VictorJuiz/thesis huggingface dataset:
A Randomized Double-blind Placebo-controlled Clinical Study Investigating Clinical Outcome and Gene Expression Responses to Insulin-enhanced Cardioplegia during Cardiac Surgery in Infants with Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect and infants with TOF incur significant right ventricular(RV) dysfunction due to perioperative injury. Insulin has been shown to reduce perioperative myocardial injury and significantly improve postoperative cardiac function. However, studies are limited to the adult population and the effects in a pediatric heart with a CHD are unknown. To the best of our knowledge, this is the first randomized, double blind, placebo-controlled clinical study designed to investigate insulin’s potential cardioprotective effects postoperatively and mechanisms of action during pediatric cardiac surgery. Thirty infants with TOF were equally randomly allocated to receive either standard cardioplegia (SC) or 10UI insulin-enhanced (IC). Expression profiles of surgery were generated from biopsies extracted from the right ventricular outflow tract (end ischemia and five minutes of reperfusion) and hybridized to Affymetrix HG-U133A GeneChips. Gene expression profiles were generated using two softwares, ArrayAssist V2.6 (paired t-test) and affylmGUI (ANOVA). Survival rate was 100%. Compared to patients in the SC group, patients in the IC group demonstrated a trend toward a 1.8 fold decrease (p = .06) in reperfusion duration (61.93 ± 61.12 vs. 35.20 ± 23.16 hrs., respectively), a significant 2-fold decrease in the length of ICU stay (p = .04) (4.2 ± 3.9 vs. 2.3 ± 1.1 days, respectively) and a trend toward a 2.5 fold decrease in intubation duration (p= .06) (2.5± 12.2 vs. 55.0 ± 67 hrs., respectively). Patients in the IC group also demonstrated significantly lower inotropic scores, calculated at 12-hour intervals across a 48-hour ICU period, (ANOVA p = .01) and significantly greater urine volume, by 71%, (p = .02). IC evoked a cardioprotective gene expression profile aimed at mitigating perioperative myocardial injury, specifically; apoptosis, inflammation, cardiac hypertrophy, arrythmias and fibrosis. The improved postoperative outcome and cardioprotective gene expression signature with IC suggests that, administration of insulin during cardiac surgery in infants with TOF may prevent cardiac dysfunction as a result of mitigating perioperative myocardial injury. Overall, this exploratory study demonstrated insulin-enhanced cardioplegia to be a potential cardioprotective agent during pediatric heart surgery.

Keywords: insulin
cardiac surgery
pediatric
gene expression
tetralogy of Fallot
Advisor: Coles, John
Valuing and Evaluating Evidence in Medicine

Medical decisions should be based on good evidence. But this does not mean that health care professionals should practice evidence-based medicine. This dissertation explores how these two positions come apart, why they come apart, and what we should do about it. I begin by answering the descriptive question, what are current standards of evidence in medicine? I then provide a detailed critique of these standards. Finally, I address the more difficult normative question, how should we determine standards of evidence in medicine? In medicine, standards of evidence have been established by the pervasive evidence-based medicine (EBM) movement. Until now, these standards have not been subjected to comprehensive philosophical scrutiny. I outline and defend a theory of knowledge – a version of Helen Longino’s Critical Contextual Empiricism (CCE) – which enables me to critically evaluate EBM. My version of CCE emphasizes the critical evaluation of background assumptions. In accordance with this, I identify and critically evaluate the three substantive assumptions underlying EBM. First, I argue that medicine should not be held to the restrictive definition of science assumed by proponents of EBM. Second, I argue that epidemiological evidence should not be the only “base” of medical decisions. Third, I argue that not only is the particular hierarchy of evidence assumed by EBM unjustified, but that any attempt to hierarchically rank research methods is incoherent and unjustifiably restricts medical knowledge. Current standards of evidence divert attention from many legitimate sources of evidence. This distorts medical research and practice. In the remainder of the dissertation I propose means for improving not only current standards of medical evidence but also the process of producing and defending future standards. On the basis of four CCE norms, I argue that we have reason to protect and promote those features of the medical community that facilitate diversity, transparency, and critical interaction. Only then can we ensure that the medical community retains its ability to produce evidence that is both rigorous and relevant to practice.

Keywords: Philosophy
Philosophy of Medicine
Social Epistemology
Evidence-based Medicine
Advisor: Morrison, Margaret
Hybrid Mobile Robot System: Interchanging Locomotion and Manipulation

This thesis presents a novel design paradigm of mobile robots: the Hybrid Mobile Robot system. It consists of a combination of parallel and serially connected links resulting in a hybrid mechanism that includes a mobile robot platform for locomotion and a manipulator arm for manipulation, both interchangeable functionally. All state-of-the-art mobile robots have a separate manipulator arm module attached on top of the mobile platform. The platform provides mobility and the arm provides manipulation. Unlike them, the new design has the ability to interchangeably provide locomotion and manipulation capability, both simultaneously. This was accomplished by integrating the locomotion platform and the manipulator arm as one entity rather than two separate and attached modules. The manipulator arm can be used as part of the locomotion platform and vice versa. This paradigm significantly enhances functionality. The new mechanical design was analyzed with a virtual prototype that was developed with MSC Adams Software. Simulations were used to study the robot’s enhanced mobility through animations of challenging tasks. Moreover, the simulations were used to select nominal robot parameters that would maximize the arm’s payload capacity, and provide for locomotion over unstructured terrains and obstacles, such as stairs, ditches and ramps. The hybrid mobile robot also includes a new control architecture based on embedded on-board wireless communication network between the robot’s links and modules such as the actuators and sensors. This results in a modular control architecture since no cable connections are used between the actuators and sensors in each of the robot links. This approach increases the functionality of the mobile robot also by providing continuous rotation of each link constituting the robot. The hybrid mobile robot’s novel locomotion and manipulation capabilities were successfully experimented using a complete physical prototype. The experiments provided test results that support the hypothesis on the qualitative and quantitative performance of the mobile robot in terms of its superior mobility, manipulation, dexterity, and ability to perform very challenging tasks. The robot was tested on an obstacle course consisting of various test rigs including man–made and natural obstructions that represent the natural environments the robot is expected to operate on.

Keywords: Mobile Robots
Teleoperation
Mechatronic Systems
Control System Design
Autonomous Navigation
Simulations & Animations
Prototype Development
Advisor: Goldenberg, Andrew A.
Zu, Jean W.
Analytic Modeling of Four-wave-mixing with Inter-channel Walk-off in Wavelength-division-multiplexed Optical Links

Fiber nonlinearity can cause interactions and crosstalk between co-propagating dense wavelength division multiplexed channels in high capacity optical fiber communication systems. The crosstalk between channels leads to degradation of the bit error performance of the system. One of the mechanisms of this crosstalk is Four-Wave-Mixing (FWM) caused by the fiber nonlinearity. It is important to have an analytic model for the FWM to estimate and minimize the impact of FWM for a given transmission system design. Conventional analytic models for FWM ignore the inter-channel walk-off effect. In this thesis a model for FWM is developed which rigorously accounts for the walk-off effect. The model is derived for degenerate and non-degenerate FWM. This model is derived for conventional RZ-OOK and the emerging RZ-DPSK modulation formats. A detailed physical understanding of the walk-off contribution to the FWM noise is developed. The first direct comparison, between an analytic model for FWM and split-step Fourier (SSF) simulations for the general case of random modulated channels is presented, for a single span 10-Gb/s link. It is shown that for both RZ-OOK and RZ-DPSK modulation formats the walk-off effect significantly increases the FWM noise variance for all FWM types before any filtering at the end of fiber. When a multiplexer/de-multiplexer is used the walk-off effect is significant and observable for the degenerate FWM case but is no longer significant for the non-degenerate FWM case. In the typical situation when a sub-bit-rate electrical low pass filter is also used, the walk-off effect is effectively removed for all three types of FWM. Comparing the models for the two modulation formats it is found that the FWM noise standard deviation and related BER penalty are much smaller for RZ-DPSK as compared to that for RZ-OOK at the same average launch power.

Keywords: WDM
FWM
Advisor: Pavel, Lacra
Human Brain Responses to Speech Sounds

Electrophysiologic responses are used to estimate hearing thresholds and fit hearing aids in young infants, but these estimates are not exact. An objective test of speech encoding could be used to validate infant fittings by showing that speech has been registered in the central auditory system. Such a test could also show the effects of auditory processing problems on the neural representation of speech. This thesis describes techniques for recording electrophysiologic responses to natural speech stimuli from the brainstem and auditory cortex. The first technique uses a Fourier analyzer to measure steady-state brainstem responses to periodicities and envelope changes in vowels, and the second uses a windowed cross-correlation procedure to measure cortical responses to the envelopes of sentences. Two studies were conducted with the Fourier analyzer. The first measured responses to natural vowels with steady and changing fundamentals, and changing formants. Significant responses to the fundamental were detected for all of the vowels, in all of the subjects, in 19 – 73 s (on average). The second study recorded responses to a vowel fundamental and harmonics. Vowels were presented in opposite polarities to distinguish envelope responses from responses to the spectrum. Significant envelope responses were detected in all subjects at the fundamental. Significant spectral responses were detected in most subjects at harmonics near formant peaks. The third study used cross-correlation to measure cortical responses to sentences. Significant envelope responses were detected to all sentences, at delays of roughly 180 ms. Responses were localized to the posterior auditory cortices. A model based on a series of overlapping transient responses to envelope changes could also account for the results, suggesting that the cortex either directly follows the speech envelope or consistently reacts to changes in this envelope. The strengths and weaknesses of both techniques are discussed in relation to their potential clinical applications.

Keywords: Evoked responses
Speech
Steady-state responses
Brainstem
Auditory cortex
Advisor: Picton, Terence W.
The L2 Acquisition and L1 Attrition of the Interpretation and Use of Aspectual Properties in Spanish among English-speaking L2 Learners and Long-term Spanish Immigrants

This thesis examines the L2 acquisition and L1 attrition of aspectual properties in Spanish. Specifically, it investigates preterite versus imperfect distinctions and the ongoing value of the Spanish present tense among English-speaking L2 learners and long-term Spanish immigrants. In contrast to previous research which explains L2 learners’ difficulties as a result of either maturational constraints or morphosyntactic development, this study provides a supplementary explanation focusing on L1 transfer of the semantic patterns of tense morphemes. The study proceeds by comparing data from L2 learners with that of long-term Spanish immigrants. Unlike what is argued for L2 acquisition difficulties, the difficulties immigrants may have with tense and aspect cannot stem solely from impairment reasons. These immigrants acquired the L2 as adults. Therefore, to the extent that L2 learners share similar patterns of errors with adult immigrants, L2 speakers’ difficulties cannot be unequivocally linked to causes related to impairment. Instead, following a selectional approach to aspectual variation (De Swart, 1998), it is argued that transfer of the selectional patterns of tense morphemes offers a more encompassing explanation of the difficulties L2 speakers face with tense and aspect. Data collection involved two truth-value judgment tasks, two acceptability judgment tasks and two elicited production tasks. Twenty long-term immigrants, twenty English-speaking L2 learners of Spanish, and twenty native speakers of Spanish serving as control participants took part in the study. Results show incorrect activation of aspectual patterns by both experimental groups and similar patterns of difficulties in some of the conditions under investigation. I conclude that transfer from the other language offers a more adequate explanation of the difficulties L2 learners face

Keywords: Second Language Acquisition/L1 Attrition
Spanish-English bilinguals, Tense and Aspect
Advisor: Perez-Leroux, Ana Teresa
Davidson on Conceptual Schemes

In his influential essay “On the Very Idea of a Conceptual Scheme”, Donald Davidson argues that we cannot make sense of conceptual relativism, the doctrine that there could be incommensurably different systems of concepts applicable to a single world. According to Davidson, there is no criterion of identity for language that does not imply or presuppose the possibility that we interpret that language by means of our own language. Given some plausible assumptions, this implies that there is at most one conceptual scheme, one way of interpreting or representing the world. But then the very idea of a conceptual scheme is empty. The dissertation is an examination of Davidson’s reasoning, and a defence of a different position regarding conceptual relativism. I reject much of Davidson’s argumentation, and his radical (subordinate) conclusion that we would be able, at least in principle, to make sense of any language. Languages that we would be unable to translate or interpret, even in principle, are at least logically possible, in my view. However, this possibility should not be thought to imply or encourage conceptual relativism. In this respect, I think that Davidson and many of his critics have conflated the notion of a difference in conceptual scheme, which requires incommensurability between languages or systems of concepts, and mere conceptual difference. I argue that a genuinely alternative conceptual scheme would be associated with language unintelligible to us because of its relation to our language. For what is at issue, supposedly, is a conceptual relation: a relation between languages, not a relation between speakers, or their capacities, on the one hand, and languages, on the other. I try to show how some of Davidson’s arguments, suitably modified, can be deployed against the possibility of an alternative scheme, so understood, and provide some additional arguments of my own. My position is thus significantly weaker than Davidson’s: there could not be languages that we would be unable to interpret because they are incommensurable with our own.

Keywords: Davidson
conceptual schemes
relativism
interpretation
Advisor: Katz, Bernard
Membrane Surface Charge and Lipid Signaling in Phagocytosis

Phagocytosis is an important component of innate and adaptive immunity. The formation of phagosomes and the subsequent maturation that capacitates them for pathogen elimination and antigen presentation are complex processes that involve signal transduction, cytoskeletal reorganization and membrane remodeling. Lipids are increasingly appreciated to play a crucial role in these events. Sphingolipids, cholesterol and glycerophospholipids, notably the phosphoinositides, are required for the segregation of signaling microdomains and for the generation of second messengers. They are also instrumental in the remodeling of the actin cytoskeleton and in directing membrane traffic. They accomplish these feats by congregating into liquid-ordered domains, by generating active metabolites that activate receptors and by recruiting and anchoring specific protein ligands to the membrane, often altering their conformation and catalytic activity. A less appreciated role of acidic phospholipids is their contribution to the negative surface charge of the inner leaflet of the plasmalemma. The unique negativity of the inner aspect of the plasma membrane serves to attract and anchor key signaling and effector molecules that are required to initiate phagosome formation. Conversely, the loss of charge that accompanies phospholipid metabolism as phagosomes seal facilitates the dissociation of proteins and the termination of signaling and cytoskeleton assembly. In this manner, lipids provide a binary electrostatic switch to control phagocytosis. Phosphatidylserine, an abundant but relatively little studied anionic phospholipid, is expected to contribute significantly to the surface charge of membranes. The development of a PS-specific biosensor revealed that this lipid is distributed to the cytosolic leaflet of the plasma membrane and of the membranes of the endocytic pathway. Consequently, the charge conferred by PS directs the targeting of proteins with cationic domains or polybasic clusters to these membrane compartments. PS is also present on the phagosome membrane and similarly helps to recruit cationic proteins to this organelle. The electrostatic switch theory as proposed by McLaughlin and Aderem provides a novel biophysical mechanism in which proteins can be regulated in cells, in parallel with the traditional biochemical mechanisms that regulate the activity and conformational status of proteins.

Keywords: cell biology
Advisor: Grinstein, Sergio
The Role of the N-Terminal Zinc Binding Domain of ClpX in Cofactor and Substrate Recognition

ClpX is an ATPase that belongs to a unique group of ATP-dependent chaperones supporting targeted protein unfolding and degradation in concert with their respective proteases. ClpX functions alone or in conjunction with a cylindrical serine protease ClpP. ClpX consists of an N-terminal domain and a C-terminal AAA+ ATP-binding domain. The chaperone oligomerizes into a hexamer with the AAA+ domains forming the base of the hexamer and the N-termini extending out of the base. Here we demonstrate that the N-terminal domain of ClpX is a C4-type zinc binding domain (ZBD) which forms a very stable dimer. ZBD is essential for promoting the degradation of some established ClpXP substrates such as lambdaO and MuA. Experiments indicate that ZBD contains a primary binding site for the lambdaO substrate and for the cofactor SspB. Furthermore, analysis of the binding preferences of the ZBD and AAA+ domains revealed that both domains preferentially bind to hydrophobic residues but have different sequence preferences, with the AAA+ domain preferentially recognizing a wider range of specific sequences than ZBD. As part of this analysis, the binding site of SspB on ZBD in ClpX was determined by NMR and mutational analysis. The SspB C-terminus was found to interact with a hydrophobic patch on the surface of ZBD. The affinity of SspB towards ZBD and the geometry of the SspB-ZBD complex were also investigated. Analysis of ClpX conformational changes during its functional cycle indicated that the ZBDs in ClpX undergo a large nucleotide-dependent block movement into the AAA+ ring. Hence, we propose that ClpX switches between a capture and a feeding conformation. Based on all of these results, the ZBD in ClpX clearly plays a major role in substrate binding and cofactor recognition, as well as in substrate translocation into the ClpP chamber.

Advisor: Houry, Walid A.
First-order Decision-theoretic Planning in Structured Relational Environments

We consider the general framework of first-order decision-theoretic planning in structured relational environments. Most traditional solution approaches to these planning problems ground the relational specification w.r.t. a specific domain instantiation and apply a solution approach directly to the resulting ground Markov decision process (MDP). Unfortunately, the space and time complexity of these solution algorithms scale linearly with the domain size in the best case and exponentially in the worst case. An alternate approach to grounding a relational planning problem is to lift it to a first-order MDP (FOMDP) specification. This FOMDP can then be solved directly, resulting in a domain-independent solution whose space and time complexity either do not scale with domain size or can scale sublinearly in the domain size. However, such generality does not come without its own set of challenges and the first purpose of this thesis is to explore exact and approximate solution techniques for practically solving FOMDPs. The second purpose of this thesis is to extend the FOMDP specification to succinctly capture factored actions and additive rewards while extending the exact and approximate solution techniques to directly exploit this structure. In addition, we provide a proof of correctness of the first-order symbolic dynamic programming approach w.r.t. its well-studied ground MDP counterpart.

Advisor: Boutilier, Craig
Solving Quantified Boolean Formulas

Abstract Solving Quantified Boolean Formulas Horst Samulowitz Doctor of Philosophy Graduate Department of Computer Science University of Toronto 2008 Many real-world problems do not have a simple algorithmic solution and casting these problems as search problems is often not only the simplest way of casting them, but also the most efficient way of solving them. In this thesis we will present several techniques to advance search-based algorithms in the context of solving quantified boolean formulas (QBF). QBF enables complex realworld problems including planning, two-player games and verification to be captured in a compact and quite natural fashion. We will discuss techniques ranging from straight forward pre-processing methods utilizing strong rules of inference to more sophisticated online approaches such as dynamic partitioning. Furthermore, we will show that all of the presented techniques achieve an essential improvement of the search process when solving QBF. At the same time the displayed empirical results also reveal the orthogonality of the different techniques with respect to performance. Generally speaking each approach performs well on a particular subset of benchmarks, but performs poorly on others. Consequently, an adaptive employment of the available techniques that maximizes the performance would result in further improvements. We will demonstrate that such an adaptive approach can pay off in practice, by presenting the results of using machine learning methods to dynamically select the best variable ordering heuristics during search.

Keywords: Artificial Intelligence
Satisfiability
Search
Quantified Boolean Formulas
Advisor: Bacchus, Fahiem