VictorJuiz/thesis huggingface dataset:
Using Reporter Synthetic Genetic Array (R-SGA) analysis to explore cell cycle-regulated transcription in budding yeast

The temporal control of transcription is likely a universal feature of cell cycles with clear transcriptional programs in yeast, bacteria and metazoans. A number of transcription factors and other regulators that control cell cycle transcription have been identified, yet our overall understanding of the regulatory network behind cell cycle-dependent gene expression remains incomplete. To systematically identify new regulators of cell cycle transcription, I took advantage of a system called Reporter Synthetic Genetic Array (R-SGA) analysis, which exploits fluorescent reporter genes and automated yeast genetics to discover genetic perturbations that influence the activity of cell cycle-regulated promoters. The R-SGA system has been productively used to identify gene deletions that affect histone gene expression. I adapted the system for use with arrays of yeast strains that enable systematic scrutiny of the effects of gene overexpression and loss-of-function lesions in essential genes on cell cycle-dependent promoters. I used the optimized R-SGA protocol to generate a unique data set describing genetic alterations that influence expression of 27 cell cycle-dependent promoters that broadly represent different cell cycle stages. I also developed an orthogonal flow cytometry assay to complement the plate-based R-SGA method to measure reporter-gene activity on a single cell level. I optimized a data normalization pipeline to analyze 270,000 genetic tests to produce a final dataset comprised of 1000 deletion or overexpression mutations that influence the activity of one or more cell cycle-regulated promoters. The resultant dataset is rich in biological information, with unique insights resulting from screening overexpression versus loss-of-function alleles. I reasoned that the genes encoding proteins that directly influence promoter activity may show opposite responses to gene deletion or overexpression. Indeed, the roster of genes that influence cell cycle-dependent promoters when both overexpressed and deleted includes known direct regulators as well as uncharacterized genes. I explored one such gene, SRL2, and uncovered its function as a regulator of G1 transcription especially under stress conditions.

Keywords: budding yeast
cell cycle
histone genes
Reporter-SGA
SRL2
transcription
Advisor: Andrews, Brenda J
Crystallization of Synthetic Blast Furnace Slags Pertaining to Heat Recovery

Heat recovery from blast furnace slags is often contradicted by another requirement, to generate amorphous slag for its use in cement production. As both the rate and extent of heat recovery and slag structure are determined by its cooling rate, a relation between the crystallization kinetics and the cooling conditions is highly desired. In this study, CaO-SiO2-Al2O3-MgO (CSAM) slags with different basicities were studied by Single Hot Thermocouple Technique (SHTT) during isothermal treatment and non-isothermal cooling. Their time-temperature-transformation (TTT) and continuous-cooling-transformation (CCT) diagrams were plotted and compared with each other. Furthermore, kinetic parameters such as the Avrami exponent (n), rate coefficient (K) and effective activation energy of crystallization (E_A) were found by analysis of data obtained from in-situ observation of glassy to crystalline transformation and image analysis. Also, the dependence of nucleation and growth rates of crystalline phases were quantified as a function of time, temperature, and slag basicity. Together with the observations of crystallization front, they facilitated establishing the dominant mechanisms of crystallization. In addition to the experimental work, a mathematical model was developed and validated that predicts the amount of crystallization during cooling. A second mathematical model that calculates temperature history of slag during its cooling was coupled with the above model, to allow studying the effect of parameters such as the slag/air ratio and granule size on the heat recovery and glass content of slag.

Keywords: Blast Furnace Slag
Crystallization
Dry Granulation
Heat Recovery
Single Hot Thermocouple Technique (SHTT)
Slag Cement
Advisor: Barati, Mansoor
Dramatic Encounters: Drama Pedagogy and Conflict in Social Justice Teaching

This study examines social justice teaching through drama and conflict pedagogies, and diverse students’ responses to these pedagogies, infused in academic curriculum practice in three publicly funded urban classrooms (grades 4-8). Qualitative and arts-based methodologies included teacher interviews, participant observation, and students’ improvised drama workshops facilitated by the researcher. The three participating teachers, working in demographically different (privileged and marginalized) contexts, conceptualized and taught social justice education through drama pedagogies that embraced conflict as a learning opportunity. Each emphasized a somewhat different approach: critical care (learning about Others and interpersonal relationships); critical shit disturbing (questioning to elicit conflict and tools for developing agency); cautious risk taking (eliciting multiple understandings of broad social issues, acknowledging uncertainty). These three teachers addressed justice primarily in affirmative ways, and sometimes set the stage for potentially transformative justice education (Fraser, 2005). Students from each classroom had contrasting interpretations of social justice, and responded to their teachers’ pedagogies with varied, sometimes contradicting, forms of engagement, including humour and silence. The findings reveal a set of tensions within the pedagogical “dramatic encounter”. 1, Teachers’ perceptions of students’ differences were key to how they taught, and identities also influenced students’ responses to social justice and drama pedagogies. Students with more personal experience with oppression tended to make improvisational drama choices that addressed broader social structural issues, while others tended to remain distant from oppression by dramatizing issues only as generic interpersonal conflicts. 2, Social justice drama pedagogies surfaced danger and potential: conflict in these pedagogies could be (but was not always) generative and agonistic (constructive rather than antagonistic). 3, Carefully designed pedagogies that allocated time to dramatic processes created opportunities for students’ expressed understandings to develop complexity. This study provides complex examples of social justice education through drama and conflict embedded in varied subject areas that were demonstrably feasible in three contrasting public classrooms with young students. This study shows the challenges of seeking one right way to teach conflict, drama, and social justice in all contexts, and recognizes ways students participate in the refashioning of social justice for their own lives.

Keywords: Conflict
Drama education
Elementary students
Elementary teaching
Social justice
Social studies education
Advisor: Bickmore, Kathy
Managing Design-Time Uncertainty in Software Models

The concern for handling uncertainty in software pervades contemporary software engineering. A particular form of uncertainty is that which can exist at multiple stages of the development process, where developers are uncertain about the content of their artifacts. However, existing tools and methodologies do not support working in the presence of design-time uncertainty, i.e., uncertainty that developers have about the content of their artifacts in various stages of the development process, therefore having to mentally keep track of multitude of possible alternative designs. Because of this uncertainty, developers are forced to either refrain from using their tools until uncertainty is resolved, or to make provisional decisions and attempt to keep track of them in case they prove premature and need to be undone. These options lead to either under-utilization of resources or potentially costly re-engineering. This thesis presents a way to avoid these pitfalls by managing uncertainty in a systematic way. We propose to to work in the presence of uncertainty and to only resolve it when enough information is available. Development can therefore continue while avoiding premature design commitments. In a pilot user study we found that, when asked to articulate design-time uncertainty in a free-form modelling scenario, people tend to explicate it within the software artifact itself, staying close to the existing notation. This lead us to adopt "partial models", a formalism for representing sets of possible design alternatives while staying faithful to the underlying language. This way, the problem of managing uncertainty in software artifacts is turned into a problem of doing management of software artifacts that contain uncertainty. To manage partial models, we have thus leveraged several software engineering sub-disciplines to develop techniques for: (a) articulating uncertainty, (b) checking and enforcing properties, as well as generating appropriate user feedback, (c) applying transformations, and (d) systematically making decisions, as new information becomes available. The resulting partial model management framework utilizes novel abstraction and automation approaches and enables a principled and systematic approach to managing design-time uncertainty in the software development process.

Keywords: Model Transformation
Partial Models
Software Engineering
Software Modelling
Software Processes
Software Verification
Advisor: Chechik, Marsha
English Word Reading Profiles of Chinese Dyslexic Students

This study explored the English word reading profiles of Chinese dyslexic and typically developing children in Hong Kong. A mixed methods design was employed to compare the English word reading abilities, phonological processing, word reading strategies, home environment, and goal orientations of the two groups. Four students with Chinese dyslexia and five typically developing students enrolled in grades four to six in Hong Kong elementary schools completed a battery of standardized tests measuring phonological awareness, phonological memory, rapid naming, reading fluency as well as word and nonword reading. They also completed a demographic questionnaire and a goal orientation questionnaire. Finally, they participated in a read-aloud activity and an interview regarding their experiences of learning English. Mann-Whitney tests showed that the dyslexic children performed significantly lower than the typically developing children on phonological memory, rapid letter naming, some aspects of phonological awareness, reading fluency and word reading. Integrative text and miscue analyses also showed that typically developing children generally made use of a wider variety of strategies in reading more effectively as compared to the dyslexic children. These findings largely corroborate those found in research with monolingual English children. This suggests that the English word reading difficulties Chinese students encounter are mostly attributable to the presence of dyslexia and not to difficulties with the orthography of the English language

Keywords: Chinese dyslexia
experiences in learning English
miscue analysis
phonological processing
word reading profiles
word reading strategies
Advisor: Chen-Bumgardner, Becky (Xi)
Natural Agency: An Ecological Approach

Agency, the capacity to act for a goal or purpose guided by norms, is central to our understanding of the capacities and activities of organisms including human beings. However, its distinctive purposive and normative character has proven difficult to integrate with the scientific understanding of organisms as natural physical entities. The challenge is to show both that agency has a place in the natural causal order of the world as described by natural science (naturalism), and that its distinctive purposive and normative character plays an indispensable role in our understanding of natural phenomena (teleology). The standard approaches, however, either locate agency in the natural causal order of the world but fail to vindicate its distinctive purposive and normative character, or vice versa. My goal is to avoid this dichotomy and instead offer a complete unifying account of natural agency. In the first part of the thesis I address the methodology of naturalism. First, I argue that the standard approaches are committed to an unnecessarily stringent set of assumptions about what naturalism requires. And second, I propose an alternative methodological strategy based on scientific work in complex systems dynamics. In the second part I use this strategy to articulate a novel account of natural agency, The Ecological Theory of Agency. This account is based on recent empirical and philosophical work in evolutionary developmental biology on the organism-environment relation (Walsh 2013). An agent, I propose, is an ecologically embedded purposive system. That is, a system with the gross behavioral capacity to bias its repertoire in response to what its conditions afford for attaining its goals. Then I show how the solution that this account of agency provides generalizes to two other instances of the dichotomy. The first is the problem of bacterial cognition. I show how the ecological approach allows us to navigate a middle way between thinking of unicellular organisms as either mere automata or full-blown cognitive agents. The second is the problem the role that reasons play in the explanation of action. I show that the ecological approach avoids thinking of reasons as either exclusively causes or exclusively norms.

Keywords: Affordances
Agency
Naturalism
Normativity
Repertoire
Teleology
Advisor: Walsh, Denis M
Phenotypic Impact of Genetic Risk Pathways for Alzheimer's Disease

The contribution of genetic variation to the risk for late-onset Alzheimer’s disease is well-accepted; however, the roles of specific mutations within established risk genes are not clear. Comprehensive datasets with informative in vivo and postmortem biomarkers now offer the opportunity to understand when, where, and how mutations within these genes individually exert their effects on the brain. Moreover, it is known that many of these genes interact at the pathway level, and therefore genetic effects should also be considered in context using gene-gene interaction approaches. I hypothesized that common functional variants modifying established Alzheimer’s risk pathways would demonstrate a) independent effects and b) synergistic effects on human brain structure and other Alzheimer’s biomarkers. First, the Apolipoprotein E (APOE) gene ε4 mutation was found to be associated with white matter integrity in an age-dependent manner. Second, mutations within the sortilin-like receptor (SORL1) gene were associated with differences in white matter integrity, SORL1 gene mRNA expression, and amyloid neuropathology that suggested an early genetic risk mechanism beginning as early as childhood. Third, a translocator protein (TSPO) gene variant known to alter TSPO binding characteristics was found to have no direct effects on inflammatory and cerebrovascular brain changes in over 2 300 elderly subjects. Finally, based on evidence from recent human stem cell experiments, RNA sequencing was used to identify a novel interaction of gene variants across the SORL1 gene with the brain derived neurotrophic factor (BDNF) Val66Met polymorphism regulating isoform-specific SORL1 expression related to amyloid pathology and brain structural alterations. Altogether, these experiments demonstrate that some genetic modifiers of AD risk pathways are linked either directly via biochemical function or indirectly via the convergence of pathways they influence. These studies have begun to parse the immense heterogeneity of the Alzheimer’s disease diagnosis as well as uncover distinct genetically-defined molecular subtypes of at-risk individuals who should be targeted in future therapeutic trials. Novel interventions designed to engage specific neural circuits or molecular pathways would be of most benefit to the molecular subtypes in which they are most greatly altered.

Keywords: Alzheimer's Disease
Imaging-Genetics
MRI
Multidisciplinary
Neuroimaging
Neuropathology
Advisor: Voineskos, Aristotle N
Kennedy, James L
Development of Suspension Plasma Sprayed Lanthanum Perovskite Ceramic Layers for Clean Energy Technologies

This thesis is devoted to developing the suspension plasma spraying process for fabricating ceramic layers applicable to green energy technologies, i.e., solid oxide fuel cell cathodes and oxygen separation membranes. The materials of interest for this study include the mixed ionic and electronic conducting perovskite lanthanum strontium cobalt ferrite (LSCF), its composite with yttria-stabilized zirconia (YSZ), and the excellent electronically, but less ionically, conductive perovskite lanthanum nickel ferrite (LNF). The objective of this thesis is to investigate the processing-property relationships between the plasma spray parameters and resulting properties of coatings fabricated with them, and to use the resulting understanding to fabricate dense coatings for oxygen separation membranes and porous coatings for fuel cell cathodes on stainless steel substrates. It was observed that fairly dense LSCF coatings can be fabricated by suspension plasma spraying, but the gas-tightness was dictated by the coating thickness required to bridge the surface pores on the supporting metal substrate. Higher porosity of the cathode layers was obtained by adding carbon black pore former into the feedstock suspension, and single-phase LSCF cathodes made in this way exhibited excellent symmetrical fuel cell performance with a polarization resistance of 0.062 立cm2 at 744oC. Fabricating an LSCF/YSZ composite by plasma spray processing was more difficult, because the plasma power must be sufficient to melt the YSZ phase without decomposing the LSCF phase. The composite cathodes fabricated had lower performances than those of the single-phase cathodes. The suspension plasma sprayed LNF cathodes had higher polarization resistances and lower durability than those of suspension plasma sprayed LSCF cathodes due to severe material decomposition. Therefore, single-phase LSCF cathodes were chosen for short-term and medium-term durability testing in full fuel cells. It was demonstrated that suspension plasma sprayed single-phase LSCF cathodes with the fine microstructures, and thus, large surface area for reactions, performed comparably to more-expensive dry powder plasma sprayed LSCF/SDC composite cathodes in a complete fuel cell, even though the latter cathodes have a higher overall ionic conductivity.

Keywords: Cathode
LNF
LSCF
Oxygen Separation Membrane
Solid Oxide Fuel Cell
Suspension Plasma Spraying
Advisor: Kesler, Olivera
Design of Algal Film Photobioreactors for Algal Biomass Production

Microalgae has been identified as a potential feedstock for both biofuels and biochemicals but dewatering algae limits the economic viability. By growing algae as a biofilm, the cost of dewatering can be reduced. Current design of algal film photobioreactors is limited to algal turf scrubbers and rotating algal biofilm systems. There is opportunity to explore new designs based on growing algal biofilms on a light emitting waveguide. The growth of algal films on transparent surfaces with polar surface energy ranging from 7-11.3 mJ/m2 was tested in a Parallel Plate Airlift Reactor. Overall algal biofilm productivity is correlated to the colonization time of the biofilm, with algal films grown on cellulose acetate having the highest productivity of 2.1 g/m2 day. When colonization time was accounted for, the approximate 2 g/m2 day algal biofilm productivity was independent of material. Colonization time was correlated to the polar surface energy and not the water-material contact angle. Lipid content of algal biofilms ranged from 6-8 w%/w and were independent of the material it was grown on. To demonstrate the feasibility of growing algal biofilms on light emitting waveguides, five different waveguide designs were fabricated and the light emission from all the surfaces was measured. Light intensity distribution on the waveguides could be adjusted by surface modification. Algal biofilms grown on these waveguides had overall non-linear growth kinetics and the highest surface area productivity was 2.9 g/m2 day. The productivity was dependent on the light intensity (incident photon flux from 1600-12600 Îźmol/m2 sec) and CO2 concentration (0.04-3% partial pressure), but saturation effects were observed. The interaction effects between light intensity and CO2 concentration on algal biofilm productivity was non-linear. A fundamental model was developed to describe light and inorganic carbon dependent algal biofilm growth. Incident light direction, intensity, and inorganic carbon concertation was varied. A complimentary model based on a partial differential equation was also developed which describes light limited growth. Predicted growth kinetics were sigmoidal in shape and showed agreement with experimental data. Effects such as light-dark cycles were not fully captured by the model, which suggests there is room for improvement.

Keywords: Algae
Algal Biofilm
Bioreactor
Photobioreactor
Advisor: Allen, D. Grant
Aitchison, J. Stewart
Rescaled Directed Random Polymer in Random Environment in Dimension 1+2

Directed random polymer in random environment is a statistical physics model. Heuristically, it concerns a long, directed chain of molecules evolving in some random background, and one of the questions one asks is how is long term behaviour of the polymer affected by the strength of the noise, which in the model is controlled by a parameter β called inverse temperature. In this thesis, we will let β depend on the length of the polymer and consider the model in time-space dimension 1+2. Also, we will work with continuous time and space, and Gaussian random environment that is white noise in time.

Keywords: Brownian Motion
Critical Scaling
Gaussian Correlation Inequality
Large Deviation
Random Polymer
Two Dimensional Local Time
Advisor: Quastel, Jeremy
Virus-mediated Delivery of the Fmr1 Gene as a Tool for the Treatment of Fragile X Syndrome

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a trinucleotide repeat expansion in the FMR1 gene that codes for fragile X mental retardation protein (FMRP). The goal of the present study was to determine whether restoring FMRP expression in the brains of the Fmr1 knockout (KO) mouse model of FXS could correct the disorder. Initially, we investigated major factors affecting tropism, expression level, and cell-type specificity of adeno- associated viral vectors (AAV), including encapsidation of different AAV serotypes, promoter selection, and the timing of vector administration, using intra-cerebroventricular injections of AAV vectors expressing enhanced green fluorescent protein. Our results favored the use of AAV serotype 9 (AAV9) vectors containing the neuron-selective synapsin-1 promoter, injected into the lateral ventricles of neonatal mice. To determine if FMRP expression in the central nervous system could reverse phenotypic deficits in the Fmr1 KO mouse model of FXS, we used a single-stranded AAV9 that contained a major isoform of FMRP. The vector was delivered to the brain via a single bilateral intra-cerebroventricular injection into neonatal Fmr1 KO mice on postnatal day 5 (in the first phase of the study) or 0-1 (in the second phase). Transgene expression and behavioral assessments were conducted either 22-26 or 50-56 days post-injection. Western blotting and immunocytochemical analyses of AAV-FMRP-injected mice revealed neuron-specific FMRP expression in the striatum, hippocampus, retrosplenial cortex, and cingulate cortex. AAV-FMRP injections reversed the pathologically elevated repetitive behavior and the deficit in social dominance behavior seen in Fmr1 KO mice in phase 1, as well as the elevated startle response and lower anxiety in phase 2. These results provide the first proof-of-principle that gene therapy can correct specific behavioral abnormalities in the mouse model of FXS.

Advisor: Hampson, David R