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Investigating the Role of Protein Kinase R in the Host Immune Response to Bacterial Infection
No full textProtein Kinase R (PKR) was originally identified as a host protective kinase in response to viral infections. However, PKR was later discovered to play diverse roles in regulating cell signaling, such as inflammation, cell proliferation, and cell death. Recently, there are emerging reports by our lab and others that PKR is also involved in the immune response to bacterial pathogens, including Mycobacterium tuberculosis. However, there are conflicting reports on the role of PKR in the host immune response to different bacterial infections. In this thesis, I show that Listeria monocytogenes (Lm) infection triggers upregulation of PKR expression and increases its activity, as indicated by increased phosphorylation of PKR. Using genetically manipulated macrophages, I show that PKR overexpressing THP-1 macrophages (THP-PKR) promote increased Lm survival and proliferation, while deletion of PKR (THP-ΔPKR) reduce bacterial survival. Furthermore, I demonstrate that enhanced growth of Lm in THP-PKR cells is mediated through type I IFN signaling, as inhibition of the Interferon α/β receptor (IFNAR) restored the ability of THP-PKR macrophages to control Lm growth. Consistent with this observation, immunological profiling of THP-PKR cells indicates an increase in the production of IFN-β and IL-10, and a reduction in TNF-α production. Interestingly, while Lm infection induces cell death in THP-1 macrophages, there were no PKR-dependant differences in cell death observed. In search for a potential functional mechanism, I showed that the effect of PKR on Lm survival was not mediated through modulations of autophagy signaling or changes in reactive oxygen species (ROS) production. However, PKR-mediated survival of Lm can be perturbed by the addition of interferon gamma (IFN-γ), which reduces Lm survival in THP-PKR macrophages to the level of the control cells. This suggests that the functional mechanism of PKR in the context of Lm infection is at least partially mediated through an IFN-γ dependent pathway. Thus, this project aims to highlight the importance of PKR signaling and regulation for the host defense against pathogens
Bullying Victimization and Mental Health Among Canadian Gender and Sexually Diverse Youth: A Replication and Expansion of Previous Studies
No full textGender and sexually diverse youth disproportionately experience bullying and emotional problems. However, small samples and limited intersectional research have hindered our understanding of this vulnerable population. In the present study, the moderating role of gender identity and sexual orientation in the relation between bullying victimization and emotional problems was examined in a large sample of Grade 7–12 Canadian students drawn from the Health and Peer Relations Study (N = 6,824; racial/ethnic minority = 38.7%; sexually diverse = 29.8%; gender diverse = 5.3%). Controlling for race/ethnicity and grade, there was no three-way interaction among bullying, gender identity, and sexual orientation, nor a two-way interaction between bullying and gender identity. However, a significant bullying by sexual orientation interaction emerged, wherein bullied sexually diverse youth reported more emotional problems than their non-bullied sexually diverse peers and bullied straight youth. A gender identity by sexual orientation interaction was also found where sexually diverse girls had worse mental health compared to sexually diverse boys and sexually-gender diverse youth endorsed more emotional problems than sexually diverse girls and boys. Overall, sexually diverse youth who were bullied by their peers and gender diverse youth, particularly those identifying as sexually diverse, reported significant mental health challenges. These results support minority stress and intersectionality models and highlight the need for anti-bullying and mental health initiatives. Future research should further explore intersectional variations and contextual factors contributing to these disparities
Phase-Field Crack Simulation for Thermomechanically Coupled Problems
No full textIn the past several decades, the community of computational solid mechanics has devoted a lot of efforts to develop robust and accurate numerical methods to model fracture initiation and propagation. Some of the prominent methods include the cohesive zone model, the embedded discontinuity approach, and the extended finite element method approach. However, these earlier methods either suffer from pathological mesh-dependence or rely on heuristic fracture tracking algorithm to track crack propagation. These tracking algorithms cannot robustly handle complex crack geometries such as merging and branching even in 2D problems, not to mention complex 3D crack surfaces. Recently, the phase- field method (PFM) has drawn more and more attentions for simulations of crack propagation in solids due to its capability of naturally handling complex crack patterns such as merging and branching. In the view of energy functional, the PFM converts the sharp crack problem into a constrained optimization problem possessing a variational structure. The PFM constructs a nonlinearly coupled problem between the displacement eld and the phase-field, which can be solved by either the staggered approach or the monolithic approach. In this thesis, algorithms for both approaches are adopted, which respectively rely on the alternate minimization (AM) and the limited-memory BFGS (L-BFGS) scheme. These two algorithms can both overcome the
convergence issues caused by the non-convex nature of the energy functional in fracture mechanics. The PFM algorithms are further combined with heat conduction problems to model the crack propagation under thermomechanically coupled loads. Several numerical examples, including crack simulations in the quenching problem and the thermal barrier coating problem, are provided to demonstrate the capabilities of the developed method. The limitation of current model and possible solutions in future research are discussed
Decoding the impact of environmental shifts on snail density dynamics in the Yangtze River basin: a 26-year study
No full textAbstract Background With the intensification of climate change and human engineering activities, environmental changes have affected schistosome-transmitting snails. This study explored the influence of environmental changes on the evolution of snail populations. Methods Data from annual snail surveys and related factors such as hydrology, temperature, vegetation, etc., on nine bottomlands from 1997 to 2022 were collected retrospectively from multiple sources. Interpretable machine learning and the Bayesian spatial-temporal model assessed the relationship between environmental change and snail density. Results Between 1997 and 2003, mean snail density was in a high-level fluctuation stage. From 2003 to 2012, it declined significantly from 0.773/0.1 m2 to 0.093/0.1 m2. However, it increased by 27.6% between 2013 (0.098/0.1 m2) and 2022 (0.125/0.1 m2). Since operation of the Three Gorges Dam (TGD) began in 2003, the duration of bottomland flooding decreased from 122 days (1997–2003) to 57 days (2003–2012) and then rebounded in 2012–2022, which was noticeable in the Anhui Section. The ground surface temperature and night light index of the bottomlands increased from 1997 to 2022. After adjusting for confounding factors (e.g. rainfall, temperature, and vegetation), the relative risk (RR) of increased snail density rose with flooding duration of between 20 and 100 days but decreased with flooding duration of > 100 days. Snail density showed an “L”-shaped relationship with the night light index, and the RR of increased snail density was lower at a higher night light index. Compared with bottomlands in the first quartile cluster of ground surface temperature, bottomlands in the second, third, and fourth quartile clusters of ground surface temperature had higher snail density RR values of 1.271 (95% CI 1.082–1.493), 1.302 (95% CI 1.146–1.480), and 1.278 (1.048, 1.559), respectively. Conclusions The TGD lowered the water level and flooding duration, which were not conducive to snail population growth. However, over time, the inhibitory effect of the TGD on snails may have been weakening, especially in areas far from the TGD. In recent years, the rebound of snail density may have been related to the rise in water levels and the change in the microenvironment. Establishing an efficient monitoring and response system is crucial for precisely controlling snails. Graphical Abstrac
Recontextualizing Ibn Khaldun: A Meta-Theoretical Study of Khaldunian Thought
No full textPostcolonial studies and decoloniality have consistently questioned the colonial matrix of power upon which much of our modern world is established. This generated a desire to create a more pluralistic social sciences by rehabilitating non-Western knowledges previously deemed incompatible with the Cartesian epistemological and ontological model. The purpose of this theoretical thesis is to discuss the restoration of Ibn Khaldun’s theory. Extensive studies have sought to explain and interpret Ibn Khaldun’s work from different perspectives. What all of those studies have in common is their utilization of different approaches, all rooted in the Cartesian epistemological and ontological model. This lack of epistemic pluralism led to a crippling stagnation of the contemporary studies on Ibn Khaldun, which seem to have hit a glass ceiling. According to Syed Farid Alatas, the current leading figure of Khaldunian revivalism, a methodical restoration of his theory needs to be undertaken in order for Ibn Khaldun to be incorporated into the corpus of contemporary sociology. More studies need to focus on examining the various aspects of Khaldunian thought in order for a neo-Khaldunian sociology to emerge. The content of the Muqaddimah must be reinterpreted through a recontextualization of Khaldunian though within the wider landscape of Islamic erudition. I decided to move past the usual descriptive accounts of Ibn Khaldun’s work and concentrate instead on an analysis of the theory he detailed in his magnum opus, his Kitab al-‘Ibar featuring the Muqaddimah. By exploring the European reception of Ibn Khaldun’s work, I lay bare the reading grid that emerged from the interpretation of his work within Western academia; a reading grid through which the Muqaddimah continues to be interpreted and understood. This thesis is a meta-theoretical study of Ibn Khaldun’s ‘ilm al-‘umran al-bashari (science of human social organization), which proceeds to a recontextualizing and a repositioning of Khaldunian thought. The studies pertaining to Ibn Khaldun tend to focus solely on two elements of his thought that he described in the Muqaddimah, the passage from a primitive social organization to a civilized one, and the rise and fall of dynasties. However, the other aspects of his theory, such as his understanding of leadership through the concept of ‘asabiyyah, as well as the changes inherent to the transfer of power down the generational line, are for the most part ignored. The goal of this exploration of Khaldunian thought is to transcend the usual reading grid through which the Muqaddimah is often read and interpreted. To do so, this thesis explores the political ideas at the heart of Ibn Khaldun’s theory of state formation, as well as the historical context and the intellectual tradition which fostered the emergence of Khaldunian thought
Designing a trauma informed service to deliver trauma therapy with people experiencing homelessness: a qualitative study
No full textAbstract Background People who are homeless experience an increased prevalence of traumatic events, including childhood trauma, trauma related to being homeless, and structural trauma. It is important to consider trauma in the delivery of health services for this population. Using a trauma-informed care approach is one way to ensure that a service or program takes into consideration the effects of trauma. The aims of this study are to describe how best to design a service to engage people experiencing homelessness in a trauma-focused therapy as well as detail what trauma-informed care would look like in this setting. Methods We conducted a series of qualitative interviews about how to design a trauma-informed trauma therapy for people experiencing homelessness and their perspectives on different principles of trauma-informed care. Thematic analysis was used to identify, analyze and report themes identified in the data. Results We conducted 12 in-depth interviews (8 women, 4 men) with people who were currently peer support workers with lived experience of trauma and homelessness. We identified themes to design a trauma-informed service including low-barrier access, communication strategies, meeting people’s needs, and how to engage and retain people in the service. We also identified themes related to how people with lived experience understand the principles of trauma informed care. Discussion The findings from this study provide insight and practical recommendations for designing and implementing a trauma-informed therapy tailored for people experiencing homelessness. The findings here shed light on the lived experience perspective of trauma-informed care principles, adding nuance to our understanding of what it means to be trauma-informed
Feasibility and acceptability of a parallel, two-arm randomized controlled trial to evaluate an online physical activity behavior counseling intervention for young adults diagnosed with cancer: a mixed-methods pilot study
No full textAbstract Background Physical activity (PA) benefits young adults living with and beyond cancer, yet participation remains low. This pilot randomized controlled trial (RCT) evaluated the feasibility and acceptability of a PA behavior counseling intervention for young adults post-cancer treatment and trial methods. Methods A mixed-methods, open-label, parallel, two-arm pilot RCT was conducted with young adults recruited nationwide (Canada) by healthcare provider referral or advertising. Eligible participants were 18–39 years (with a first diagnosis of invasive, non-metastatic cancer at age 18–39 years), had completed active treatment for invasive, non-metastatic cancer < 5 years prior, self-reported < 150 min of moderate-to-vigorous intensity PA weekly, were fluent in English, and had access to/computer literacy for videoconferencing technology. Young adults were randomized to receive a 12-week individualized PA behavior counseling intervention delivered via videoconferencing technology by PA counselors or usual care. Informed by self-determination theory, the intervention emphasized autonomy support and applied motivational interviewing. Staff tracked feasibility and acceptability outcomes regarding enrollment, allocation, retention, adherence, and adverse events. Young adults and PA counselors were interviewed post-intervention (T1; primary endpoint) and at trial completion, respectively. Planned efficacy outcomes were assessed using accelerometers and online surveys at baseline (T0), T1, and follow-up (T2; secondary endpoint; 24 weeks post-baseline). Results Seventy-four young adults were screened for eligibility (recruitment rate ~ 4/month over 18 months); 47 (63.5%) were eligible, of which 42 (89%) consented, completed T0 assessments, and were randomized. Most (75% [15/20]) allocated to receive the intervention completed all sessions. Retention rates were 85.7% (T0 to T1 [36/42]) and 71.4% (T0 to T2 [30/42]). Analyzable data for the primary efficacy outcome (PA behavior) were available for 57.1% (24/42) at T1. Content analysis of interviews with 35 (80.0%) young adults and both (100.0%) PA counselors yielded three themes reflecting factors that positively impacted intervention acceptability and one theme reflecting factors that negatively impacted the trial methods’ acceptability, as well as recommendations to optimize the trial methods and intervention. Conclusions The trial methods and intervention were largely feasible and acceptable for young adults post-cancer treatment, although modifications are required to optimize recruitment strategies, enhance retention at follow-up, refine the intervention, and reduce missing data. A full-scale RCT to assess the efficacy of the intervention and estimate concomitant costs is warranted. Trial registration ClinicalTrials.gov (ID: NCT04163042). Registered on November 14, 2019.
Mitochondrial Antiviral Signaling Protein (MAVS) in Post-MI Cardiac Remodeling
No full textBackground: Mitochondrial Antiviral Signaling Protein (MAVS) is an innate immune effector protein uniquely residing on mitochondrial surfaces. Previously, we identified MAVS as a key regulator of cardiac remodeling, inflammation, and metabolism in murine models of pressure-induced heart failure. This current study investigates MAVS in myocardial infarction (MI), hypothesizing a key role in cardiac stress responses. Methods: Utilizing left anterior descending artery (LAD) ligation, we induced MI in Mavs⁻ᐟ⁻ and WT mice to assess remodeling, function, and molecular changes. Results: Male Mavs⁻ᐟ⁻ mice exhibited reduced MI-induced hypertrophy, preserved ejection fraction, and diminished heart failure markers compared to WT controls. Several notable sex-based variations indicate MAVS functions in a sex-specific context. Impact: Our findings indicate that MAVS may be a critical regulator of cardiac hypertrophy and remodeling post-MI. This research underscores the potential for targeting mitochondrial activity-based pathways to improve post-MI cardiac remodeling, with MAVS as a possible candidate
Intelligent Data-Planes for Network Traffic Management
No full textNetwork traffic management is increasingly complex due to the exponential growth of connected devices and bandwidth-intensive applications. As the volume of network traffic continues to rise, managing this data flow efficiently is a key challenge for modern communication networks. Traditional management techniques, which rely on static, protocol-driven methods, struggle to keep pace with the dynamic demands of today’s networks. Emerging technologies like software-defined networking (SDN) and machine learning (ML) offer promising solutions by enabling more intelligent, real-time network management. However, in traditional ML-assisted SDN architectures, ML models are deployed in the control-plane, which relies on receiving relevant traffic information from the data-plane for analysis. This design poses a key limitation, as frequent control-plane/data-plane communication introduces latency that can delay time-sensitive services such as congestion mitigation and intrusion response. This thesis addresses this challenge by proposing a novel approach: introducing ML directly into the data-plane to enable real-time, autonomous decision-making, thus reducing the delays associated with traditional SDN architectures.
The primary objective of this research is to design and implement an intelligent data-plane with built-in ML inference, enabling real-time, local decisions and reducing reliance on the control-plane. First, we develop a quantization-aware ML toolbox that facilitates the training of ML models while simplifying their storage and execution within resource-limited data-planes. This approach ensures that quantized model inference can be effectively implemented in the data-plane, satisfying its operational and computational constraints. Second, to enable multi-phase decision-making within the data-plane, we design a confidence-based intrusion detection system that detects malicious flows at both early and later phases by leveraging the confidence level from early detection. Third, to support concurrent management tasks, we develop a novel in-network multi-task learning framework that performs simultaneous inference for multiple tasks in the data-plane. This approach is both resource-efficient and more accurate than single-task models by sharing feature representations among related tasks. Additionally, we enhance scalability by supporting distributed deployment, where different layers of a multi-task model can be offloaded across multiple switches. Finally, we address the challenge that offline trained models often struggle to adapt to dynamic network environments, where changing traffic patterns can degrade performance. We design an unsupervised drift detection mechanism in the data-plane that monitors distributional changes in traffic and triggers model updates when drift is detected. In addition, we present an in-network drift-aware traffic classification framework that not only classifies known traffic accurately but also identifies drifting samples that deviate from all known classes
Measuring Lexical Distance between Parallel Corpora: The Case of AI-Generated News Translation
No full textThis is an Accepted Manuscript of an article published by Taylor & Francis in Perspectives: Studies in Translation Theory and Practice, on 25 Nov 2025, available at: https://doi.org/10.1080/0907676X.2025.2590066.Since the University of Warwick's news translation project in the mid-2000s, it has been a truism that journalists rarely translate whole articles but instead compose stories using texts in other languages as one source among others. However, the development of AI-based machine translation has brought about a shift in journalistic practices. Increasingly, multilingual news agencies are using these tools to produce similar stories in multiple languages. One consequence has been that researchers can now compile parallel corpora of translated stories. This article proposes a method to characterize such corpora by measuring the distance between source and target texts, a method it applies to stories published in English and French on the website SwissInfo.ch. It describes the mechanics of corpus-building, article vectorization, and the creation of a lexical substitution list that makes measurement possible. It then proposes three measures -- Euclidean, Jaccard, and cosine -- which have complementary strengths and weaknesses. The value of these measurement tools is heuristic: they make it possible to identify patterns that can be investigated using other methods more familiar to news translation researchers, such as interviews or direct observation.This project was undertaken thanks to funding from IVADO and the Canada First Research Excellence Fund