VictorJuiz/thesis huggingface dataset:
Alcohol-induced Locomotor Activity in Zebrafish is Mediated by Activation of the Dopaminergic System
Keywords: Alcohol
Dopamine
Dopamine receptor
Locomotor activity
Tyrosine hydroxylase
Zebrafish

Alcohol addiction is a major unmet medical issue with current pharmacological treatment options being limited. Alcoholâ s locomotor stimulant effect in animals is thought to parallel the euphoric effects of alcohol consumption in humans, yet the mechanisms underlying this behavioural response is not completely understood. Using zebrafish, we demonstrated a positive correlation between alcohol-induced locomotor activity and whole-brain dopamine levels. We found that zebrafish developed tolerance to alcohol's effect on locomotor and dopaminergic activity when continuously exposed to alcohol, highlighting the importance of the dopaminergic system. We correlated the alcohol-induced increase in dopamine levels with increased tyrosine hydroxylase activity and protein expression, the rate limiting enzyme in dopamine synthesis. We also found selective inhibition of phosphorylated tyrosine hydroxylase to attenuate the alcohol-induced increase in locomotor activity and abolished the increased dopamine levels. Examination of dopamine receptor activation during alcohol exposure revealed that antagonism of dopamine D1-like receptors inhibited locomotor and dopaminergic activity, although independent of alcoholâ s effect. Conversely, antagonism of dopamine D2-like receptors attenuated alcoholâ s locomotor stimulant effect suggesting an important role for this family of receptor subtypes regulating alcohol-induced locomotor activity. Finally, since alcohol is known to alter stress and anxiety in mammals, we examined the interaction between stress and alcohol in zebrafish. We found that stress and anxiety potentiated the locomotor stimulant effect of alcohol and abolished the alcohol-induced increase in dopamine. Although counterintuitive, the abolished dopaminergic response suggests stress potentiated the release and breakdown of dopamine. Overall, these studies suggest the pharmacological aspects of alcohol in mammals including humans are evolutionarily conserved in zebrafish. Given the translational relevance of our findings, future attempts to investigate novel mechanisms regulating alcohol-induced behavioural changes in zebrafish may provide key insights into alcohol addiction in humans.
Experimental and Numerical Investigations of the Behaviour of Intact Veined Andesite
Keywords: Acoustic emissions
El Teniente
Intact veined rock
Numerical modelling
Synthetic rock mass
Triaxial testing

Veined rock masses host some of the worldâ s largest mineral deposits. The fundamental behaviour of veined rock mass under load has not been fully understood. Currently there is an absence of validated engineering tools to undertake a comprehensive analysis of the behaviour of veined rock. The main objectives of this thesis are (1) to characterize the mechanical behaviour of intact veined rock in the laboratory environment in compression and (2) to develop and validate an engineering approach that captures the behaviour of intact vein rock using 3D numerical simulations. A comprehensive experimental program was instigated for intact veined andesite from the El Teniente Mine (Chile). As part of this thesis, high quality specimens were collected from the mine site and characterised using the developed Discrete Vein Network methodology. The selected rock specimens were tested under triaxial compression. The experimental program established that the veins acted as weak mechanical components in the specimens, promoting rock fracture under stress. The experimental results indicated that the stress thresholds identifying the onset of dilatancy and the transition from the stable to unstable fracturing were higher in intact veined rock than in intact rock. The observed behaviour illustrated a significant departure from intact rock where the onset of Acoustic Emissions (AE) correlates with the onset of specimen dilatancy. The experimental results from intact veined rock indicated that the onset of AE correlated with the crack damage stress. The departure from the behaviour of intact rock is attributed to the presence of veins and has significant implications on the behaviour of intact veined rock. A methodology was developed for numerical simulations of the laboratory experiments on intact veined rock using the Synthetic Rock Mass (SRM). A contribution of this thesis was the development of two sets of algorithms to capture the mechanical behaviour of intact veined rock. The first approach was based on the use of clumped Bonded Particle Models (BPM). Subsequently the Bonded Block Model (BBM) approach was further developed and implemented. This approach was shown superior in modelling and validating the intact component of veined rock. The developed numerical approaches were successful in capturing and reproducing the observed laboratory behaviour of intact veined rock. The laboratory and numerical investigations made a significant contribution in characterizing the role of veins in defining the behaviour of intact veined rock.
Regulation and Activation of PARK2-mediated Mitophagy
Keywords: Autophagy
Deubiquitinating Enzymes
Mitophagy
Parkinson Disease
Reactive Oxygen Species

An accumulation of damaged mitochondria by reactive oxygen species (ROS) can trigger apoptosis. This process has been implicated in neurodegenerative diseases such as Parkinsonâ s disease (PD). About 10% of the PD cases are caused by mutations in the PARK genes that are inheritable. The product of PARK2, Parkin, can mediate the autophagic degradation of damaged mitochondria. Autophagy is a process by which bulky cytoplasmic contents are degraded by lysosomes. PARK2 is recruited to the damaged mitochondria and ubiquitinates outer mitochondrial proteins. Ubiquitin serves as an important signal to recruit autophagy machineries to the mitochondria and deliver mitochondria to the lysosomes. Even though the major molecular events in PARK2-mediated mitophagy are revealed, how this pathway is activated and regulated remains unclear. In my thesis, I identified two deubiquitinating enzymes, ubiquitin specific protease 30 (USP30) and 35 (USP35), that can regulate PARK2-mediated mitophagy. I showed that USP30 antagonizes PARK2 activity by deubiquitinating some of the PARK2 substrates, interfering with PARK2-substrate interactions, and delaying PARK2 recruitment to the mitochondria. USP35 affects the protein and mRNA levels of mitofusins 2 as well as PARK2-substrate interactions. However, USP35 did not interfere with PARK2 recruitment. Furthermore, I described the development and characterization of a technique to activate mitophagy with a photo-sensitizer, mitochondrial-targeting KillerRed (mtKR). I showed that a sudden increase in ROS levels in the mitochondria induces mitochondrial depolarization and recruitment of PARK2. I also provided evidence that elongated mitochondria are more resistant to mtKR-induced mitophagy while fragmented mitochondria are more prone to mitophagy activation.
Understanding Social Assistance in Northern Ontario: 1997-2010
Keywords: northern ontario
social assistance
social policy
welfare reform

This study explores how the post-1997, redeveloped Ontario Works welfare system, together with the economic and social conditions in northern Ontario, influenced the administration and delivery of social assistance. In particular, this research aims to expand the limited knowledge of welfare in northern rural and non-metropolitan contexts and to increase understanding of how economic and social conditions influence the provision of the Ontario Work program. Using a constructivist grounded theory methodology, the experiences of Ontario Works program deliverers were drawn upon to foster an increased understanding of issues commonly encountered when providing social assistance to northern Ontario residents. Data were gathered over two primary periods through in-depth interviews, and follow-up interviews conducted throughout a several year data collection and analysis process. Forty-three northern Ontario Works program deliverers comprised of Ontario Works managers, supervisors, and caseworkers from across northern Ontario participated in the study. The analysis of the data reveals that northern Ontario Works program deliverers experience a multitude of resource constraints arising from local northern conditions as well as those situated within the welfare system. Research participants across northern Ontario reported that northern areas had limited economic capacity to provide adequate social services and infrastructure necessary to support the fulfillment of social assistance employment objectives. This study also found that social assistance employment objectives were compromised by limited local control over decision-making, under-resourcing within the Ontario Works program, and â urban-centricâ funding arrangements that disadvantaged northern areas. In addition, northern Ontario Works program deliverers reported substantive barriers to employment due to extremely low human capital among welfare recipients. Moreover, findings indicate that these constraints are compounding. In other words, northern Ontario Works program deliverers frequently encountered multiple and simultaneously occurring resource barriers. The result was described as intensifying resource deficiencies and inhibiting efforts to facilitate sustained labour market attachment among welfare recipients.
The Role of Ancient Liberty in Rousseau's Democratic Vision
Keywords: Democracy
Liberty
Montesquieu
Nationalism
Representation
Rousseau

This dissertation investigates Rousseau’s normative defence of democracy, beginning with his thoughts on the best kind of political practice. Despite recent attempts to highlight parts of his thought that are sympathetic to cherished liberal principles, current readers still struggle to defang what appear to be Rousseau’s populist excesses: his acceptance of majority-rule and his admiration for oppressive societies like ancient Sparta, Rome, or puritan Geneva. Rousseau defended a theory of legitimacy founded on individual consent, while characterizing the kind of politics practiced in these republics as normatively superior to all others. Motivated by this observation, the dissertation begins by investigating Rousseau’s thoughts on the institutions of republican Rome and Geneva. It concludes that his democratic vision has a very particular normative bent, which has hitherto been obscured by both liberal and collectivist readings. Rousseau’s political ideas suggest that a genuinely communal life is only possible where individuals participate actively in defending their interests. These interests are not abstract and uniform for all, but different and concrete. What Rousseau objected to was not individual interest as such, but a corrosive individualism founded on the belief that the concept ‘state’ is pure fabrication. This belief originates, and is nourished by, the alienation of legislative power to representative bodies. Rousseau’s defence of democratic participation, therefore, as well as his admiration for societies where citizens participated directly in the legislative process, are by no means secondary to his theory of consent. For such consent can only be known to exist where citizens participate continuously and directly in legislative assemblies. In this sense, Rousseau’s thought ought to be understood as inherently opposed to all forms of politics founded on a concept of the people that transcends (and is often alien to) the concrete and heterogenous reality that it is meant to signify.
Delicious: A History of Monosodium Glutamate and Umami, the Fifth Taste Sensation
Keywords: food science
Japan
monosodium glutamate
MSG
umami
United States

My dissertation examines two interrelated objects: the global commodity and flavour enhancer monosodium glutamate (MSG), and umami (roughly translated from the Japanese as “deliciousness”), the fifth basic taste that MSG is understood to confer. This project situates umami within transmutations of the life sciences between Japan and the United States, and shows how the metabolics of taste are inseparable from global capitalisms. My research demonstrates how the infusion of molecular technique into taste psychophysics, food technology, and emerging arenas like gastrophysics has provided a boon to corporate producers and commercial users of MSG, who have toiled since the 1970s to forge consensus around the scientific validity of umami taste and thus equate MSG—which crossed the Pacific as a food technology for improving troop morale after World War II—with ‘natural’ sources of umami. In the United States, MSG has been heavily coded as East Asian, despite the fact that it has been used pervasively in iconic Anglo-American food products (e.g. Campbell’s soup, flavoured chips)—and is even now bound up in the international branding of Japanese cuisine. I suggest that MSG’s implication in a ‘symptom complex’ (ranging from numbness and tingling to asthma and indigestion) may indicate that the additive’s metabolism by humans is less well understood than regulatory standards reflect—and that all umami tastants may not be metabolically equivalent. I argue that monosodium glutamate and similar umami-conferring additives not only help to make possible, they make palatable, the hegemony of ‘Big Food.’ MSG helps to make unhealthy, cheap foods taste good, and as such it illuminates the insidious appeal and potential spread of processed foods in an increasingly food-scarce world.
Introduction to Mexican Music for Solo Cello (1962-2014) from a Performer's Perspective
Keywords: Cello
cello solo
Mexican cello music
Mexican music
Mexican music for solo cello

This paper examines fifty-two Mexican solo cello works (and also three works written for two cellos, one written for cello and actor, and one written for cello and tape), all of which were acquired over a four-year course of research. All of these works were composed in the modern or avant-garde style between 1962 and 2014 and represent a lesser-known area of Mexican music. During the period from 2013 through 2014, eleven works were given to the author by Carlos Prieto, thirty-five works were obtained directly from composers, and five works came from library consultations during research trips to Mexico: at the National Library in Mexico City, at the National Center for Investigation and Documentation of Music in Mexico (CENEDIM), and at the National Center for the Arts in Mexico (CENART). Introduction to Mexican Music for Solo Cello (1962-2012) from a Performer’s Perspective documents an interdisciplinary approach to research: interactions and interviews with living Mexican composers, analysis and thoughts on interpretation of works by those composers, compilation of a list of works for solo cello written between 1962 and 2014 based on Adventure of a Cello by Carlos Prieto, Influence of Carlos Prieto on Contemporary Cello Repertoire by A.S. Saucedo Estrada, and the author’s research. The paper focuses on the vital contribution of cellist Carlos Prieto to the growth and proliferation of contemporary Mexican cello music. The paper includes documented interviews by the author with prominent composers and artists in Mexico including Carlos Prieto, Manuel de Elias, Ana Lara, Max Lifchitz, Samuel Máynez, Lucia Álvarez, Radko Tichavský, and Iracema de Andrade. This research is the first of its kind to document Mexican works for solo cello and to provide background analysis of these works from a performer’s perspective. All of the pieces covered in this project have yet to make a significant impact on the wider world or on professional cellists outside of Mexico.
Essays on Information Acquisition, Auction Design, and Persuasion
Keywords: Committee design
Heterogeneity
Informed principal
Persuasion
Reserve price
Voting

Chapter 1 studies how the composition and voting rule of a decision-making committee affect the incentives for its members to acquire information. Fixing the voting rule, a more polarized committee acquires more information. If a committee designer can choose the committee members and voting rule to maximize her payoff from the collective decision, she forms a heterogeneous committee adopting a unanimous rule, in which one member moderately biased toward one decision serves as the decisive voter, and all others are extremely opposed to the decisive voter and serve as information providers. The decisive voter is not identical to the designer. Chapter 2 studies mechanism design by a seller privately informed of the quality of an indivisible object. The privacy of the seller's information matters for mechanism design: selecting a mechanism that maximizes the seller's profit when her information is public is not incentive compatible for the seller when her information is private, as a lower-quality seller has an incentive to mimic a higher-quality seller. I show that reserve prices are the least costly device to separate higher-quality sellers from lower-quality ones. In equilibria that maximize the expected profit of every type of the seller among all separating equilibria, the lowest-quality seller adopts her public-information optimal mechanism, and each higher-quality seller adopts a mechanism that differs from her public-information optimal mechanism only in that the reserve prices are higher. Chapter 3 studies how a privately informed persuader should persuade a group of listeners if the listeners can imperfectly verify his information at a cost. Should he bring the listeners together and persuade them simultaneously or communicate with them sequentially? The answer depends on the verification costs of the listeners. Simultaneous persuasion outperforms sequential persuasion when it is not very costly for the listeners to verify the persuader's information. The opposite can be true if verifying the persuader's information is very costly. In sequential persuasion, it is optimal for the persuader to first approach the listener who is hardest to persuade. For both persuasion modes, in the persuader-optimal equilibria, the persuader pools extreme private information, and "truthfully reveals" moderate private information.
Superconducting Interfaces: Equivariant Solutions to a System of Nonlinear Wave Equations with Ginzburg-Landau Type Potential
Keywords: Calculus of Variations
Partial differential equations
Wave equations

In this thesis, we look for solutions to a two-component system of nonlinear wave equations with the properties that one component has an interface and the other is exponentially small except near the interface of the first component. The second component can be identified with a superconducting current confined to an interface. A formal analysis suggests that for suitable initial data, the energy of solutions concentrate about a codimension one timelike surface Γ whose dynamics are coupled in a highly nonlinear way to the phase of the superconducting current. We provide a rigorous verification of the predictions these formal arguments make for solutions with an equivariant symmetry in two spatial dimensions subject to a non-degeneracy condition. The contents of this thesis are based on the results presented in [32].
Budgeting and Psychological Motivations in Sales Management
Keywords: budgeting
lobbying
recognition programs
sales contests
sales force compensation
sales management

Sales force incentives are used to motivate, control, and reward salespeople, and represent a substantial expenditure for many firms. In this dissertation, I examine the role that sales managers play in setting budgets for sales force incentives and I investigate how public recognition of performance in sales contests (a common form of incentive) affects salespeople's motivations. The standard analytical models used in the literature on sales force incentives consist of a firm and a salesperson, with sales managers assumed (often implicitly) to be interchangeable with the firm. In my first study, I treat sales managers as distinct from their firms, in both their objectives and their information. I use this model to explore why many firms allow managers to participate in setting budgets for their salespeople's incentives despite the apparent conflict of interest that results. I show that allowing such participation can be beneficial when it reveals useful information about the manager's salesperson or their territory. I then propose a budget-setting approach that reveals such information and identify the conditions under which it is feasible and optimal. In my next study, I consider alternative solutions to the challenge of revealing a sales manager's private information about her salespeople or territories. In particular, I examine how the manager's own compensation can be designed for this purpose. This can be achieved by offering the manager a menu of contracts, each consisting of a compensation plan for the manager and a budget constraint within which the manager must design the salesperson's compensation plan. In my final study, a joint work with Tanjim Hossain and Mengze Shi, I use a combination of analytical modeling and laboratory experiments to investigate how a salesperson's psychological motivations re affected by the design of a sales contest. I am primarily interested in the public disclosure of contest results, such as the names and/or ranks of winners and losers. I find that recognizing winners generates positive psychological motivations, but that the relative performance of particular disclosure approaches can depend on the contest prize structure.
A Genome-scale RNA Interference Screen Identifies Novel Regulators of DNA Double-strand Break Repair
Keywords: Cell microarrays
DNA double-strand breaks
DNA repair
High-content screening
Homologous recombination
Microcephaly

All living organisms are continuously challenged by agents in their normal cellular environment that can inflict damage to their genetic material. DNA damage can have negative implications on cellular fitness by disrupting genomic processes such as DNA replication and gene expression. In addition, DNA lesions can lead to gene mutation and gross chromosomal rearrangements, events that are implicated in the development of cancer. DNA double-strand breaks (DSBs) are considered one of the most severe types of DNA damage. To protect genome integrity, organisms have evolved several DSB repair mechanisms. Homologous recombination (HR) is an essential DSB repair pathway that is of critical importance during the S- and G2-phases of the cell cycle. HR plays a central role in promoting genome stability and preventing tumourigenesis. For example, mutations in the genes coding for the HR factors BRCA1 and BRCA2 are responsible for familial breast and ovarian cancer. The limiting step in the HR pathway is the generation of single-stranded DNA (ssDNA) by DNA end resection. In this thesis, I describe the establishment of an immunofluorescence-based assay that monitors end resection by quantitative image-based cytometry (QIBC). Employing this assay, I conducted a plate-based RNA interference (RNAi) screen using a library that targets 18,452 genes. As expected, the top hits in my screen were known regulators of end resection including CtIP and all three subunits of the MRE11-RAD50-NBS1 (MRN) complex. I also outline the validation of one the strongest candidate end resection activators identified in the screen, the zinc finger protein, ZNF335. I demonstrate that ZNF335 promotes DSB repair by HR through the enhancement of DNA end resection. In the final chapter of this thesis, I describe the establishment of a cell microarray-based platform for conducting RNAi screens. The platform circumvents the long liquid-handling robotic procedures and large quantities of reagents that are common for plate-based screens.