VictorJuiz/thesis huggingface dataset:
The Role of the Atypical Cadherin Fat4 during Early Mouse Kidney Induction and Mesenchymal to Epithelial Transition

Mammalian kidney development is a tightly regulated process that requires proper signaling among three different cellular compartments: the ureteric bud (UB; epithelial), the condensing mesenchyme (CM) and the stroma. Improper signaling between these three cell lineages can result in renal hypoplasia and/or dysplasia. Fat4 is an atypical cadherin involved in planar cell polarity (PCP), growth and cell adhesion. It has been proposed that Fat4 might work with another atypical cadherin Dachsous1 (Dchs1) and the Golgi-localized kinase Four-jointed1 (Fjx1). My thesis examined Fat4 and novel genetic interactions with Fat4 during two stages of mouse kidney development: nephron progenitor renewal and early kidney induction. I determined that Fat4-/- single mutants have an expanded renal progenitor pool (i.e. larger CM aggregates) and found that this phenotype is independent of core PCP and Hippo signaling. Loss of Dchs1 also resulted in expansion of the CM. Tissue-specific deletions show that Fat4 acts non-autonomously in the renal stroma to regulate the nephron progenitor pool. Gene expression analyses demonstrated that BMP, Notch and FGF signaling are altered in Fat4 mutants. I also found that Fat4-/-;Fjx1-/- double mutants exhibit duplex kidneys. Since increased GDNF-RET signaling also leads to duplex kidneys, I reduced GDNF signaling by examining GDNF+/-;Fat4-/-;Fjx1-/- triple mutants. Importantly, these mice did not exhibit duplex kidneys, suggesting that Fat4 and Fjx1 suppress excessive levels of GDNF-RET signaling. Overall, my thesis supports a model whereby 1) FAT4 in the stroma binds to DCHS1 in the CM to restrict renal progenitor self-renewal and, 2) Fat4 and Fjx1 restrict GDNF-RET signaling during kidney induction and subsequent branching.

Keywords: cadherins
duplex kidneys
Fat4
kidney development
Mouse
nephron progenitors
Advisor: McNeill, Helen
Novel Boron Subphthalocyanines for Organic Electronic Devices

Boron subphthalocyanines (BsubPcs) are a class of organic semiconductor materials that have been identified as having desirable properties for use in photovoltaic devices due to their strong light absorbance and the flexibility to develop tunable chemical derivatives. In particular, a lack of variety in available electron acceptors is an area where BsubPc derivatives can be readily substituted into existing photovoltaic device architectures. There are, however, no metrics to facilitate the rapid screening of different BsubPc derivatives. In this thesis, admittance spectroscopy is used to measure charge carrier mobility of these BsubPc derivatives, and photovoltaic cells are fabricated to evaluate these derivatives’ performance in devices. We find that the measured electron carrier mobilities in thin films of BsubPc correlate with the single crystal structural parameters determined by X-ray diffraction. We also find that for BsubPcs, electron mobility measured by admittance spectroscopy is insufficient to predict photovoltaic performance when BsubPcs are used as an electron accepting layer in a device. BsubPc derivatives, however, are discovered as a new class of versatile molecules that can be designed and synthesized for use in photovoltaic devices to harvest singlet fission derived triplet excitons and consequently boost photovoltaic device photocurrent. This thesis also reports vacuum system design and construction to address experimental challenges arising from dealing with low solubility, high molar mass materials and limited amounts of high purity material.

Keywords: charge carrier
mobility
photovoltaic
singlet fission
triplet
Advisor: Bender, Timothy P.
Lu, Zheng-Hong
A Struggle for Hearts and Minds: Statebuilding and Origins of Political Legitimacy in Post-2001 Afghanistan

This thesis tackles a central puzzle of externally-assisted statebuilding: why international efforts to rebuild states with more capacity do not necessarily result in more internal legitimacy. It examines the dynamics of state legitimacy in Afghanistan since the fall of the Taliban by tracing dominant understandings of political legitimacy that came to characterize the international statebuilding project; (de)legitimizing practices of the Afghan state and external actors; and in turn, citizen evaluations of state institutions. Unlike scholars who interpret legitimacy as automatically following from particular kinds of institutions (namely those associated with liberal democracy), this thesis suggests that legitimacy is best understood as resulting from complex interactions between state, society and – in the context of externally-assisted statebuilding – international actors. The study finds that despite initial optimism and the existence of a state that provides more to its citizens than has historically been the norm, many Afghans have grown critical of state institutions. This shift in perceptions owes in large part to the conflicted approach to governance taken by the international statebuilding project. I argue that international actors first positioned good governance as a core criterion against which to judge the legitimacy of the Afghan state, which represented a departure from traditional understandings of political legitimacy in the country. Despite this emphasis, external actors then contributed to a dysfunctional governance environment characterized by a polarization of power, an uneven distribution of resources, and high levels of external intrusiveness in local politics, especially in Afghanistan’s insecure southern provinces. Aligning with these arguments, this dissertation finds that local attitudes towards international actors are instrumental in determining Afghans’ perceptions of state legitimacy, especially in the South where external actors were more invasive in shaping the statebuilding project. Secondly, it finds that key governance indicators – namely the state’s perceived inclusiveness, responsiveness and fairness – are critical drivers of legitimacy, particularly in the South where the gap was especially great between the rhetoric of good governance and governance failings on the ground. These findings help to position political legitimacy at the center of conversations about statebuilding efforts, and contribute to a richer understanding of state legitimation during international intervention.

Keywords: Afghanistan
Political legitimacy
Political trust
Statebuilding
Advisor: Fletcher, Joseph F.
Topological Aspects of Real-valued Logic

We study interactions between general topology and the model theory of real-valued logic. This thesis includes both applications of topological ideas to obtain results in pure model theory, and a model-theoretic approach to the study of compacta via their rings of continuous functions viewed as metric structures. We introduce an infinitary real-valued extension of first-order continuous logic for metric structures which is analogous to the discrete logic Lω(1),ω, and use topological methods to develop the model theory of this new logic. Our logic differs from previous infinitary logics for metric structures in that we allow the creation of formulas inf nϕn supnϕn for all countable sequences (ϕn)n <ω of formulas. Our more general context allows us to axiomatize several important classes of structures from functional analysis which are not captured by previous logics for metric structures. We give a topological proof of an omitting types theorem for this logic, which gives a common generalization of the omitting types theorems of Henson and Keisler. Consequently, we obtain a strengthening of a result of Ben Yaacov and Iovino concerning separable quotients of Banach spaces. We show that continuous functions on separable metric structures are definable in our Lω(1),ω if and only if they are automorphism invariant. The second part of this thesis develops the model theory of the C*-algebras C(X), for X a compact Hausdorff space. We describe all complete theories of these algebras for X a compact 0 -dimensional space. We show that the complete theories of C(X) (for X of any dimension) having quantifier elimination are exactly the theories of C, C2, and C(2N) , and that if the theory of C(X) is model complete and X is connected then X is co-elementarily equivalent to the pseudoarc. We use model-theoretic forcing to answer a question of P. Bankston by showing that the pseudoarc is a co-existentially closed continuum.

Keywords: C*-algebra
Continuous logic
Infinitary logic
Model theory
Topology
Advisor: Tall, Franklin
Iovino, José
Advancing Theory in Healthcare Simulation Instructional Design: The Effect of Task Complexity on Novice Learning and Cognitive Load

Dramatic changes to healthcare systems globally have led to increased use of simulation as a pedagogical tool in health professions education. An impressive evidence base has accrued in support of simulation-based education and training, leaving little doubt that ‘it works’. As a result, scholarship in the field is shifting toward clarifying the features of simulation instructional design that optimize learning outcomes. Many scholars advocate for the use of established instructional frameworks to advance this agenda. In this dissertation, the author employed Cognitive Load Theory (CLT) and related instructional frameworks to investigate the relationship between task complexity, cognitive load (CL), and learning among novices engaged in simulation-based procedural skills training. Phase one of this research program established the sensitivity of two CL measures (subjective ratings of mental effort and secondary task performance) to predicted differences in load related to learners’ proficiency with a procedural skill and simulation training task complexity. As a result, these measures may be used to track changes in CL during simulation training and distinguish between the CL imposed by different instructional designs. Phase two operationalized Elaboration Theory (ET) to identify the task-conditions that impact training complexity of a prototypical procedural skill (lumbar puncture). The results of this phase demonstrate the methodological and theoretical advantages of combining a structured instructional design framework with expert consensus (via the Delphi technique) when developing healthcare simulation curricula. The final phase examined the competing effects of task complexity and context similarity on novices’ skills transfer. The results demonstrate that higher task complexity increases load during training, which may impede initial learning and subsequent transfer of skills ‘peripheral’ to the task (e.g. sterility). However, the findings also suggest that other variables (i.e. context or information processing specificity and learners strategies to manage load) may have important effects on these learning outcomes. At a broader level, the systematic, multi-phased approach employed in this dissertation provides a framework to guide future research in simulation instructional design. Furthermore, the application of CLT in this work exposes strengths and shortcomings in the theory that educators and researchers should be aware of, and highlights avenues for future inquiry.

Keywords: Cognitive Load Theory
Fidelity
Healthcare simulation
Health professions education
Instructional design
Procedural and surgical skills
Advisor: Dubrowski, Adam
A Geoarchaeological Investigation of Storage and Surplus at Tel Tsaf, Israel

The Chalcolithic period of the southern Levant spans from c. 5800 - 3600 cal BC. Traditional hallmarks of this period include caches of copper items, non-domestic shrine sites and large off site cemeteries or burial caves. However, these features date to the later portion of the period (Late Chalcolithic) and date to c. 4400 cal BC onwards. The focus of this dissertation is on the Middle Chalcolithic period (c. 5040 – 4440 cal BC), specifically in relation to storage and access to resources at the village of Tel Tsaf, Israel. Excavations at Tel Tsaf uncovered evidence of at least four walled courtyard complexes spanning two Chalcolithic phases. Each courtyard contained either rectangular broadroom houses or circular buildings, with no evidence of both structural forms in the same courtyard. Each courtyard also contained multiple large, mudbrick-lined circular silos. The research goals of this work address the implications of these varied architectural forms and the possible identification of surplus of both floral and faunal goods. Microscopic sediment analysis was used to investigate these questions, and the results are discussed in relation to the big picture debates of the Chalcolithic period. Micromorphology and bulk sediment samples were taken from Building Complexes I, II and IV during the 2006 and 2007 field seasons. Results demonstrate that domestic activities centred in the broadroom house and courtyard of Building Complex I, and animal penning activity was restricted to the circular buildings in Building Complex II. This distribution, combined with the numerous large silos, indicate there may have been some economic specialization at Tel Tsaf. The relationship among storage, surplus and wealth is explored and put in context of public and private access to resources and potential feasting at the site. It is established that the evidence is not significant enough to classify Tel Tsaf or the Middle Chalcolithic societies as chiefdoms. The evidence of likely surplus and potential private ownership of animals without evidence of a central distribution system or regional hierarchy further differentiates Tel Tsaf from large Late Chalcolithic villages. However, the evidence from Tel Tsaf demonstrates that it is distinct from the Early and Late Chalcolithic sites, demonstrating some similarity to both periods, as well as some evidence unique to the Middle Chalcolithic.

Keywords: Chalcolithic
geoarchaeology
micromorphology
Surplus of goods
Advisor: Banning, Edward
Maher, Lisa
Improv Remix: Video Manipulation Using Whole-body Interaction To Extend Improvised Theatre

This work represents a technical implementation of features seen in modern theatrical improvisation: re-use of previous concepts and moments in performance via recontextualization, coordinated by gestures between the performers on stage. We present a system for manipulating the video content of a stage show, and re-projecting previous moments on the stage. As part of this thesis, we have explored the generic research problems of live video editing and separating for-system interaction (foreground activity) from noisy gesticulation (background activity). We have workshopped and designed iterations of our system extensively with experienced theatrical improvisation performers. We have exhibited this work in a public showcase, and have observed the impact on interacting with a system, while performance is the primary activity, on both performance and audience members. We provide several use cases discovered during performance, and reflect on thinking of theatrical improv performers as a special group of users.

Keywords: improvisation
interaction techniques
remix
video editing
whole-body interaction
Advisor: Balakrishnan, Ravin
Predicting Individual-level Probabilities of Dementia and Diabetes using Health Services Administrative Data

Health services administrative data (HSAD) provide a timely and readily available population-based data source for health research and planning. To perform disease-specific analyses, individuals with the disease must first be identified in the administrative data. In this validation study, a data modeling method (logistic regression) and two algorithmic modeling methods (random forests and gradient boosted machines) were compared in predicting individual-level probabilities of diabetes and dementia using HSAD. Prevalence for both diseases was calculated to demonstrate a population-level application and A1C testing rates were calculated to demonstrate an individual-level application. Diabetes prevalence and A1C testing rates were compared with the classification-based methods currently used for the Ontario Diabetes Database (ODD). The reference standard data were chart re-abstraction data for a sample of Toronto-areas physician for diabetes and the Ontario sample of the Canadian Study of Health and Aging for dementia. The three-year random forest models were the best-performing models for both diabetes (Nagelkerke’s R2=0.82, C statistic=0.98 and calibration slope=1.02) and dementia (Nagelkere’s R2=0.58, C statistic=0.92 and calibration slope=1.00). Based on the random forest probabilities, the prevalence of dementia in Ontario in 2008/09 was 8.5 percent for females and 5.7 percent for males. The prevalence of diabetes was 5.4 percent for females and 6.5 percent for males. A1C testing rates varied from 38 to 61 percent depending on the probability cutoff used. The probability-based diabetes prevalence was lower than the ODD-based rates and the A1C testing rates were higher than the ODD-rates. Although the random forest models are more complex than the pooling algorithms currently used for the ODD, they offer researchers the flexibility to construct cohorts with sensitivities and specificities specific to each purpose. Algorithmic modeling methods are well suited to research using health services administrative data and should be pursued as an alternative to data modeling methods.

Keywords: administrative data
health services research
machine learning
performance measurement
probabilities
surveillance
Advisor: Anderson, Geoffrey
Fishing for a Zebrafish model of Fetal Alcohol Spectrum Disorder: The Behavioural Characterization and a Biological Exploration of the Effects of Embryonic Alcohol Exposure on Zebrafish

Fetal alcohol spectrum disorder (FASD) is the leading cause of birth defects in the Western world. Individuals with FASD may suffer from physical deformities and /or behavioural and cognitive impairments that are life long, severely reducing their quality of life while placing a financial burden on society. In order to address the aforementioned issues it is necessary to unravel the mechanisms underlying FASD. Animal models can aid in elucidating the mechanisms involved in FASD. The zebrafish possess a number of behavioural and biological characteristics making them a suitable animal model for FASD research. In the past this species has been used to explore the effects of embryonic alcohol exposure (EAE) on physical features. While a few studies have begun to investigate the impact EAE has on social behaviour, these studies utilized a live group of zebrafish (shoal) to assay the behaviour. Previously, I demonstrated that a computerized shoal could be used to study the behavioural deficits associated with EAE; specifically, I found a dose-dependent decrease in social behaviour in exposed fish. The research presented within this thesis represents an expansion of my previous research. Beginning by optimizing the parameters of the computerized stimulus, I was able to demonstrate that the size and the number of fish within the animated shoal effects the social behaviour of experimental fish. Using the optimized social paradigm, I showed that the deficits in social behaviour caused by EAE are stage-specific and that these social impairments do not subside with age. I used high-pressure liquid chromatography to determine whether the changes in social behaviour caused by EAE were accompanied by changes to the dopamine system, finding that EAE did impair the dopaminergic system. I was also successful at developing a new apparatus that is capable of assaying many behaviours in zebrafish, including associative learning and memory.

Keywords: Dopamine
Fetal alcohol spectrum disorder
High throughput
Impaired social behaviour
Learning and memory
Zebrafish
Advisor: Gerlai, Robert T
Applications of Fourier coefficients of modular forms

Let f be a modular form of even weight k and level N which is a normalized eigen-form for the Hecke operators, and write [special characters omitted] for its Fourier expansion at i∞. We assume the Fourier coefficients {af(n)}(∞/n=1 are rational integers. A notable example of such a form is Ramanujan's cusp form Δ of weight 12 and level 1. In this case, the Fourier coefficients are given by the famous Ramanujan tau function: [special characters omitted] In this thesis, we study applications of the Fourier coefficients τ( n), and more generally, af( n). First, we present a factoring algorithm that uses an oracle that outputs af(n) . We show that the algorithm runs in polynomial time for squarefree integers on average, and quasi-polynomial time for non-squarefree integers on average. We note that current factoring algorithms have sub-exponential runtimes. More importantly, when combined with Edixhoven's (conditional) polynomial time algorithm for computing af(p), we get an equivalence between factoring and computing af(n) . Secondly, we present an algorithm that uses an oracle that outputs af(n) for testing the squarefree-ness of an integer. This algorithm exploits the greatest common divisor of sequences of the form (af(pr)) r∈A where p is a prime and A ⊂ N . Thirdly, we present a primality testing algorithm that uses an oracle that outputs τ( n) and af/E}(n) where fE is a form of weight 2 corresponding to an elliptic curve. As a corollary, we use such an oracle to compute in polynomial time the value of the Möbius function in the squarefree case.

Keywords: factoring
modular forms
primality test
squarefreeness test
Advisor: Murty, Kumar
The Operating Room as a Classroom: a New Approach to Skills Assessment and Training in Surgery

Introduction: Ensuring that trainees are graduated as competent, safe surgeons who can independently perform successful operations is a social obligation. Much of surgical technical training occurs in the operating room; as a result, enhancing training in this environment needs to be a priority. In this thesis, a comprehensive training approach, based on coaching principles, is described as a means to structure the experiential learning experience of training in the operating room. Methods: Three main steps were required. Step 1: Design of an assessment methodology based on error analysis, as an adjunct to global skill assessment, to allow for comprehensive feedback. Step 2: Standardization of training content. For this, delineation of erroneous from adequate task execution was required, and causal relationships between errors and intraoperative injuries (events) needed identifying. Step 3: Design of a coaching intervention, based on observed operative performance, using established instructional approaches. Results: (1) The generic error rating tool was based on four error modes attributed to nine laparoscopic tasks. Substantial construct validity evidence was gathered through applying the tool in video analyses of routine procedures. (2) In an international Delphi consensus, definitions and examples of errors and events were obtained. Further, evidence supporting the role of errors was obtained through reviewing 66 error-event patterns identified by video analysis of routine bariatric procedures. (3) The effectiveness of the coaching intervention was demonstrated in a randomized controlled design. Coached residents (n=9) scored significantly higher on a procedure-specific skill scale (BOSATS) and made fewer technical errors than conventionally trained residents (n=9) (BOSATS median 3.90 (i.q.r. 3.68-4.30) vs. 3.60, (2.98-3.70), P=0.017; technical error 10 (7-13) vs. 18 (13-21), P=0.003). Conclusion: Designing training in a personalized fashion, following principles of coaching, can help structure experiential learning in the operating room, which leads to significantly enhanced skill acquisition in surgical training.

Keywords: Coaching
Debriefing
Error-analysis
Feedback
Postgraduate Surgical Education
Technical Skills
Advisor: Grantcharov, Teodor P