Waterloo Research

Permanent URI for this collectionhttps://uwspace.uwaterloo.ca/handle/10012/9972

This is the University of Waterloo Research collection.

Waterloo faculty, students, and staff can contact us or visit the UWSpace guide to learn more about depositing their research.

NOTE: This collection does not include graduate Theses & Dissertations or Major Research Projects.

Browse

Now showing 1 - 20 of 2714

Assessing ML classification algorithms and NLP techniques for depression detection: An experimental case study
(Public Library of Science (PLOS), 2025) Lorenzoni, Giuliano; Tavares, Cristina; Nascimento, Nathalia; Alencar, Paulo; Cowan, Donald
Context and background. Depression has affected millions of people worldwide and has become one of the most common mental disorders. Early mental disorder detection can reduce costs for public health agencies and prevent other major comorbidities. Additionally, the shortage of specialized personnel is very concerning since depression diagnosis is highly dependent on expert professionals and is time-consuming. Research problems. Recent research has evidenced that machine learning (ML) and natural language processing (NLP) tools and techniques have significantly benefited the diagnosis of depression. However, there are still several challenges in the assessment of depression detection approaches in which other conditions such as post-traumatic stress disorder (PTSD) are present. These challenges include assessing alternatives in terms of data cleaning and pre-processing techniques, feature selection, and appropriate ML classification algorithms. Purpose of the study. This paper tackles such an assessment based on a case study that compares different ML classifiers, specifically in terms of data cleaning and pre-processing, feature selection, parameter setting, and model choices. Methodology. The experimental case study is based on the Distress Analysis Interview Corpus - Wizard-of-Oz (DAIC-WOZ) dataset, which is designed to support the diagnosis of mental disorders such as depression, anxiety, and PTSD. Major findings. Besides the assessment of alternative techniques, we were able to build models with accuracy levels around 84% with Random Forest and XGBoost models, which is significantly higher than the results from the comparable literature which presented the level of accuracy of 72% from the SVM model. Conclusions. More comprehensive assessments of ML classification algorithms and NLP techniques for depression detection can advance the state of the art in terms of improved experimental settings and performance.
Targets and trade-offs: Designing environmental water transactions to navigate compounding competition on the San Saba River in Texas
(Public Library of Science (PLOS), 2025) Wight, Charles; Garmany, Kyle; Smith, Ryan; Garrick, Dustin; Richter, Brian
In river basins experiencing water scarcity, water demands for freshwater ecosystems and water users increasingly compete with one another. Environmental water transactions (EWT) offer a mechanism for resolving this competition via a voluntary agreement in which existing water users are paid to modify the time, place and/or volume of their water right to provide an environmental benefit. However, the disconnect between surface water and groundwater management creates barriers to implementation and scaling of EWTs. We study EWTs addressing water scarcity in Texas’s San Saba River, focusing on targeting the location and timing to fulfill conservation objectives. We integrate recent hydrological studies to identify trends in groundwater-surface water interaction, prioritizing stream reaches for intervention and considering both geologic and anthropogenic drivers of scarcity. We analyze water rights and well data to estimate consumptive water demands during the irrigation season. We quantify the volumetric contribution of different portfolios of water rights paired with different types of EWT to assess their contributions to flow targets, including costs and benefits associated with each portfolio. Results demonstrate that the effectiveness of EWTs relies on coordinated spatial and temporal targeting within the context of hydrogeological settings and water users. We provide cost estimates for implementing four types of EWTs ranging from one season to perpetuity ($32,040 and $404,722 respectively) that can provide 3 cubic feet per second (cfs) (0.085 cubic meters) to help meet subsistence flows in the height of irrigation season (June-Aug). These costs are contextualized within a broader water governance context that considers the benefits to producers and the environment and underscores the importance of future policy to integrate groundwater-surface water interaction.
Simulation study to evaluate when Plasmode simulation is superior to parametric simulation in comparing classification methods on high-dimensional data
(Public Library of Science (PLOS), 2025) Stolte, Marieka; Schreck, Nicholas; Slynko, Alla; Saadati, Maral; Benner, Axel; Rahnenfuhrer, Jorg; Bommert, Andrea
Simulation studies, especially neutral comparison studies, are crucial for evaluating and comparing statistical methods as they investigate whether methods work as intended and can guide an appropriate method choice. Typically, the term simulation refers to parametric simulation, i.e. computer experiments using pseudo-random numbers. For these, the full data-generating process (DGP) and outcome-generating model (OGM) are known within the simulation. However, the specification of realistic DGPs might be difficult in practice leading to oversimplified assumptions. The problem is more severe for higher-dimensional data as the number of parameters to specify typically increases with the number of variables in the data. Plasmode simulation, which is a combination of resampling covariates from a real-life dataset from the DGP of interest together with a specified OGM is often claimed to solve this problem since no explicit specification of the DGP is necessary. However, this claim is not well supported by empirical results. Here, parametric and Plasmode simulations are compared in the context of a method comparison study for binary classification methods. We focus on studies conducted with some specific data type or application in mind whose true, unknown data-generating mechanism is mimicked. The performance of Plasmode and parametric comparison studies for estimating classifier performance is compared as well as their ability to reproduce the true method ranking. The influence of misspecifications of the DGP on the results of parametric simulation and of misspecifications of the OGM on the results of parametric and Plasmode simulation are investigated. Moreover, different resampling strategies are compared for Plasmode comparison studies. The study finds that misspecifications of the DGP and OGM negatively influence the ability of the comparison studies to estimate the classification performances and method rankings. The best choice of the resampling strategy in Plasmode simulation depends on the concrete scenario.
Efficacy of a new nanoemulsion artificial tear in dry eye disease management: Study protocol for a prospective cohort study
(Public Library of Science (PLOS), 2025) Liao, Xulin; Guo, Biyue; Bian, Jingfang; Li, Peter H.; Tse, Jimmy S. H.; Ngo, William; Zhou, Lei; Lam, Thomas
Background Dry eye disease (DED) is a complex ocular disorder with a significant prevalence worldwide, especially in the Asian population. This study aimed to investigate changes in dry eye symptoms and signs following regular use of a new nanoemulsion eye drop, Systane COMPLETE Multi-Dose Preservative-Free (MDPF), in patients with mild to moderate DED in the Asian population. Methods and design This is a prospective cohort study (ClinicalTrials.gov identifier: NCT06188260) that aims to recruit approximately 40 patients from the Asian population suffering from mild to moderate DED. Mild to moderate DED is defined according to the Tear Film and Ocular Surface Society (TFOS) Dry Eye Workshop (DEWS) II diagnostic criteria, including an Ocular Surface Disease Index (OSDI) score between 13-32, and with at least one of the following positive signs: corneal staining, Non-Invasive Tear Breakup Time (NITBUT), or osmolarity. The proposed follow-up period is 3 months. Patients undergo three assessments: baseline before using the eye drops, and follow-up visits after 2 weeks and 3 months regular use of the eye drops (four times daily). The primary outcome is the change in the OSDI score at 2 weeks. Discussion The results examine the dry eye symptoms before and after using the new nanoemulsion eye drop, Systane COMPLETE MDPF, in a cohort of mild to moderate DED sufferers. The findings may provide new treatment options for dry eye sufferers with significant clinical implications.
Adrenocorticotropic Hormone Suppresses Gonadotropin-Stimulated Estradiol Release from Zebrafish Ovarian Follicles
(Public Library of Science (PLOS), 2009) Alsop, Derek; Ings, Jennifer S.; Vijayan, Mathilakath M.
While stress is known to impact reproductive performance, the pathways involved are not entirely understood. Corticosteroid effects on the functioning of the hypothalamus-pituitary-gonadal axis are thought to be a key aspect of stress-mediated reproductive dysfunction. A vital component of the stress response is the pituitary secretion of adrenocorticotropic hormone (ACTH), which binds to the melanocortin 2 receptor (MC2R) in the adrenal glands and activates cortisol biosynthesis. We recently reported MC2R mRNA abundance in fish gonads leading to the hypothesis that ACTH may be directly involved in gonadal steroid modulation. Using zebrafish (Danio rerio) ovarian follicles, we tested the hypothesis that acute ACTH stimulation modulates cortisol and estradiol (E2) secretion. ACTH neither affected cortisol nor unstimulated E2 release from ovarian follicles. However, ACTH suppressed human chorionic gonadotropin (hCG)-stimulated E2 secretion in a dose-related manner, with a maximum decrease of 62% observed at 1 I.U. ACTH mL−1. This effect of ACTH on E2 release was not observed in the presence of either 8-bromo-cAMP or forskolin, suggesting that the mechanism(s) involved in steroid attenuation was upstream of adenylyl cyclase activation. Overall, our results suggest that a stress-induced rise in plasma ACTH levels may initiate a rapid down-regulation of acute stimulated E2 biosynthesis in the zebrafish ovary, underscoring a novel physiological role for this pituitary peptide in modulating reproductive activity.
Tension at the surface: Which phase is more important, liquid or vapor?
(Public Library of Science (PLOS), 2009) Prpich, Andrew M.; Sheng, Yuebiao; Wang, Wei; Biswas, M. Elias; Chen, P.
Tension at the surface is a most fundamental physicochemical property of a liquid surface. The concept of surface tension has widespread implications in numerous natural, engineering and biomedical processes. Research to date has been largely focused on the liquid side; little attention has been paid to the vapor—the other side of the surface, despite over 100 years of study. However, the question remains as to whether the vapor plays any role, and to what extent it affects the surface tension of the liquid. Here we show a systematic study of the effect of vapor on the surface tension and in particular, a surprising observation that the vapor, not the liquid, plays a dominant role in determining the surface tension of a range of common volatile organic solutions. This is in stark contrast to results of common surfactants where the concentration in the liquid plays the major role. We further confirmed our results with a modified adsorption isotherm and molecular dynamics simulations, where highly structured, hydrogen bonded networks, and in particular a solute depletion layer just beneath the Gibbs dividing surface, were revealed.
Estimating the Stochastic Bifurcation Structure of Cellular Networks
(Public Library of Science (PLOS), 2010) Song, Carl; Phenix, Hilary; Abedi, Vida; Scott, Matthew; Ingalls, Brian P.; Kaern, Mads; Perkins, Theodore J.
High throughput measurement of gene expression at single-cell resolution, combined with systematic perturbation of environmental or cellular variables, provides information that can be used to generate novel insight into the properties of gene regulatory networks by linking cellular responses to external parameters. In dynamical systems theory, this information is the subject of bifurcation analysis, which establishes how system-level behaviour changes as a function of parameter values within a given deterministic mathematical model. Since cellular networks are inherently noisy, we generalize the traditional bifurcation diagram of deterministic systems theory to stochastic dynamical systems. We demonstrate how statistical methods for density estimation, in particular, mixture density and conditional mixture density estimators, can be employed to establish empirical bifurcation diagrams describing the bistable genetic switch network controlling galactose utilization in yeast Saccharomyces cerevisiae. These approaches allow us to make novel qualitative and quantitative observations about the switching behavior of the galactose network, and provide a framework that might be useful to extract information needed for the development of quantitative network models.
Integrin α5β1 Function Is Regulated by XGIPC/kermit2 Mediated Endocytosis during Xenopus laevis Gastrulation
(Public Library of Science (PLOS), 2010) Spicer, Erin; Suckert, Catherine; Al-Attar, Hyder; Marsden, Mungo
During Xenopus gastrulation α5β1 integrin function is modulated in a temporally and spatially restricted manner, however, the regulatory mechanisms behind this regulation remain uncharacterized. Here we report that XGIPC/kermit2 binds to the cytoplasmic domain of the α5 subunit and regulates the activity of α5β1 integrin. The interaction of kermit2 with α5β1 is essential for fibronectin (FN) matrix assembly during the early stages of gastrulation. We further demonstrate that kermit2 regulates α5β1 integrin endocytosis downstream of activin signaling. Inhibition of kermit2 function impairs cell migration but not adhesion to FN substrates indicating that integrin recycling is essential for mesoderm cell migration. Furthermore, we find that the α5β1 integrin is colocalized with kermit2 and Rab 21 in embryonic and XTC cells. These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the α5β1 integrin through receptor endocytosis.
Bisphenol A in Oocytes Leads to Growth Suppression and Altered Stress Performance in Juvenile Rainbow Trout
(Public Library of Science (PLOS), 2010) Aluru, Neelakanteswar; Leatherland, John F.; Vijayan, Mathilakath M.
Background Bisphenol A (BPA), used in the manufacture of plastics, is ubiquitously distributed in the aquatic environment. However, the effect of maternal transfer of these xenobiotics on embryonic development and growth is poorly understood in fish. We tested the hypothesis that BPA in eggs, mimicking maternal transfer, impact development, growth and stress performance in juveniles of rainbow trout (Oncorhynchus mykiss). Methodology/Principal Findings Trout oocytes were exposed to 0, 30 and 100 µg.mL−1 BPA for 3 h in ovarian fluid, followed by fertilization. The embryos were maintained in clean water and sampled temporally over 156-days post-fertilization (dpf), and juveniles were sampled at 400-dpf. The egg BPA levels declined steadily after exposure and were undetectable after 21- dpf. Oocyte exposure to BPA led to a delay in hatching and yolk absorption and a consistently lower body mass over 152-dpf. The growth impairment, especially in the high BPA group, correlated with higher growth hormone (GH) content and lower GH receptors gene expression. Also, mRNA abundances of insulin-like growth factors (IGF-1 and IGF-2) and their receptors were suppressed in the BPA treated groups. The juvenile fish grown from the BPA-enriched eggs had lower body mass and showed perturbations in plasma cortisol and glucose response to an acute stressor. Conclusion BPA accumulation in eggs, prior to fertilization, leads to hatching delays, growth suppression and altered stress response in juvenile trout. The somatotropic axis appears to be a key target for BPA impact during early embryogenesis, leading to long term growth and stress performance defects in fish.
Quantitative Epistasis Analysis and Pathway Inference from Genetic Interaction Data
(Public Library of Science (PLOS), 2011) Phenix, Hilary; Morin, Katy; Batenchuk, Cory; Parker, Jacob; Abedi, Vida; Yang, Liu; Tepliakova, Lioudmila; Perkins, Theodore J.; Kaern, Mads
Inferring regulatory and metabolic network models from quantitative genetic interaction data remains a major challenge in systems biology. Here, we present a novel quantitative model for interpreting epistasis within pathways responding to an external signal. The model provides the basis of an experimental method to determine the architecture of such pathways, and establishes a new set of rules to infer the order of genes within them. The method also allows the extraction of quantitative parameters enabling a new level of information to be added to genetic network models. It is applicable to any system where the impact of combinatorial loss-of-function mutations can be quantified with sufficient accuracy. We test the method by conducting a systematic analysis of a thoroughly characterized eukaryotic gene network, the galactose utilization pathway in Saccharomyces cerevisiae. For this purpose, we quantify the effects of single and double gene deletions on two phenotypic traits, fitness and reporter gene expression. We show that applying our method to fitness traits reveals the order of metabolic enzymes and the effects of accumulating metabolic intermediates. Conversely, the analysis of expression traits reveals the order of transcriptional regulatory genes, secondary regulatory signals and their relative strength. Strikingly, when the analyses of the two traits are combined, the method correctly infers ∼80% of the known relationships without any false positives.
Area 5 influences excitability within the primary motor cortex in humans
(Public Library of Science (PLOS), 2011) Premji, Azra; Rai, Navjot; Nelson, Aimee
In non-human primates, Brodmann's area 5 (BA 5) has direct connectivity with primary motor cortex (M1), is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS), intermittent (iTBS), and sham theta-burst stimulation (sham TBS) over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations.
Numerical modeling of fluid flow in solid tumors
(Public Library of Science (PLOS), 2011) Soltani, M.; Chen, P.
A mathematical model of interstitial fluid flow is developed, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for a predefined tumor geometry. The interstitial fluid pressure and velocity are calculated using a numerical method, element based finite volume. Simulations of interstitial fluid transport in a homogeneous solid tumor demonstrate that, in a uniformly perfused tumor, i.e., one with no necrotic region, because of the interstitial pressure distribution, the distribution of drug particles is non-uniform. Pressure distribution for different values of necrotic radii is examined and two new parameters, the critical tumor radius and critical necrotic radius, are defined. Simulation results show that: 1) tumor radii have a critical size. Below this size, the maximum interstitial fluid pressure is less than what is generally considered to be effective pressure (a parameter determined by vascular pressure, plasma osmotic pressure, and interstitial osmotic pressure). Above this size, the maximum interstitial fluid pressure is equal to effective pressure. As a consequence, drugs transport to the center of smaller tumors is much easier than transport to the center of a tumor whose radius is greater than the critical tumor radius; 2) there is a critical necrotic radius, below which the interstitial fluid pressure at the tumor center is at its maximum value. If the tumor radius is greater than the critical tumor radius, this maximum pressure is equal to effective pressure. Above this critical necrotic radius, the interstitial fluid pressure at the tumor center is below effective pressure. In specific ranges of these critical sizes, drug amount and therefore therapeutic effects are higher because the opposing force, interstitial fluid pressure, is low in these ranges.
Estimation of mental effort in learning visual search by measuring pupil response
(Public Library of Science (PLOS), 2011) Takeuchi, Tatsuto; Puntous, Theodore; Tuladhar, Anup; Yoshimoto, Sanae; Shirama, Aya
Perceptual learning refers to the improvement of perceptual sensitivity and performance with training. In this study, we examined whether learning is accompanied by a release from mental effort on the task, leading to automatization of the learned task. For this purpose, we had subjects conduct a visual search for a target, defined by a combination of orientation and spatial frequency, while we monitored their pupil size. It is well known that pupil size reflects the strength of mental effort invested in a task. We found that pupil size increased rapidly as the learning proceeded in the early phase of training and decreased at the later phase to a level half of its maximum value. This result does not support the simple automatization hypothesis. Instead, it suggests that the mental effort and behavioral performance reflect different aspects of perceptual learning. Further, mental effort would be continued to be invested to maintain good performance at a later stage of training.
Aquarium nitrification revisited: Thaumarchaeota are the dominant ammonia oxidizers in freshwater aquarium biolfilters
(Public Library of Science (PLOS), 2011) Sauder, Laura A.; Engel, Katja; Stearns, Jennifer C.; Masella, Andre P.; Pawliszyn, Richard; Neufeld, Josh D.
Ammonia-oxidizing archaea (AOA) outnumber ammonia-oxidizing bacteria (AOB) in many terrestrial and aquatic environments. Although nitrification is the primary function of aquarium biofilters, very few studies have investigated the microorganisms responsible for this process in aquaria. This study used quantitative real-time PCR (qPCR) to quantify the ammonia monooxygenase (amoA) and 16S rRNA genes of Bacteria and Thaumarchaeota in freshwater aquarium biofilters, in addition to assessing the diversity of AOA amoA genes by denaturing gradient gel electrophoresis (DGGE) and clone libraries. AOA were numerically dominant in 23 of 27 freshwater biofilters, and in 12 of these biofilters AOA contributed all detectable amoA genes. Eight saltwater aquaria and two commercial aquarium nitrifier supplements were included for comparison. Both thaumarchaeal and bacterial amoA genes were detected in all saltwater samples, with AOA genes outnumbering AOB genes in five of eight biofilters. Bacterial amoA genes were abundant in both supplements, but thaumarchaeal amoA and 16S rRNA genes could not be detected. For freshwater aquaria, the proportion of amoA genes from AOA relative to AOB was inversely correlated with ammonium concentration. DGGE of AOA amoA genes revealed variable diversity across samples, with nonmetric multidimensional scaling (NMDS) indicating separation of freshwater and saltwater fingerprints. Composite clone libraries of AOA amoA genes revealed distinct freshwater and saltwater clusters, as well as mixed clusters containing both freshwater and saltwater amoA gene sequences. These results reveal insight into commonplace residential biofilters and suggest that aquarium biofilters may represent valuable biofilm microcosms for future studies of AOA ecology.
Weekly iron-folic acid supplementation with regular deworming is cost-effective in preventing anaemia in women of reproductive age in Vietnam
(Public Library of Science (PLOS), 2011) Casey, Gerard J.; Sartori, Davide; Horton, Susan E.; Phuc, Tran Q.; Phu, Luong B.; Thach, Dang T.; Dai, Tran C.; Fattore, Giovanni; Montresor, Antario; Biggs, Beverly-A.
Background To estimate the cost and cost-effectiveness of a project administering de-worming and weekly iron-folic acid supplementation to control anaemia in women of reproductive age in Yen Bai province, Vietnam. Methods and Findings Cost effectiveness was evaluated using data on programmatic costs based on two surveys in 2006 and 2009 and impact on anaemia and iron status collected in 2006, 2007, and 2008. Data on initial costs for training and educational materials were obtained from the records of the National Institute of Malariology, Parasitology and Entomology and the Yen Bai Malaria Control Program. Structured questionnaires for health workers at district, commune and village level were used to collect ongoing distribution and monitoring costs, and for participants to collect transport and loss of earnings costs. The cost per woman treated (defined as consuming at least 75% of the recommended intake) was USD0.76 per annum. This estimate includes financial costs (for supplies, training), and costs of health care workers' time. Prevalence of anaemia fell from 38% at baseline, to 20% after 12 months. Thus, the cost-effectiveness of the project is assessed at USD 4.24 per anaemia case prevented per year. Based on estimated productivity gains for adult women, the benefit:cost ratio is 6.7∶1. Cost of the supplements and anthelminthics was 47% of the total, while costs of training, monitoring, and health workers' time accounted for 53%. Conclusion The study shows that weekly iron-folic acid supplementation and regular de-worming is a low-cost and cost-effective intervention and would be appropriate for population-based introduction in settings with a high prevalence of anaemia and iron deficiency and low malaria infection rates.
DRhoGEF2 regulates cellular tension and cell pulsations in the Amniosera during Drosophila dorsal closure
(Public Library of Science (PLOS), 2011) Azevedo, Dulce; Antunes, Marco; Prag, Soren; Ma, Xiaoyan; Hacker, Udo; Brodland, G. Wayne; Hutson, M. Shane; Solon, Jerome; Jacinto, Antonio
Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction.
Fine-tuning and the stability of recurrent neural networks
(Public Library of Science (PLOS), 2011) MacNeil, David; Eliasmith, Chris
A central criticism of standard theoretical approaches to constructing stable, recurrent model networks is that the synaptic connection weights need to be finely-tuned. This criticism is severe because proposed rules for learning these weights have been shown to have various limitations to their biological plausibility. Hence it is unlikely that such rules are used to continuously fine-tune the network in vivo. We describe a learning rule that is able to tune synaptic weights in a biologically plausible manner. We demonstrate and test this rule in the context of the oculomotor integrator, showing that only known neural signals are needed to tune the weights. We demonstrate that the rule appropriately accounts for a wide variety of experimental results, and is robust under several kinds of perturbation. Furthermore, we show that the rule is able to achieve stability as good as or better than that provided by the linearly optimal weights often used in recurrent models of the integrator. Finally, we discuss how this rule can be generalized to tune a wide variety of recurrent attractor networks, such as those found in head direction and path integration systems, suggesting that it may be used to tune a wide variety of stable neural systems.
Effect of surfaces on amyloid fibril formation
(Public Library of Science (PLOS), 2011) Moores, Bradley; Drolle, Elizabeth; Attwood, Simon J.; Simons, Janet; Leonenko, Zoya
Using atomic force microscopy (AFM) we investigated the interaction of amyloid beta (Aβ) (1–42) peptide with chemically modified surfaces in order to better understand the mechanism of amyloid toxicity, which involves interaction of amyloid with cell membrane surfaces. We compared the structure and density of Aβ fibrils on positively and negatively charged as well as hydrophobic chemically-modified surfaces at physiologically relevant conditions. We report that due to the complex distribution of charge and hydrophobicity amyloid oligomers bind to all types of surfaces investigated (CH3, COOH, and NH2) although the charge and hydrophobicity of surfaces affected the structure and size of amyloid deposits as well as surface coverage. Hydrophobic surfaces promote formation of spherical amorphous clusters, while charged surfaces promote protofibril formation. We used the nonlinear Poisson-Boltzmann equation (PBE) approach to analyze the electrostatic interactions of amyloid monomers and oligomers with modified surfaces to complement our AFM data.
Microsecond molecular dynamics simulations of intrinsically didsordered proteins involved in the oxidative stress response
(Public Library of Science (PLOS), 2011) Cino, Elio A.; Wong-ekkabut, Jirasak; Karttunen, Mikko; Choy, Wing-Yiu
Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα) and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2), with a common binding partner, Kelch-like ECH-associated protein 1(Keap1), are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5–1.0 microsecond atomistic molecular dynamics (MD) simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs) and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.
Canadian Construction Automation and Robotics Roadmap
(University of Waterloo, 2025-05-29) Haas, Carl; Olumo, Adama; Hwang, Joon Ha; Docking, Angie; Shahi, Arash; Kim, Joyce; Katsimpalis, Emmanouil
Automation and robotics play a key role in construction productivity gains. A construction automation and robotics R&D roadmap to achieve such gains in Canada is presented in this report. Developed through workshops, practice and literature reviews, analysis, and synthesis, it includes an overall framework for how key Canadian stakeholders may participate in a technology pipeline that creates construction productivity gains through application of automation and robotics. Key knowledge and implementation gaps from the perspective of the construction industry are identified, as well as impediments to implementation of automation and robotics in construction. Suggestions are made for means by which such impediments can be overcome, and recommendations are made for implementation of a construction automation and robotics R&D program that will expedite deployment of solutions at scale.

Browse

Recent Submissions