University of Toronto
  • Toronto, ON, Canada
Recent publications
There is a strong connection between water supply and energy consumption which, considering trends towards reducing system stresses, provides an opportunity to take advantage of the synergies associated with leakage reduction and energy conservation. In recognition of these synergies, a multi-year project has been initiated in Ontario through funding from the province’s Independent Electricity System Operator to promote water loss reduction practices. The project involves the development and deployment of a mobile testing unit designed as an affordable method to accurately and reliably measure minimum night flow (MNF), an indicator of leakage, into discrete sectors of water distribution systems commonly referred to as district metered areas (DMAs). In addition to flow monitoring, the mobile unit is equipped with a pressure reducing valve (PRV) to directly test the effectiveness of pressure moderation on leakage reduction. More broadly, the project involves the collection of data across 22 DMA sites in Ontario with results informing the development and application of evidence-based benchmarking metrics used to assess the performance of DMAs in similar municipalities elsewhere. Moreover, analyses of the project’s testing results, previous DMA work and advanced metering infrastructure (AMI) data are presented to support the establishment of MNF benchmarks (representing healthy systems). While this project is still ongoing, initial successes have proven the mobile testing unit concept and substantial value has already been realized. Accordingly, a case study is featured where exceptional savings were demonstrated and quantified as a result of intervention efforts informed by the project.
Current design standards for steel structures in North America use a structural reliability model that employs first-order probability methods. This approach yields interpretable safety indexes and corresponding probabilities of failure, based on a log-normality assumption for the load and resistance probability distributions. In this work, the suitability of a log-normal assumption for the resistance distribution is assessed numerically by constructing approximate distributions of the ultimate limit state resistance of various welded steel connections between rectangular hollow section (RHS) members. Raw data from material surveys and experimental results are combined to produce approximate resistance distributions for RHS X-connections, under branch axial compression and for a variety of geometric scenarios. It is empirically shown that resistance distributions are often well represented by log-normal distributions, despite deviations in laboratory results. This suggests that current reliability analyses, as prescribed by first-order methods such as in CSA S408-11, are adequate for a wide range of resistance models for steel members and connections, even for moderate violations of assumptions in experimental or numerical data.
Organizational Design and Management (ODAM) elements of Ergonomics and Human Factors (E/HF) apply to congress organization. Exemplary delegate and organizer E/HF experience is constrained by shifting requirements, time pressures and financial constraints. E/HF application while organizing the International Ergonomics Association's Triennial Congress in 2021 (IEA2021) is described focusing on delivery platforms considering typical and exceptional (pandemic) constraints, emphasizing ODAM E/HF principles and generalizable lessons. Post-Congress feedback from delegates, session chairs and Congress organizers reveal the Congress as experienced. Presenting virtually allowed on-demand recording access following live sessions and increased question-and-answer flexibility. Frustrations included navigating multiple platforms and insufficient communications. Stakeholders’ differing expectations increased organizer workloads and delegate frustration. Maximum virtual presentation benefits require efforts to ensure integrated, human-centered platform development. Simply digitizing traditional Congress sessions ignores potential enhancements. Embracing innovations would help meet delegate communication needs via careful selection and deployment of evolving virtual meeting technologies. Organizational learning strategies can support these efforts.
Anthropomorphization occurs when human characteristics are attributed to nonhuman animals or objects. One process that could facilitate the anthropomorphization of nonhuman animals may be a self-other body-part matching mechanism wherein the body of the nonhuman animal is conceptually mapped to the human observer's representation of their body. The present study was designed to determine if specific features could facilitate body-part matching between the cartoon of a nonhuman animal and human observers. Participants responded to targets presented on the cartoon of a starfish. In No Structure conditions, dots and curved lines were distributed evenly within the starfish. In Face conditions, two dots and one curved line represented eyes and a mouth of a “face”. In Clothes conditions, dots and lines represented a shirt and pants. Body-part matching emerged when the image had a face or clothing, but did not emerge in No Structure conditions. These studies provide unique evidence that the anthropomorphization of a nonhuman cartoon may be facilitated by human-like internal features on the image.
The formation of protein clusters, or condensates, is frequently associated with specific types of membrane shaping that enhances stable connections and signal transmission between cells. Liquid–liquid phase separation has been emerged as an important mechanism that underlies the formation of protein condensates on plasma membranes. Phase-separated biomolecular condensates are discrete condensates composed of specific proteins that are formed on membranes. These condensates not only regulate a variety of signaling pathways and functional responses to external stimuli within cells but also provide physical support for membrane structures. Examples of these condensates include T cell signaling condensates, active zone condensates and postsynaptic densities in neuronal synapses, tight junctions between cells within layers of tissue, and nephrin condensates in the glomerular filtration barrier. In this chapter, we describe biological protein phase separation, how phase separation of membrane-associated proteins promotes membrane shaping and provide specific examples of protein condensates that contribute to local membrane structure.
Laminin 5, type 4 collagen, and α6β4 integrin contribute to the formation of hemidesmosomes in the epithelia of periodontal tissues, which is critical for the development and maintenance of the dentogingival junction. As it is not known whether TNF-α alters the composition of the epithelial pericellular matrix, human gingival epithelial cells were cultured in the presence or absence of TNF-α. Treatment with TNF-α accelerated epithelial cell migration and closure of in vitro wounds. These data indicate unexpectedly, that TNF-α promotes the formation of the pericellular matrix around epithelial cells and enhances adhesion of epithelial cells to the underlying matrix, properties which are important for cell migration and the integrity of the dentogingival junction.
The Lactobacillaceae are an intensively studied family of bacteria widely used in fermented food and probiotics, and many are native to the gut and vaginal microbiota of humans and other animals. Various studies have shown that specific Lactobacillaceae species produce metabolites that can inhibit the colonization of fungal and bacterial pathogens, but less is known about how Lactobacillaceae affect individual bacterial species in the endogenous animal microbiota. Here, we show that numerous Lactobacillaceae species inhibit the growth of the Lachnospiraceae family and the S24-7 group, two dominant clades of bacteria within the gut. We demonstrate that inhibitory activity is a property common to homofermentative Lactobacillaceae species, but not to species that use heterofermentative metabolism. We observe that homofermentative Lactobacillaceae species robustly acidify their environment, and that acidification alone is sufficient to inhibit growth of Lachnospiraceae and S24-7 growth, but not related species from the Clostridiales or Bacteroidales orders. This study represents one of the first in-depth explorations of the dynamic between Lactobacillaceae species and commensal intestinal bacteria, and contributes valuable insight toward deconvoluting their interactions within the gut microbial ecosystem.
No previous research has examined age and sex differences in balance outcomes in individuals with chronic obstructive pulmonary disease (COPD) at risk of falls. A secondary analysis of baseline data from an ongoing trial of fall prevention in COPD was conducted. Age and sex differences were analyzed for the Berg Balance scale (BBS), Balance Evaluation System Test (BEST test) and Activities-specific Balance Confidence Scale (ABC). Overall, 223 individuals with COPD were included. Females had higher balance impairments than males [BBS: mean (SD) = 47 (8) vs. 49 (6) points; BEST test: 73 (16) vs. 80 (16) points], and a lower confidence to perform functional activities [ABC = 66 (21) vs. 77 (19)]. Compared to a younger age (50-65 years) group, age >65 years was moderately associated with poor balance control [BBS (r = - 0.37), BEST test (r = - 0.33)] and weakly with the ABC scale (r = - 0.13). After controlling for the effect of balance risk factors, age, baseline dyspnea index (BDI), and the 6-min walk test (6-MWT) explained 38% of the variability in the BBS; age, sex, BDI, and 6-MWT explained 40% of the variability in the BEST test; And BDI and the 6-MWT explained 44% of the variability in the ABC scale. This study highlights age and sex differences in balance outcomes among individuals with COPD at risk of falls. Recognition of these differences has implications for pulmonary rehabilitation and fall prevention in COPD, particularly among females and older adults.
Dominant missense mutations in RanBP2/Nup358 cause Acute Necrotizing Encephalopathy (ANE), a pediatric disease where seemingly healthy individuals develop a cytokine storm that is restricted to the central nervous system in response to viral infection. Untreated, this condition leads to seizures, coma, long-term neurological damage and a high rate of mortality. The exact mechanism by which RanBP2 mutations contribute to the development of ANE remains elusive. In November 2021, a number of clinicians and basic scientists presented their work on this disease and on the interactions between RanBP2/Nup358, viral infections, the innate immune response and other cellular processes. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Successful translation of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors has proved to be troublesome, mainly due to the complex tumor microenvironment promoting T cell dysfunction and antigen heterogeneity. Mesothelin (MSLN) has emerged as an attractive target for CAR T cell therapy of several solid malignancies, including ovarian cancer. To improve clinical response rates with MSLN-CAR T cells, a better understanding of the mechanisms impacting CAR T cell functionality in vitro is crucial. Here, we demonstrated superior cytolytic capacity of CD28-costimulated MSLN-CAR T cells (M28z) relative to 4-1BB-costimulated MSLN-CAR T cells (MBBz). Furthermore, CD28-costimulated MSLN CAR T cells displayed enhanced cytolytic capacity against tumor spheroids with heterogeneous MSLN expression compared to MBBz CAR T cells. In this study, we identified CAR-mediated trogocytosis as a potential impeding factor for successful MSLN-CAR T cell therapy due to fratricide killing and contributing to tumor antigen heterogeneity. Moreover, we link antigen-dependent upregulation of LAG-3 with reduced CAR T cell functionality. Taken together, our study highlights the therapeutic potential and bottlenecks of MSLN-CAR T cells, providing a rationale for combinatorial treatment strategies.
Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to glycolipid antigens found in microbes in a CD1d-dependent manner. iNKT cells exert innate-like functions and produce copious amounts of cytokines, chemokines and cytotoxic molecules within only minutes of activation. As such, iNKT cells can fuel or dampen inflammation in a context-dependent manner. In addition, iNKT cells provide potent immunity against bacteria, viruses, parasites and fungi. Although microbiota-iNKT cell interactions are not well-characterized, mounting evidence suggests that microbiota colonization early in life impacts iNKT cell homeostasis and functions in disease. In this study, we showed that CD1d-/- and Vα14 Tg mice, which lack and have increased numbers of iNKT cells, respectively, had no significant alterations in gut microbiota composition compared to their littermate controls. Furthermore, specific iNKT cell activation by glycolipid antigens only resulted in a transient and minimal shift in microbiota composition when compared to the natural drift found in our colony. Our findings demonstrate that iNKT cells have little to no influence in regulating commensal bacteria at steady state.Abbreviations: iNKT: invariant Natural Killer T cell; αGC: α-galactosylceramide.
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45,665 members
Raphael Schneider
  • Department of Medicine
Sean Alexander Fitzgerald Peel
  • Dental Research Institute
Brett Q Ford
  • Department of Psychology
Farooq Naeem
  • Department of Psychiatry, Center for Addiction and Mental Health, Schizophrenia Program
27 King's College Circle, M5S 1A1, Toronto, ON, Canada
Head of institution
Meric Gertler
416 978 6457
416 978 6458