In a collaborative study we demonstrated that methylation of RB by Smyd2 promotes interaction with L3MBTL1. Together these results suggest that regulation by lysine methylation represents a broader paradigm for modulation of non-histone protein activity.

Keywords: Biology.
Advisor: Gozani Or Pinchas primary advisor. Thesis advisor
Chua Katrin Faye advisor. Thesis advisor
Lipsick Joseph Steven