VictorJuiz/thesis huggingface dataset:
Identifying the function for a conserved region on the surface of calcineurin
Keywords:  Department of Biology
Biology
calcineurin
calcium
dephosphorylation
Thesis

Calcineurin is a conserved Ca2+/calmodulin-activated phosphatase that plays a crucial role in many signaling pathways in both mammals and yeast. In mammals, calcineurin plays a role in T-cell activation, cardiac hypertrophy, and neuronal development. The widely used FDA-approved immunosuppressants cyclosporin A and FK506 both inhibit calcineurin, yet are associated with various side effects. Calcineurin is a heterodimer consisting of a catalytic A subunit (CNA) and a regulatory B subunit (CNB). When Ca2+ binds to the B subunit and the Ca2+-calmodulin complex binds to the A subunit, a conformational change causes the auto-inhibitory domain (AID) to be removed from the active site, allowing access to substrates. While some substrate interaction sites have been identified and well characterized, there is evidence that more sites may exist. A bioinformatics approach was used to identify conserved regions on the surface of calcineurin.

This research aims to elucidate the function of one such conserved surface region. Site-directed mutagenesis was used to replace conserved amino acids on CNA to alanine, a non-interacting amino acid, creating two mutants: CNA(N287A) and CNA(C292A, F294A). Calcineurin’s high degree of evolutionary conservation permits the study of the protein in S. cerevisiae (baker’s yeast). In vivo and in vitro assays were used to measure calcineurin-dependent transcription and dephosphorylation. None of the mutations led to decreased protein expression compared to wild-type calcineurin. Results showed that CNA(N287A) has increased activity in vivo, while decreased activity in vitro, and CNA(C292A, F294A) has decreased activity both in vivo and in vitro. While it is currently not understood why there is a discrepancy between the results for CNA(N287A), this project shows that the conserved region defined by these residues allosterically affects enzymatic activity. Experiments are already underway to determine if this region is also implicated in calcineurin activation through an AID-dependent mechanism.
Understanding how calcineurin is activated and regulated provides valuable information for studying the various pathways in which it is a part of. Furthermore, learning more about calcineurin’s structure provides vital information for better drug design.
Ideological sorting and the transformation of American politics [electronic resource]
Keywords: Political Science.

This dissertation explores how American politics entered the current era where it is characterized by close electoral competition between two increasingly polarized political parties. The first and second chapters of the dissertation examine how the changing party identification of the American electorate led to close competition in congressional elections, which had been dominated by the Democratic Party from the 1930s through the 1980s. The first chapter applies a Bayesian changepoint model to identify periods where the macropartisanship of the American public (measured by Gallup surveys from 1950 to 2011) underwent major equilibrium shifts. The model identifies two distinct regimes of American politics, from 1950 to 1983 and 1983 to the present, puncuated by a large decrease in Democratic macropartisanship. The second chapter considers the sources of the equilibrium shift in party identification that was identified in the first chapter and how this equilibrium shift changed the balance of power in elections. Democrats enjoyed a large advantage in party identification until conservative Democrats (both in the South and non-South) shifted out of the party during the 1980s. The Democrats' long standing advantage in party identification had given them a major advantage in House elections and the loss of this advantage made Republicans competitive in congressional elections for the first time since the 1920s. The third chapter examines the electoral incentives for congressional polarization, studying how the ideological extremism of House incumbents has affected their probability of losing during the 20th and early 21st centuries. This chapter shows that incumbents tended to face a higher penalty for extremism during periods of low polarization, so increasing polarization has not hurt the ability of incumbents to win re-election.
Imaging of ultrafast phase separation in magnetite and spin injection into copper [electronic resource]
Keywords: Materials Science and Engineering.

In the recent years, there has been a renewed interest in magnetic materials and correlated oxides due to major advance in thin-film growth technology. Materials showing metal insulator transition with orders of magnitude drop in conductivity, have become a potential candidate for novel electronics and photonics devices. While in data storage, the discovery of Giant Magnetoresistance (GMR) effect has revolutionized read head technology of the hard disk drives. The subsequent investigation of the Spin Transfer Torque phenomenon, promises to be a good candidate for Magnetic Random Access Memory devices. In the first part of my thesis project I focused on the metal insulator transition (Verwey transition) in magnetite triggered by optical excitation. Magnetite, is the first oxide where a relationship between electrical conductivity and fluctuating/localized charges was observed, with a drop in conductivity by two orders of magnitude at 123 K. The Verwey transition is also accompanied by a structural change from monoclinic to cubic symmetry. Recently, three-Fe-site lattice distortions called trimerons have been identified as the true microscopic face of electronic order in low temperature insulating phase. I studied the real time response of insulating magnetite to optical excitation with ultrafast soft X-ray scattering as well as optical pump probe experiments and discovered this to be a two-step process. After an initial femtosecond (300 fs) destruction of individual trimerons in the corresponding lattice, a phase separation into residual insulating trimeron and cubic metallic phases on a 1.5 picosecond timescale is observed. The second part of my thesis project involves understanding spin transport phenomena in spin transfer torque devices with a focus on ferromagnet-paramagnet interface. It has been predicted that near such an interface Copper develops a small nonequilibrium magnetization due to spin accumulation. I use x-ray magnetic circular dichroism to determine the magnitude and the sign of this transient magnetization in Copper. As the induced magnetization is extremely small, I employ time resolved x-ray microscopy to modulate the current on/off signal at MHz rates. Using this technique we have directly imaged the transient magnetization in Copper for the very first time and deduced its magnitude and sign.
Imaging Redshift Estimates for Fermi BL Lacs
Keywords:  Department of Physics
BL Lac
Thesis

We have measured i images of BL Lacertae objects (BL Lacs) to detect or constrain the flux of the host galaxy. Under common standard candle assumptions these data provide estimates of, or lower bounds on, the redshift. Our targets are a set of flat-spectrum radio counterparts of high flux Fermi Large Area Telescope (LAT) sources, with deep spectral observations showing them to be continuum-dominated BL Lacs. In this sample, 6 of 11 BL Lacs yielded significant host detections, with standard candle redshifts z=0.13-0.58. Our estimates and lower bounds are generally in good agreement with other redshifts estimates for these sources.
Imaging with multiples by least-squares reverse time migration [electronic resource]
Keywords: Ronen, Shuki.
Geophysics.

This dissertation presents a novel technique for using surface-related multiples to improve imaging in geologically complex areas. It overcomes a challenge of the migration-based approach where crosstalk artifacts appear in the image. In the case of reverse-time migration, these imaging artifacts are the result of cross-correlation between wrong pairs of incident and scattered wavefields. Joint least-squares reverse-time migration, also known as linearized inversion, can coherently focus the reflection energy of primary and surface-related multiples into one image. By posing the imaging problem as an inversion problem, spurious reflectors or noises in the image can be attenuated. In geologically complex areas that contain salt structures, the proposed method not only improves the imaging but also added additional angular coverage in poorly illuminated areas. With respect to improving subsurface illumination, it is particularly advantageous to apply this method to ocean-bottom node acquisition. A modified modeling operator in the inversion process was introduced to model the surface-related multiples in the data. This modified modeling operator uses the data as an areal source, which removes the need to estimate the source wavelet. By using the data as a source, only the last down-going and up-going legs of the wavepath have dependency on the migration velocity model. As a result, this operator has the same sensitivity to the migration velocity model as the conventional primary modeling operator. From an imaging prospective, the robustness of the technique is improved when there are deviations between the migration velocity and the true velocity. The surface-related multiple operator can be combined with the conventional primary operator to form a joint operator that properly accounts for the physics of both primary and surface-related multiple reflections. Several methods are introduced to improve the convergence of least-squares reverse-time migration, particularly for areas with a complex salt structure. To emphasize the shadow zones in the image, a target-oriented data-reweighting scheme is incorporated in the inversion process. To extract the most information from the least-squares reverse-time migration algorithm, salt dimming data-weighting was introduced to down-weight the reflection energy coming from strong velocity contrasts in the migration velocity model. Such energy often dominates the inversion. When least-squares migration is extended to the angle domain, prestack extended-angle domain filtering can be incorporated into the modeling operator to remove unwanted noise in the image. Applications to synthetic and field ocean-bottom node datasets show that, compared to migration or single-mode inversion, joint least-squares reverse-time migration provides the best overall subsurface image and angular coverage. In particular, areas near and underneath a complex salt structure are better illuminated when surface-related multiples are used as signal.
The impact of campaign promises on voter behavior [electronic resource]
Keywords: Political Science.

How does a candidate's rhetoric affect a voter's understanding of the candidate's position? Campaign promises, specifically, seem like they would affect voter opinion differently than position statements made without a promise. This dissertation develops a theory of how promises affect voter opinions of candidates with regard to non-promise position statements. Specifically, I argue that promises serve as commitments to voters of an action the candidate will take on a specific issue when in office. By increasing their perceived commitment to an issue, promises alter voter opinions both prospectively and retrospectively. Through a descriptive study of promise-making throughout the televised, presidential election debates, I show that there is a distinction between promises and non-promise position-taking in actual campaigns. I then present data from several survey experiments that demonstrate that promises have an impact on voter evaluations of candidates, and how they affect voter opinions. Ultimately, this dissertation points to the importance of understanding political rhetoric in position-taking.
Impact of nominal signal deformations on satellite navigation systems [electronic resource]
Keywords: Electrical Engineering.

Global Navigation Satellite Systems (GNSS), of which GPS is the standard-bearer, are ubiquitous and widely used in various applications including aviation, agriculture, automobile navigation, search and rescue, and recreation. GNSS are steadily being improved with the addition of new constellations, new frequencies, and new signals. Future multi-frequency GNSS will eliminate one of the largest error sources (ionosphere) and promises even better performance: improving accuracy from approximately 5 meters to 1 meter. Unfortunately, the new frequencies and signals will have small but unavoidable biases relative to one another. The impact of these biases increases as other error sources are eliminated. Nominal satellite signal deformations -- deviations of broadcast GPS satellite signals from ideal -- result in tracking errors, range biases, and position errors in GPS receivers. It is thus imperative that these errors are quantified, to enable the design of appropriate error budgets and mitigation strategies for various application fields. Traditional measurement methods for these signal deformations can be broadly classified into two categories. The first category uses large antenna dishes paired with high-resolution, high-bandwidth measurements and is limited to short time intervals (seconds) due to data storage constraints. However, these measurements could be subject to time-varying effects that are unobservable between data sets. The second category uses lower-resolution, lower bandwidth measurements over long continuous time periods, but less effectively attenuates error sources such as multipath that obscure the signal deformations of interest. The major contribution in this dissertation is the development of an innovative measurement method that combines the merits of both past approaches while mitigating the disadvantages, rendering nominal signal deformations measurable. Furthermore, these measurements were repeatable over long time periods of hours, days, and months. A good estimate of the position error impact on user receivers could be obtained using these highly consistent measurements. A mitigation strategy was developed in response and verified using this measurement method. The results show that the position error impact could be substantial, but could also be effectively mitigated with the use of an appropriate mitigation strategy. This work is a critical component toward the successful implementation of future dual-frequency GNSS-based landing systems for aviation.
The importance of linguistic and non-linguistic context in early language understanding and word learning [electronic resource]
Keywords: Psychology.

In this dissertation, I propose that some of the mechanisms used by adults to resolve ambiguity in sentence processing might also be exploited by children to interpret language and resolve referential ambiguity in word learning. I present the findings of four studies focusing on how young children make use of words other than labels (i.e., the semantic context of sentences) to help disambiguate the referent of familiar and novel words. In Study 1, 30-month-olds were able to use their knowledge about verbs and actions to rapidly determine the objects a speaker was talking about, even when these objects were unfamiliar. In addition to determining the objects being talked about, children took advantage of these opportunities to map two novel words to two unfamiliar objects, and they remembered these mapping for over a week. Moreover, children's memory for the object names was related both to their vocabulary skill and to their proficiency in establishing reference incrementally based on information at the verb. In Study 2, children used their knowledge about familiar objects and the locations in which they typically appear to rapidly establish reference. Children's proficiency in making this kind of inference was related to their vocabulary skills. In Study 3, children combined their knowledge about the names of locations and the names of objects to interpret complex spoken sentences, guiding their attention to an object even before it was named. Children's predictive listening was again related to their vocabulary skills. In Study 4, children used their knowledge about locations to rapidly guide their attention to objects in their environment, even when the objects were unfamiliar. And again, children took advantage of these opportunities to map novel words to the unfamiliar objects. As in Study 1, children's ability to remember the names of the unfamiliar objects was related to their proficiency in establishing reference based on the names of locations. These studies show that words other than object names can guide children's attention to familiar or novel objects, providing opportunities to create or strengthen connections between words and objects.
Improving fiber optic gyroscope performance using a single-frequency laser [electronic resource]
Keywords: Electrical Engineering.

The fiber optic gyroscope has become the most commercially successful fiber sensor to date and has been deployed in a variety of applications requiring high sensitivity, low noise measurements of rotation rate. Yet despite this success, traditional broadband source-driven gyroscopes have failed to reach their ultimate potential as the primary rotation sensors for inertial navigation applications -- such as guidance in airplanes and ships -- being passed over in favor of more costly and relatively more complicated technologies. Achieving the performance levels necessary for these demanding applications using a broadband source has proven challenging. To overcome these challenges, we propose a simple but significant alteration to the standard gyroscope configuration: replace the traditional broadband source with a single-frequency laser. While initial experimental work on fiber optic gyroscopes employed laser sources, researchers quickly abandoned this approach following the discovery that a broadband source could mitigate the deleterious effects of fiber backscattering, as well as polarization and nonlinear effects. As a result, a thorough analysis of these effects was never carried out. We present a more robust analysis with particular focus on backscattering and show that the induced noise and drift in a laser-driven gyroscope can meet navigation-grade requirements. Achieving this improvement requires careful selection of the laser linewidth and phase modulation scheme. These performance gains comes with the added benefit that a laser-driven gyroscope does not suffer from source beating noise and high scale factor instability, two limiting factors for broadband source-driven gyroscopes. We present experimental results that verify our theoretical predictions and compare the experimental performance of our laser-driven gyroscope with a broadband source-driven gyroscope.
Inclusive search strategies and bottom-up approaches for new physics at colliders [electronic resource]
Keywords: Physics.

The first run of the Large Hadron Collider (LHC) has strongly challenged our view of new physics by tightly constraining the most investigated scenarios such as super- symmetry. If new physics is within the reach of future experiments, discovering it will require devising new data analysis techniques and considering new approaches to open issues such as the fine-tuning problem. This thesis discusses how to elaborate new search strategies using signature-based --bottom-up-- approaches. It focuses in particular on multijet LHC signatures, the fine-tuning problem, dark matter detection and explaining non-standards Higgs couplings.
Inference and estimation in high-dimensional data analysis [electronic resource]
Keywords: Electrical Engineering.

Modern technologies generate vast amounts of fine-grained data at an unprecedented speed. Nowadays, high-dimensional data, where the number of variables is much larger than the sample size, occur in many applications, such as healthcare, social networks, and recommendation systems, among others. The ubiquitous interest in these applications has spurred remarkable progress in the area of high-dimensional data analysis in terms of point estimation and computation. However, one of the fundamental inference task, namely quantifying uncertainty or assessing statistical significance, is still in its infancy for such models. In the first part of this dissertation, we present efficient procedures and corresponding theory for constructing classical uncertainty measures like confidence intervals and p-values for single regression coefficients in high-dimensional settings. In the second part, we study the compressed sensing reconstruction problem, a well-known example of estimation in high-dimensional settings. We propose a new approach to this problem that is drastically different from the classical wisdom in this area. Our construction of the sensing matrix is inspired by the idea of spatial coupling in coding theory and similar ideas in statistical physics. For reconstruction, we use an approximate message passing algorithm. This is an iterative algorithm that takes advantage of the statistical properties of the problem to improve convergence rate. Finally, we prove that our method can effectively solve the reconstruction problem at (information-theoretically) optimal undersampling rate and show its robustness to measurement noise.
Inference for correlation-based hierarchical clustering of variables [electronic resource]
Keywords: Statistics.

In this dissertation, we consider the clustering of variables based on their pairwise absolute sample correlations, with a focus on hierarchical clustering procedures. While these procedures have existed for quite some time, statistical guarantees on the resulting clusters of variables are not available. We construct test statistics and corresponding null distributions for each merge in the clustering tree. We develop new multiple testing procedures to combine these stepwise results into an adaptive cutting procedure to select a set of clusters from the hierarchical tree and attach a statistical guarantee. As part of this work, we also develop new distributional results for the large order statistics of sample correlations between many spherically distributed variables.
The influence of convergent margin structure on deep-water stratigraphic architecture, pore pressure evolution, and source rock maturation in the East Coast Basin, New Zealand [electronic resource]
Keywords: Geological and Environmental Sciences.

The East Coast Basin of the North Island, New Zealand contains active petroleum systems and has been explored intermittently since the late 1800s. Despite a few small discoveries, the basin is non-commercial largely due to stratigraphic and structural complexities associated with its development on the Hikurangi convergent margin. The major petroleum system risks are the presence of reservoir rock and good potential, mature source rock. Additionally, high overpressures have caused significant drilling problems, representing both a financial burden and a safety hazard for exploration. This dissertation investigates the petroleum system elements and processes of the East Coast Basin, and outlines the importance of convergent margin structure on reservoir architecture, overpressure generation and distribution, and source rock maturation. Each of the three chapters addresses aspects of the petroleum system. Chapter 1 focuses on the reservoir rock though stratigraphic and architectural analysis of an outcropping deep-water turbidite deposit, representing a reservoir analog for the basin. Chapter 2 establishes the structural and stratigraphic framework for the basin through geologic time, providing a means to understand and predict the development of overpressure. Lastly, Chapter 3 assesses the source rock maturation in the East Coast Basin through evaluation of the paleo-basal heat flow and structurally-controlled burial history. This dissertation integrates data from a variety of disciplines (sedimentology, structure, geomechanics, geochemistry) and scales (well samples, well logs, outcrop, seismic data) in order to provide a robust basin analysis of the East Coast Basin.