VictorJuiz/thesis huggingface dataset:
Flow Consolidation for Congestion Control in Data Centers

Congestion control has been a fundamental component with evolving challenges in computer networks during the past few decades. In this thesis, we focus on the following key challenges of congestion control: lack of information sharing among flows, limited congestion visibility at the end-hosts, stringent requirements for convergence time, and dynamic and volatile nature of networks. We design a hierarchical congestion control system (HCC) that addresses the above challenges in data center networks. By grouping flows in a hierarchical manner, HCC enables flow cooperation and information sharing, leading to expanded visibility for flows, improved fairness, and faster convergence. Flows share congestion information within groups and propagate the compressed signals through the hierarchy, enabling aggregate control of multiple flows. HCC implements a distributed system for realizing max-min fairness, which is the theoretical objective of many congestion control protocols. To limit the state space, communication overhead, and processing time, HCC leverages flow aggregation and rate quantization techniques. Rate quantization is an effective way to reduce the run-time of max-min fairness. Flow aggregation helps flows to react collaboratively to changes at the edge of the network and converge to a local optimal state promptly. Also, the aggregated updates are propagated through the hierarchy to reach a globalmax-min fair state. This fast reaction at the edge is beneficial for short-lived flows and on-off traffic patterns. Moreover, to eliminate the volatile nature of flows, we define the correlation-aware flow consolidation problem. In correlation-aware flow consolidation, the goal is to reduce the fluctuations in individual flows by aggregating inversely correlated (or uncorrelated) flows. In our experiments, we show that we can reduce the average standard deviation of group demands by 33% which results in estimating future group demands with higher confidence. We evaluate HCC on a real workload and show that HCC converges to full utilization much faster (up to 4x), with a near zero bottleneck queue size, lower flow completion times (42 − 62%), and a significantly higher fairness index compared to well-known congestion control protocols. Also, by comparing HCC with a centralized solution, we show that HCC significantly reduces the overheads (by 73% and 99.5%).

Advisor: Ganjali, Yashar
Inflammasomes in the Intestinal Epithelium

Inflammasomes are multiprotein signalling complexes that detect a diverse range of pathological stimuli to activate inflammatory caspases, resulting in cell death and the release of IL-18 and IL-1. Inflammasomes are important in a wide range of diseases, in particular with auto-inflammatory disorders in humans. While they have been extensively studied in immune cells, their role in mediating inflammatory responses in other cellular compartments is ill-defined. It is becoming increasingly clear that epithelial inflammasomes are critical for controlling intestinal pathogens and regulating epithelial-mucosal homeostasis, little is known about how they function in this cellular compartment. Moreover, very few studies focus specifically on inflammasomes in human cells, and this has implications for our understanding of human diseases. In this thesis we investigate human intestinal epithelial inflammasomes in the two contexts that they are known to function: controlling epithelial-mucosal homeostasis and defending against cytosolic pathogens. We have uncovered that NLRP6 may function to regulate intestinal mucus homeostasis and that disruption of this may underpin the diseases of the microbiota-gut-brain axis. Secondly, we have uncovered the importance of the non-canonical inflammasome and caspase-4 in producing intestinal IL-18. Through this we have discovered a novel mechanism of GSDMD and propose that GSDMD regulates the activity of caspases in the intestinal epithelium. Together these data expand upon the knowledge of innate immune signalling in the human intestinal epithelium, enhancing our understanding of how inflammasomes contribute to defense against pathogens and regulation of the intestinal microenvironment.

Advisor: Girardin, Stephen E
Philpott, Dana J
A Preclinical Evaluation of High-pressure Processing on Pathogen Inactivation, Biological and Immune Protein Activity, and in Vitro Digestibility of Donor Human Milk

Background: Although donor human milk is the preferred supplement for preterm infants over formula, Holder pasteurization (HoP) negatively impacts bioactive components, minimizing its benefit and likely contributes to the slower growth of recipient infants. High pressure processing (HPP), better preserves nutrients and bioactive components compared to HoP. It is unknown whether viruses are inactivated, if HPP impacts protein digestibility and whether preserved immune proteins retain functionality upon digestion.Objectives: (1) To determine if HPP could inactivate enveloped and non-enveloped viruses in a human milk matrix and (2) To determine the impact of HPP versus HoP on the formation of high molecular weight protein aggregates, subsequent protein digestibility and bioactive function throughout simulated preterm infant digestion. ii Methods: First, milk pools (N=10) from individual donors or media controls were inoculated with cytomegalovirus, typically found in milk donations, or hepatitis A virus, used in virucidal testing, then treated with HoP or with HPP (350, 500 or 600 MPa, 8/10 min). Plaque reduction assays were used to assess infectivity and lactoferrin measured via high performance liquid chromatography as a quality indicator. Second, pools of donor milk (N=3) each containing milk from 3 unique donors, were processed via HoP or HPP (500 MPa, 10 min) were digested using a dynamic in vitro model mimicking the preterm infant gastrointestinal physiology. Protein digestion was assessed by crude protein (bicinchoninic acid), protein composition (native/reduced PAGE), particle size distribution (dynamic light scattering) and lysozyme activity (turbidimetric assay). Results: HPP at 500 MPa for 8/10 min was not different from HoP in inactivating virus; however, HPP retained a significantly higher proportion of native lactoferrin. Compared to raw milk or HPP, milk treated by HoP led to increased lactoferrin proteolysis and milk fat globule associated proteins. Lysozyme activity was better maintained in raw and HPP-treated milk compared to HoP. HoP and HPP produced protein aggregates: no meaningful differences were observed throughout digestion, including for particle size distribution. Conclusions: A safe and higher quality supply of donor milk with preserved innate function could be produced should HPP replace HoP. Emerging differences in protein digestibility, and resistance of key proteins to digestion support HPP as a promising alternative.

Keywords: Bioactive proteins
Donor human milk
High pressure processing
Simulated digestion
Viral inactivation
Advisor: O'Connor, Deborah L.
Unger, Sharon
Investigating the Mechanisms of Perinatal Neuron Degeneration, Survival, and their Differentiation from Neural Precursor Cells of the V-SVZ

For the formation and maintenance of functional neuronal networks, the generation of neurons from their progenitors developmentally as well as their continued survival once the circuitry has been established are both crucial for nervous system homeostasis and plasticity, with disruptions resulting in neuropathologies. For the integrity of this process, first, cellular mechanisms need to temporally orchestrate the correct neuronal fate delineation from multipotent precursors and second, transduced pro-life signals need to suppress degeneration-promoting transcriptional programs to ensure continued survival. In this thesis, I describe a novel 4E-T-based translational regulation mechanism that “fine-tunes” the timing of neurogenesis, coordinating the correct emergence ofinterneurons from transcriptionally pre-fated early postnatal precursors (Chapter 5), in addition to characterizing a novel neuroprotectant promoting survival by suppressing the degeneration of peripheral neurons and potently protecting axonal mitochondria (Chapter 4). Postnatal precursors which possess multi-lineage potency and the ability to renew long-term, are a continuous source of neuronal progeny for tissue formation and repair, and must balance their maintenance through self-renewal, expansion of their pools through proliferation, and the need to generate progeny through differentiation. In Chapter 5 of this thesis, I demonstrate that postnatal precursors are “pre-fated”, expressing neuronal differentiation instructing specifier transcripts, and that a 4E-T-based regulatory mechanism involving translational repression modulates protein synthesis levels of these mRNA targets, controlling timely neurogenesis. Established peripheral neurons and their axonal projections need to then be preserved for the lifetime of the organism to ensure proper circuit function. One goal of the work presented in this thesis is to identify safe-in-man drugs that can block or delay axon degeneration, and to use these drugs to characterize new degeneration pathways. To this end, the work described in Chapter 4 describes and identifies the multikinase inhibitor Foretinib as being protective in sympathetic, sensory and motor neurons across multiple degeneration paradigms. Thus, my thesis traces the trajectory of neurons in two main aspects of neurobiology: from onset of fate commitment and appropriate neuronal lineage acquisition, to maintenance and protection in maturity once neurons integrate into circuits, highlighting the consequences to the organism in the case of aberration in either process.

Keywords: Degeneration
Neurodevelopment
Neurons and glia
Neuroprotectant
Stem cells and neural precursors
Translation and translational repression
Advisor: Miller, Freda D
Kaplan, David R
Characterization and Design of Nickel-binding Proteins towards Metal Recovery Applications

Nickel is an important metal in the adoption of greener technologies needed to transition to cleaner economies, and mines face pressure to source it more sustainably. Nature has evolved nickel-specific ATP-binding cassette (ABC) importers that can transport nickel across a cell’s membrane from the environment into the cytoplasm. Specifically, their solute-binding component known as the nickel-binding protein (NiBP) scavenges the cell’s periplasmic space to deliver metals to the cognate permease complex for transport. Existing methods for metal-binding characterization are not amenable to protein engineering efforts that rely on screening libraries of variants with different substrates. Using natural changes in protein fluorescence during a metal-binding event, we first optimized an assay previously reported in literature to measure the binding affinity (K¬D) of NiBP complexes with nickel and other metals. This assay was validated by determining the KD of the well-characterized NiBP CjNikZ from Campylobacter jejuni, which was comparable to reported values, so it was then used to demonstrate the presence of Ni(II)-binding activity in the uncharacterized NiBP called CcNikZ-II from Clostridium carboxidivorans. Next, we determined the crystal structure of CcNikZ-II, which revealed the potential Ni(II)-binding site located close to a short variable loop. Mutagenesis identified the CcNikZ-II residues involved in Ni(II) binding, but the role of the variable (v-)loop of this protein (TEDKYT) remained unclear. We purified nine CcNikZ-II homologues and determined the nickel-binding affinity of these proteins using an intrinsic fluorescence quenching assay, which showed all these proteins have higher KD for Ni(II) than CcNikZ-II. Furthermore, we replaced the CcNikZ-II v-loop sequence (TEDKYT) with those from the other homologues with higher affinity and found that the engineered CcNikZ-II variants have a higher binding affinity to Ni(II). Metal promiscuity screening further demonstrated the importance of the secondary coordination sphere in controlling affinity and specificity. Finally, an engineered E. coli strain (Ni_v.1) was created and tested in 10 ppm NiCl2 solution matching environmental conditions and demonstrated 7-fold improvement in nickel bioaccumulation performance compared to controls. Thus, both wildtype and engineering microbial NiBPs can be engineered for improved metal binding and selectivity and used for developing bio-based technologies for metal recovery applications.

Keywords: ABC transporters
biomining
high-throughput screening
metal binding
metal recovery
solute-binding proteins
Advisor: Yakunin, Alexander F.
Mahadevan, Radhakrishnan
Leveraging Twitter Data and Activists’ Lived Experiences to Explore Digital Advocacy for Sex Work Decriminalization in the United States

Contemporary community activism has been greatly influenced by the wide adoption of digital technologies, such as the use of social media. For communities whose voices are often systemically marginalized in public discourse, social media affords unique opportunities for communication to mobilize for social and policy advocacy. The digital space, meanwhile, has yet to be made equitable for all. This dissertation explores Twitter-based digital advocacy for sex work decriminalization in the United States, focusing on the opportunities in the digital space for community activism, the barriers facing activists when using Twitter for advocacy, and the resistance demonstrated by community activists in navigating barriers. Theoretically, the dissertation is guided by resource mobilization theory, discursive structure theory, the theory of connective action, and a systemic lens of digital inequity. This dissertation consists of five chapters, including an introduction, three independent empirical manuscripts, and a conclusion. Paper one adopts a sequential mixed methods design to explore how activists use Twitter connective functionalities (e.g., following a Twitter user, mentioning a user in a tweet, and replying to a user) to connect with key stakeholders and organize for sex work decriminalization. The mixed method analyses integrate findings of social network analysis of Twitter data and qualitative content analysis of interviews with activists who use Twitter for decriminalization advocacy. Paper two adopts qualitative content analyses of both tweets and qualitative interviews with activists to explore how sex worker rights activists and advocacy groups build Twitter messages to mobilize for decriminalization and how online advocacy is connected to offline advocacy. Finally, paper three adopts a qualitative content analysis of interviews with activists to explore how digital inequity shapes the barriers facing activists and how activists navigate and resist barriers. Overall, this research reveals activists’ intentional and strategic use of Twitter to organize resources, build movement alliances across political and social justice domains, and bridge online and offline mobilization for decriminalization advocacy. Meanwhile, the findings raise concerns about how intersecting forms of systemic marginalization legitimize platform-embedded exclusions, making Twitter an inequitable and risky environment for activists, especially for activists who engage in both online sex work and digital activism, to organize for advocacy. The research suggests the need for social workers and social justice researchers to critically examine and engage with the complex role of social media in community activism and the significance of conducting advocacy for digital equity with a commitment to confronting and removing structurally inequitable conditions compromising the digital participation of marginalized communities.

Advisor: Newman, Peter A
Excellence and Access for Ontario’s Higher Education System: How Universities Commit to Both

This thesis describes two phases that together investigate how the 20 Ontario universities commit to the values of widening participation and academic excellence, which are often viewed as competing. This research employs theories and concepts at the intersection of sociology and politics of education, namely, maximally maintained inequality, effectively maintained inequality, isomorphism, and legitimacy to compare Ontario to international trends of social stratification and inequality within the higher education sector. Phase 1 provides a landscape analysis of Ontario’s higher education system and a classification of Ontario’s universities as recruiting or selecting. The universities were classified using three sources of data. The first was the entering grade-point averages across universities and programs from Common University Data Ontario (CUDO), the second was a discourse analysis of websites for five programs (Arts, Science, Business, Engineering, and Nursing) at each university, and third was Maclean’s (a Canadian current affairs magazine) rankings of university reputation. Phase 1 found that certain Ontario universities were distinctively selecting across most programs, while others were recruiting across most programs, and that the majority of Ontario universities had both selecting and recruiting programs. In phase 2, I conducted a discourse analysis of guiding documents (Strategic Mandate Agreements and Strategic Plans), and discourse analysis of publicly facing websites and viewbooks to explore how two of Ontario’s selecting universities and two recruiting universities commit to both widening participation and academic excellence. The findings reveal that Ontario’s selecting universities and programs prioritize being perceived as academically excellent (e.g., rigorous training, prestigious learning opportunities, leading innovation, and impact) on a global stage. Recruiting universities prioritize widening participation for local communities through strong recruiting and retention discourse and local community building through research. Recruiting and selecting universities use the discourse of academic excellence and widening participation to establish cognitive, moral, and pragmatic legitimacy. Selecting universities commit to widening participation to the extent that it does not challenge perceptions of global academic excellence. The findings of Phases 1 and 2 are relevant for policymakers, researchers, university leaders, and the public, as Ontario’s differentiated higher education system is not removed from the debate around equality of opportunity.

Keywords: academic excellence
access
differentiation
equity diversity inclusion
strategic mandate agreement
widening participation
Advisor: Childs, Ruth A
Modification of Macrocyclic Backbone to Control Conformation and Reactivity

Macrocyclic peptides are a valuable medicinal tool for drug discovery purposes as they are more effective at targeting protein binding sites and have better proteolytic stability than linear peptides and small molecules. However, drawbacks, such as their oral bioavailability and cell permeability, hinder the development of cyclic peptides into therapeutics. Many recent investigations focus on trying to design cyclic peptides for a specific conformation to enhance target-binding and to resolve cell permeability issues. In this dissertation, different amide isosteres were explored and incorporated into the backbone of macrocyclic peptides to observe the conformational outcome upon altering the backbone and to assess their permeability. In chapter 2, subtle peptide bond isostere, the amidine functionality, was site selectively incorporated in cyclic pentapeptides using the thioamide functionality. The addition of the amidine functionality allows for switching between a hydrogen bond donor to hydrogen bond acceptor. This feature was utilized to assess the role of H-bonding interaction in determining the conformation. By employing the amidine as a conformational probe, we revealed the insignificance of H-bonding in the conformation of cyclic pentapeptides in which steric interactions of side chains and turn-inducing residues have a larger influence on the conformation. In chapter 3, further investigation was performed on the 1,3,4-oxadiazole-embedded macrocyclic peptides. Assays that are more representative of cell membranes showed high cell penetrating ability. However, passive permeability was not exhibited by these oxadiazole macrocycles. These findings have demonstrated that the design of macrocyclic peptides for cell permeability is a complex matter and that ct-incorporated oxadiazole macrocyclic peptides may provide a framework for designing cyclic peptides which can undergo active transport permeation. In chapter 4, we have repurposed the rarely used Cornforth rearrangement to induce sub-residual ring contraction in peptide macrocycles. Investigation of the rate of the reaction as well as the conformational consequences upon rearrangement was performed. Distal changes of the dihedral angles were observed because of coupled bond rotations. Furthermore, a flexible macrocycle has shown conformational rigidity upon rearrangement, which could facilitate conformation-activity studies.

Advisor: Yudin, Andrei
Teachers’ Gender, Emotions and Needs in K-12 Public Education in Saudi Arabia

The present study investigates teachers’ professional experiences, emotional lives and needs, focusing on how gender impacts and shapes these experiences in K-12 public education in Saudi Arabia. The literature on teacher professional preparedness globally highlights important local and national aspects of K12 teaching and learning. Yet research on K12 public education in the Middle East, especially Saudi Arabia, lacks attention and deeper understanding of how self-identified male and female teachers experience their professional environments and relate to students, school administrators, parents and school staff. This study helps to fill that knowledge gap. It uses 10 semi-structured personal interviews with teachers in urban schools in Saudi Arabia to study the importance of emotions and emotional labour in their careers and lives. Findings from the interview narratives highlight two important aspects of teachers’ professional lives: both male and female teachers fear state and school authority and institutional power; yet female teachers also struggle with and resist patriarchal norms and structures that impact how they relate to their students, and navigate the controlling gaze of school principles and colleagues. The conclusions propose and construct a professional training program for Saudi K-12 teachers and principals, promoting their emotional awareness as a way to foster positive relations and experiences for all participants in K-12 education. The program’s objectives and content are described and rationalized in the last chapter of the thesis. The program is a concrete praxis that could be applied in any K-12 educational environment in Saudi Arabia. The program is also a unique contribution to public education in Saudi Arabia, where programs focused on emotional and professional wellbeing, gender-based awareness and social relations in education currently do not exist.

Advisor: Todorova, Miglena