VictorJuiz/thesis huggingface dataset:
The Dynamic Effects of Educational Accountability

Holding educators more accountable for the academic achievement of their students has been a central feature of recent education reforms. In several prominent instances, accountability schemes have set pecuniary performance targets that condition on prior scores as a means of controlling for student heterogeneity. Yet doing so introduces a potential dynamic distortion in incentives: teachers may be less responsive to the reform today in an effort to avoid more onerous targets in future — an instance of the so-called `ratchet effect.' The main chapters of this thesis consider possible dynamic distortions from three distinct but related vantage points. Chapter 2 builds a theoretical foundation for understanding the origin of ratchet effects in an educational context. Given an environment where school-level targets depend on student prior scores, I show that such dynamic gaming behaviour depends crucially on variation in the grade horizon of students, with teachers distorting their effort less when their decision affects fewer future scores within the same school. Chapter 3 analyzes the ratchet effect from an empirical perspective. Making use of rich educational panel data from North Carolina, I exploit variation in the grade span of schools to identify ratchet effects, finding compelling evidence of dynamic distortions using a difference-in-differences approach. I then directly estimate the structural parameters of the corresponding model, allowing for complementarities in production between teacher effort and student ability. Using these estimates, the grade five score in K-5 schools would be about 1.25 standard deviations lower under a counterfactual setting without any accountability scheme and 4.6% of a standard deviation higher if ratchet effects were eliminated via a prescribed reduction in each school's incentive target. Chapter 4 explores a potentially important class of mechanisms through which the identified dynamic effects might arise. In particular, school principals may re-allocate teachers across classrooms differentially by grade. By examining the yearly change in teacher assignments to tested subjects, I find evidence that principals re-sort higher quality teachers to higher grades and focus more costly re-sorting on lower grades in response to the reform, which is consistent with the overarching dynamic objective and results of the prior chapter.

Keywords: Dynamic gaming
Dynamic incentives
Ratchet effects
Education production
Educational accountability
Economics of Education
Advisor: McMillan, Robert
Closed-loop Control of Electrically Stimulated Skeletal Muscle Contractions

More than one million people are living with spinal cord injury (SCI) in North America alone. Restoring lost motor function can alleviate SCI-related health problems, as well as markedly increase the quality of life enjoyed by individuals with SCI. Functional electrical stimulation (FES) can replace motor function in individuals with SCI by using short electrical pulses to generate contractions in paralyzed muscles. A wide range of FES applications have been proposed, but few application are actually available for community use by SCI consumers. A major factor contributing to this shortage of real-world FES applications is the lack of a feasible closed-loop control algorithm. The purpose of this thesis is to develop a closed-loop control algorithm that is suitable for use in practical FES applications. This thesis consists of three separate studies. The first study examined existing closed-loop control algorithms for FES applications, and showed that a method of testing FES control algorithms under realistic conditions is needed to evaluate their likely real-world performance. The second study provided such a testing method by developing a non-idealities block that can be used to modify the nominal response of electrically stimulated muscle in simulations of FES applications. Fatigue, muscle spasm, and tremor non-idealities are included in the block, which allows the user to specify the severity level for each type of non-ideal behaviour. This nonidealities block was tested in a simulation of electrically induced knee extension against gravity, and showed that the nominal performance of the controllers was substantially better than their performance in the realistic case that included the non-idealities model. The third study concerned the development and testing of a novel observer-based sliding mode control (SMC) algorithm that is suitable for use in real-world FES applications. This algorithm incorporated a fatigue minimization objective as well as co-contraction of the antagonist muscle group to cause the joint stiffness to track a desired value. The SMC algorithm was tested in a simulation of FES-based quiet standing, and the non-idealities block was used to determine the probable performance of the controller in the real world. This novel controller performed very well in simulation, and would be suitable for use in selected practical FES applications. The work contained in this thesis can easily be extended to a wide range of FES applications. This work represents a significant step forward in closed-loop control for FES applications, and will facilitate the development of sophisticated new electrical stimulation systems for use by consumers in their homes and communities.

Keywords: functional electrical stimulation
spinal cord injury
closed-loop control
Advisor: Popovic, Milos R.
Enhancing the Nitrite Reductase Activity of Modified Hemoglobin: Bis-tetramers and their PEGylated Derivatives

The need for an alternative to red cells in transfusions has led to the creation of hemoglobin-based oxygen carriers (HBOCs). However, evaluations of all products tested in clinical trials have noted cardiovascular complications, raising questions about their safety that led to the abandonment of all those products. It has been considered that the adverse side effects come from the scavenging of the vasodilator – nitric oxide (NO) by the deoxyheme sites of the hemoglobin derivatives. Another observation is that HBOCs with lower oxygen affinity than red cells release oxygen prematurely in arterioles, triggering an unwanted homeostatic response. Since the need for such a product remains critical, it is important to understand the reactivity patterns that contribute to the observed complications. Various alterations of the protein have been attempted in order to reduce HBOC-induced vasoconstriction. Recent reports suggest that a safe and effective product should be pure, homogenous and have a high molecular weight along with appropriate oxygenation properties. While these properties are clearly important, vasodilatory features of hemoglobin through its nitrite reductase activity may also act as an in situ source of NO. It follows that HBOCs with an enhanced ability to produce NO from endogenous nitrite may serve to counteract vasoactivity associated with NO-scavenging by hemoglobin. Here we characterize the effects of different protein modifications on the nitrite reductase activity of hemoglobin. We produced a variety of HBOCs that include cross-linked tetramers, polyethylene glycol (PEG) conjugates and bis-tetramers of hemoglobin. We report that the rate of NO production strongly depends on the conformational state of the protein, with R-state stabilized proteins (PEG-Hbs), exhibiting the fastest rates. In particular, we found that PEGylated bis-tetramers of hemoglobin (BT-PEG) exhibit increased nitrite reductase activity while retaining cooperativity and stability. Animal studies of BT-PEG demonstrated that this material is benign: it did not cause significant increases in systemic blood pressure in mice, the major side effect associated with existing HBOCs. BT-PEG exhibits an enhanced nitrite reductase activity together with sample purity and homogeneity, molecular size and shape, and appropriate oxygenation properties, characteristics of a clinically useful HBOC.

Keywords: Hemoglobin
Blood substitutes
Kinetic reactions
Nitrite Reductase Activity
Protein Modification
Deconvolution
Advisor: Kluger, Ronald
The Power of Uncertainty: Algorithmic Mechanism Design in Settings of Incomplete Information

The field of algorithmic mechanism design is concerned with the design of computationally efficient algorithms for use when inputs are provided by rational agents, who may misreport their private values in order to strategically manipulate the algorithm for their own benefit. We revisit classic problems in this field by considering settings of incomplete information, where the players' private values are drawn from publicly-known distributions. Such Bayesian models of partial information are common in economics, but have been largely unexplored by the computer science community. In the first part of this thesis we show that, for a very broad class of single-parameter problems, any computationally efficient algorithm can be converted without loss into a mechanism that is truthful in the Bayesian sense of partial information. That is, we exhibit a transformation that generates mechanisms for which it is in each agent's best (expected) interest to refrain from strategic manipulation. The problem of constructing mechanisms for use by rational agents therefore reduces to the design of approximation algorithms without consideration of game-theoretic issues. We furthermore prove that no such general transformation is possible if we require mechanisms that are truthful in the stronger non-Bayesian sense of dominant strategies. In the second part of the thesis we study simple greedy methods for resolving complex auctions. We show that while such greedy algorithms are not truthful, they suffer very little loss in worst-case performance bounds when agents apply strategies at equilibrium, even in settings of partial information. Our analysis applies to various different equilibrium concepts, including Bayes-Nash equilibrium, regret-minimizing strategies, and asynchronous best-response dynamics. Thus, even though greedy auctions are not truthful, they may be appropriate for use as mechanisms under the goal of achieving high social efficiency at equilibrium. Moreover, we prove that no algorithm in a broad class of greedy-like methods can be used to create a deterministic truthful mechanism while retaining a non-trivial approximation to the optimal social welfare. Our overall conclusion is that while full-information models of agent rationality currently dominate the algorithmic mechanism design literature, a relaxation to settings of partial information is well-motivated and provides additional power in solving central problems in the field.

Keywords: Algorithmic game theory
Mechanism design
Auctions
Algorithms
Advisor: Borodin, Allan
Molloy, Michael
The Effects of Early Social Deprivation on Appetitive Motivation in Rats

Social interactions in early life influence the organization of neural and behavioural systems of developing mammalian young. Deprivation of social interactions with the primary caregiver and other immediate conspecifics (early social deprivation) has lasting consequences on behavioural functioning in later life. The purpose of this thesis was to investigate how early social deprivation affects the motivational aspects of behaviour in the context of appetitive stimuli. Rats were reared in complete isolation from the mother and litter using the method of artificial rearing (AR). Control rats were maternally reared (MR). In adulthood, rats were tested in a series of behavioural paradigms designed to assess the motivational impact of primary food reward and reward-related cues on food-seeking behaviour. AR increased the behavioural responsiveness of rats to the motivational impact of reward-related cues, but not to primary rewards themselves. Specifically, there were no significant effects of AR on food consumption or goal-directed instrumental responding for food. However, AR enhanced instrumental responding triggered by a previously conditioned reward cue. AR also increased the expression of approach behaviour towards a localizable conditioned reward cue and instrumental responding when the same cue was used as a reinforcer. An assessment of the mediating factors during development revealed that the lack of tactile stimulation normally received from the mother, but not sustained exposure to the stress hormone corticosterone, contributed to the long-term effects of AR. These findings represent a potential link between early-life social adversity and vulnerability to the development of problems with behavioural inhibition and attention in the presence of appetitive environmental cues.

Keywords: social deprivation
motivation
artificial rearing
behavioural inhibition
Advisor: Kraemer, Gary
The Politics of Security and the Art of Judgment in the Writings of Herman Melville and Janet Frame

This dissertation pairs a nineteenth-century American writer, Herman Melville, and a twentieth-century New Zealand writer, Janet Frame, to consider points of overlap between two novelists who were unusually sensitive to the problem of political thinking and decision in situations of state emergency. Consisting of three chapters on Melville’s later maritime fiction (Moby-Dick, Benito Cereno, and Billy Budd, Sailor) and two interleaving chapters on Frame’s late autobiographical and fictional writings (An Angel at My Table and The Carpathians), the dissertation explores how, in the work of these writers, figural work builds around interlinked questions of emergency and judgment. Both writers are interested in situations of peril when the fragility of bodily life is exposed and when the coherence of given political orders is tested. Both probe the response of the human legislative urge and the limits of the power of judgment in the time of crisis and exception, producing narratives of the tense moment of executive decision. Their literary forms heighten awareness of the mechanisms, frameworks, and effects of different modes of judgment--whether cognitive, moral, legal, aesthetic, or political--under emergency conditions. Out of this engagement with the nexus of judgment and security, both writers ask what might happen if we were to abide with precariousness and insecurity rather than default to the often destructive praxis of security. Melville and Frame also push the capacities of language and form in their attempt to represent the possibility of modes of judgment adequate to such political renewal. In their rhetoric and formal structures--including their experimental “disfiguration” of narrative lines--and in their creation of intricate, reflexive literary voices, these writers imagine what it would mean to come up against the limit of, and even to overturn, accepted categories of knowledge and thought, of calculation and judgment.

Keywords: American literature
New Zealand literature
Herman Melville (1819-1891)
Janet Frame (1924-2004)
American politics
sovereignty
security
Advisor: Downes, Paul
Characterization of the Adaptor Protein XB130, a Tyrosine Kinase Substrate and a Novel Component of the Lamellipodia

Adaptor proteins play a vital role in the propagation of cellular signals. Although they lack endogenous catalytic activity, they contain a variety of protein binding modules, which enable them to promote specific and efficient interactions with their binding partners. They form integrative platforms for a variety of molecules (e.g. lipids, tyrosine kinases, cytoskeletal and signaling proteins), and thereby link and coordinate key functions such as cell growth, motility and shape determination. Our laboratory has recently cloned a novel, 130 kDa adaptor protein, named XB130, as a structural homolog of actin-filament-associated-protein (AFAP-110), a stress fiber-binding Src substrate. However, the molecular interactions and functions of this novel adaptor remained to be elucidated. To characterize the function of XB130 we asked two general questions: (1) Is XB130 involved in the signal transduction pathways of tyrosine kinases? And (2) Is XB130 capable of regulating the cytoskeleton and/or is it regulated by the cytoskeleton? To address these questions first we investigated the tissue distribution of XB130 and discovered that it is abundantly expressed in thyroid. Therefore we asked whether it is a target of the thyroid-specific tyrosine kinase, RET/PTC, a genetically rearranged, constitutively active enzyme that plays a pathogenic role in papillary thyroid cancer. We found that XB130 is a RET/PTC substrate that couples RET/PTC signaling to phosphatidylinositol 3-kinase (PI3K) activation through its phosphorylation dependent interaction with the regulatory subunit p85 of PI3K. XB130 plays an important role in PI3K signaling, as downregulation of XB130 in TPC1 papillary thyroid cancer cells, harboring the RET/PTC1 kinase, strongly reduced Akt activity and concomitantly inhibited cell cycle progression and survival in suspension. In the second part we demonstrate that XB130 is a novel Rac- and cytoskeleton-regulated protein that exhibits high affinity to lamellipodial (branched) F-actin and impacts motility and invasiveness of tumor cells. In conclusion, my work characterized a novel adaptor protein and assigned two well-defined pathophysiological functions to it in the context of thyroid cancer cells.

Keywords: adaptor protein
tyrosine kinase
RET/PTC
PI3K
XB130
AFAP1L2
cytoskeleton
lamellipodia
papillary thyroid cancer
Advisor: Liu, Mingyao
Creating Controversy: Science Writers, Corporate Funders, and Non-expert Scientists in the Debate over Prions (1982-1997)

Stanley Prusiner’s proposal that a protein, the prion, was the infectious agent of transmissible spongiform encephalopathies (TSEs) created a great deal of interest, and discussion was not limited to the TSE research field. In fact, Prusiner actively appealed to individuals outside the TSE research field, particularly science writers, corporate funders, and scientists in other research areas. These individuals, in turn, provided Prusiner with the resources, publicity, and expertise to undertake his innovative research program. Prusiner’s emphasis on the revolutionary nature of prion and his claim that prion research could shed light on more common diseases fostered media interest and corporate support. Early newspaper reports stressed Prusiner’s interpretation of experimental results and helped to keep the idea of a protein agent alive until more evidence could be amassed. Corporate funders, with the aid of non-expert scientists, provided Prusiner with the means to carry out expensive, novel experiments and with the opportunity to collaborate with renowned researchers. Prusiner and his supporters were also adept at communicating the protein-only theory and were able to mitigate the impact of specialist criticism. They conceptualized prion protein conversion by using metaphors and analogies and by arguing that parallel phenomena already occurred in Nature. This shifted the discussion away from the problem of replication and recast the search for the TSE agent as a biochemical puzzle. These conceptualizations also enabled Prusiner to engage scientists in other fields, thereby turning his research program into an interdisciplinary enterprise. Moreover, the BSE crisis and Prusiner’s Nobel Prize provided opportunities to further discussion of prions to a wider audience. The engagement of non-experts ultimately created a vast and stable network of interested parties and supporters that was crucial to Prusiner’s success and to the acceptance of the protein-only theory.

Keywords: prions
science controversies
protein-only theory
prion theory
Advisor: Mazumdar, Pauline M. H.
Structural and Biophysical Characterization of Tumor Suppressor p53-interacting Proteins

The p53 protein is a critical tumor suppressor that is mutated in over half of all human cancers. It plays essential roles in maintaining genomic integrity by modulating the cellular response to various types of genotoxic stress. Associating with over 270 proteins to date, one of the mechanisms pivotal to p53’s multifaceted activities is protein-protein interactions. As to how most of these molecules bind to and affect p53 function remains unclear. Here we present a combined structural and biophysical approach to study three p53-interacting partners: BRCA1, IFI16 and p53 affinity reagent in an attempt to elucidate the basis of how these proteins recognize, bind to and alter p53’s biochemical functions. We have biophysically characterized the central region of BRCA1 and examined how it acts as a disordered scaffold to mediate association with p53 and other proteins. Having a putative role as a tumor suppressor, we have determined the crystal structures of the HIN-A and HIN-B domains of IFI16 and find that they interact with the C-terminus and DNA-binding core domain of p53, respectively, and enhance the DNA binding and transactivation activities of p53. Most cancer hot spot mutations of p53 are localized in the core domain and are thermally destabilized. Attaining molecules that stabilize the p53 fold has therefore been regarded as an attractive approach for cancer therapy. Lastly, using a phage-displayed library, evidence is presented to demonstrate a proof-of-principle for generating synthetic affinity reagents to potentially restore the function of tumor-derived p53 core domain mutants.

Keywords: p53
protein-protein interaction
structural biology
Advisor: Arrowsmith, Cheryl
Model Selection via Minimum Description Length

The minimum description length (MDL) principle originated from data compression literature and has been considered for deriving statistical model selection procedures. Most existing methods utilizing the MDL principle focus on models consisting of independent data, particularly in the context of linear regression. The data considered in this thesis are in the form of repeated measurements, and the exploration of MDL principle begins with classical linear mixed-effects models. We distinct two kinds of research focuses: one concerns the population parameters and the other concerns the cluster/subject parameters. When the research interest is on the population level, we propose a class of MDL procedures which incorporate the dependence structure within individual or cluster with data-adaptive penalties and enjoy the advantages of Bayesian information criteria. When the number of covariates is large, the penalty term is adjusted by data-adaptive structure to diminish the under selection issue in BIC and try to mimic the behaviour of AIC. Theoretical justifications are provided from both data compression and statistical perspectives. Extensions to categorical response modelled by generalized estimating equations and functional data modelled by functional principle components are illustrated. When the interest is on the cluster level, we use group LASSO to set up a class of candidate models. Then we derive a MDL criterion for this LASSO technique in a group manner to selection the final model via the tuning parameters. Extensive numerical experiments are conducted to demonstrate the usefulness of the proposed MDL procedures on both population level and cluster level.

Keywords: Minimum description length
Model selection
AIC
BIC
Data compression
Linear mixed effects
Generalized estimating equation
Functional data
Advisor: Yao, Fang
Craiu, Radu V.