Projets novateurs réalisés

Interaction between cannabinoid drugs and sodium channels in diabetes/high glucose induced oxidative stress, neuroinflammation, and neurotoxicity – Year two

Diabetes mellitus, a common metabolic disorder, exhibits neuropathic complications that can eventually lead to disabling pain (Todorovic 2015). This is attributed to hyperglycemia/high glucose resulting in neuronal hyperexcitability (Todorovic 2015). Importantly, diabetes-evoked neuronal hyperexcitability and neurotoxicity can be caused by alterations in voltage-gated sodium channel (VGSC) expression (Hong, Morrow et al. 2004), resulting in changes in the sodium currents lowering the action potential threshold (Hong, Morrow et al. 2004, Chen, Wang et al. 2018). Interestingly, cannabinoids exert antinociceptive properties. In addition, both cannabinoid receptors, CB-1 and CB-2, are highly expressed in central and peripheral nervous systems, suggesting a fundamental role in nociception (Agarwal, Pacher et al. 2007, Rahn and Hohmann 2009). Also, estrogen (E2) loses its neuroprotective effect, or worsens neuronal injury in diabetic animals (Santizo, Xu et al. 2002). Thus, the current study aims to investigate the role of VGSC in high glucose-induced neurotoxicity, and whether high glucose modulation of VGSC can be altered using cannabinoids. Also, this study will investigate sex-determined modulation of cannabinoid/VGSC interaction in high glucose elicited neurotoxicity. Noteworthy, our results may identify novel molecular targets for alleviating neuropathic pain and solve the sex-specific exacerbation of neurological dysfunction elicited by diabetes.

Méthodologie de conception, vérification, et test des systèmes embarquéstolérants aux radiations

STAGIAIRE1 (PhD1, ISR) Génération et propagation des requis de conception vers le

sous-système électronique embarqué.

Les objectifs spécifiques du projet de l’étudiant PhD1 (tâches 1.1 et 1.2 du projet global)

sont : 1) l’élaboration, la mise en oeuvre et la validation d’une stratégie permettant de

déterminer la robustesse inhérente des autres éléments du système global, afin de définir les

spécifications de fiabilité au niveau du sous-système embarqué, et 2) l’élaboration, la mise en

oeuvre et la validation d’une stratégie permettant de déterminer les requis de

fiabilité/robustesse des diverses parties de l’application embarquée au niveau sous-système,

à partir de ceux identifiés au niveau système. Ces requis de robustesse seront par la suite

utilisés pour guider le partitionnement et le choix des circuits (rad-hard versus non rad-hard)..

Le partenaire industriel, ISR, va fournir des exemples (modèles) de sous-systèmes. Ces

modèles seront utilisés comme cas d’étude par l’étudiant pendant son stage. L’étudiant aura

également accès aux concepteurs de ces modèles. En contrepartie, la compagnie va…………………………………….

Interaction between cannabinoid drugs and sodium channels in diabetes/high glucose induced oxidative stress, neuroinflammation, and neurotoxicity

Diabetes mellitus, a common metabolic disorder, exhibits neuropathic complications that can eventually lead to disabling pain (Todorovic 2015). This is attributed to hyperglycemia/high glucose resulting in neuronal hyperexcitability (Todorovic 2015). Importantly, diabetes-evoked neuronal hyperexcitability and neurotoxicity can be caused by alterations in voltage-gated sodium channel (VGSC) expression (Hong, Morrow et al. 2004), resulting in changes in the sodium currents lowering the action potential threshold (Hong, Morrow et al. 2004, Chen, Wang et al. 2018). Interestingly, cannabinoids exert antinociceptive properties. In addition, both cannabinoid receptors, CB-1 and CB-2, are highly expressed in central and peripheral nervous systems, suggesting a fundamental role in nociception (Agarwal, Pacher et al. 2007, Rahn and Hohmann 2009). Also, estrogen (E2) loses its neuroprotective effect, or worsens neuronal injury in diabetic animals (Santizo, Xu et al. 2002). Thus, the current study aims to investigate the role of VGSC in high glucose-induced neurotoxicity, and whether high glucose modulation of VGSC can be altered using cannabinoids. Also, this study will investigate sex-determined modulation of cannabinoid/VGSC interaction in high glucose elicited neurotoxicity. Noteworthy, our results may identify novel molecular targets for alleviating neuropathic pain and solve the sex-specific exacerbation of neurological dysfunction elicited by diabetes.

Silicon Quantum Dot Trace Explosive Sensor – Year two

The rapid detection of high energy materials (i.e., explosives) and chemical, biological and radioactive (CBR) agents have received substantial attention because of its obvious importance to security and forensics. Applied Quantum Materials Inc. (AQM) is developing a straightforward luminescent quantum dot paper- and/or cloth-based detection system that shows instantaneous optical detection of nitro-based explosives in solution and solid phases at nanogram levels by monitoring the luminescence quenching after being exposed to explosive residues.

The issue at hand is the current quantum dot (QD) sensor cannot distinguish between different nitro-based explosive groups (i.e., nitroaromatics, nitramines, and nitrate esters). Furthermore, the current technology cannot detect explosive inorganic salts (i.e., nitrate- and chlorate-based). The Research Intern will be responsible for working with AQM and its partners to develop and test the capabilities of the AQM QD sensor for its selectivity and the initial basic research for the development of new sensors for the detection of inorganic salts and chemical warfare agents. The sensors will be tested for their applications for first responders in the field, border control, and aviation security.

Silicon Quantum Dot Trace Explosive Sensor

The rapid detection of high energy materials (i.e., explosives) and chemical, biological and radioactive (CBR) agents have received substantial attention because of its obvious importance to security and forensics. Applied Quantum Materials Inc. (AQM) is developing a straightforward luminescent quantum dot paper- and/or cloth-based detection system that shows instantaneous optical detection of nitro-based explosives in solution and solid phases at nanogram levels by monitoring the luminescence quenching after being exposed to explosive residues.

The issue at hand is the current quantum dot (QD) sensor cannot distinguish between different nitro-based explosive groups (i.e., nitroaromatics, nitramines, and nitrate esters). Furthermore, the current technology cannot detect explosive inorganic salts (i.e., nitrate- and chlorate-based). The Research Intern will be responsible for working with AQM and its partners to develop and test the capabilities of the AQM QD sensor for its selectivity and the initial basic research for the development of new sensors for the detection of inorganic salts and chemical warfare agents. The sensors will be tested for their applications for first responders in the field, border control, and aviation security.

Enabling next generation cardiac therapeutics with genetic engineering and novel in vivo models for cardiomyocyte transplantation – Year two

The development of cellular therapeutics is acutely dependent on the ability to evaluate the functional characteristics of the cells in predictive animal models. This forms the basis of key pre-clinical data packages that are key for regulatory submissions preceding human clinical trials. The development of appropriate model systems, the execution of the surgical techniques to deliver cells to the target tissue, and the techniques to functionally analyze these cells in situ are technically challenging. Michael Laflamme’s laboratory is focussed on the development of protocols for making and testing human stem cell derived cardiomyocytes in animal models and is the world leader in this field. BlueRock Therapeutics (BRT) is actively developing a clinical and commercial pipeline of cell therapies for cardiac indications. This proposal bridges development work being done in the Laflamme lab and at BRT. The data that will be generated in the project will be instrumental in shaping BRT’s development pipeline. Further, the project will provide Wahiba, the proposed trainee, with an opportunity to work with BRT staff to propose a business case and implementation plan for the internalization of this highly specialized skill set within the company.

Enabling next generation cardiac therapeutics with genetic engineering and novel in vivo models for cardiomyocyte transplantation

The development of cellular therapeutics is acutely dependent on the ability to evaluate the functional characteristics of the cells in predictive animal models. This forms the basis of key pre-clinical data packages that are key for regulatory submissions preceding human clinical trials. The development of appropriate model systems, the execution of the surgical techniques to deliver cells to the target tissue, and the techniques to functionally analyze these cells in situ are technically challenging. Michael Laflamme’s laboratory is focussed on the development of protocols for making and testing human stem cell derived cardiomyocytes in animal models and is the world leader in this field. BlueRock Therapeutics (BRT) is actively developing a clinical and commercial pipeline of cell therapies for cardiac indications. This proposal bridges development work being done in the Laflamme lab and at BRT. The data that will be generated in the project will be instrumental in shaping BRT’s development pipeline. Further, the project will provide Wahiba, the proposed trainee, with an opportunity to work with BRT staff to propose a business case and implementation plan for the internalization of this highly specialized skill set within the company.

Modeling and control of CPP’s proprietary Mighty Dredge & Bypass Pump Technologies

Canada Pump & Power (CPP) is an Alberta specialized industrial marine company. CPP has a novel proprietary dredge propulsion method based on a set of winch-driven cables: the patented Autonomous Mighty Dredge. Control strategies to date have delivered adequate performance in some operating conditions; the goal is to have the dredge capable of performing to a slurry rate specification under automatic control in a wide range of operating conditions (variable deposits, density, obstacles). CPP is also developing a new, proprietary Autonomous Submersible Bypass Pump, which automates submersible operations, is managed by a computer program and interface, and can work with the dredge or on its own. CPP is looking for university-based research to examine the controllability problem, identify candidate control schemes, including model-based control and control methods based on machine learning using data from current dredging and pumping operations. Issues of Observability and Controllability will be addressed through a laboratory-based program of developing a scaled-down dredge system with controllable dredging conditions for data collection and control verification studies, with the intent to test the likely control techniques to an industrial prototype automated dredge at CPP’s Ardrossan facility.

MIM Plasmonic Bowtie Structures for Infrared Spectroscopy

Infrared (IR) spectroscopy is a diverse, powerful and nondestructive sensing technique amenable to a wide variety of applications. The sensitivity of IR measurements can be greatly improved by local electromagnetic field enhancements provided by nanoscale metallic structures. We propose a novel platform for enhanced IR spectroscopy, consisting of a bowtie structure composed of a nanoscale metal-dielectric grating. This device will achieve unprecedented levels of field enhancement due to the combined effects of the bowtie structure and MIM grating, allowing for highly sensitive measurements to be performed. In addition, the completed bowtie devices will be incorporated into a microfluidic channel. This channel will allow solutions of interest to flow directly over the region of maximum field enhancement, facilitating the easy execution of various measurements. Using this device, we intend to demonstrate the detection of ultra-low concentrations of various molecules, with potential applications in many fields.

Biocontrol potential of entomopathogenic nematodes (EPNs) against selected key insect pests of canola, cereal and high value crops in Alberta.

Crop losses and the economic impact caused by canola insect pests is substantial, depending on outbreak conditions. With the predicted de-registration of two key insecticides, canola producers are potential subject to greater economic losses. Entomopathogenic nematodes (EPNs), also known as predatory nematodes, are commercially available biocontrol agents for the management of insect pests. Although below-ground insect stages are more susceptible to EPNs, recent advancement in application technology has improved their biocontrol efficiency against the foliar insect pests. In this project we propose to explore EPN use against foliar insect pests including flea beetles, diamond back moth, lygus, and below ground pest wireworms. Laboratory experiments will evaluate five different commercially available EPN species, at different rates required to kill the insect pests. Positive findings will direct future investigations under field trials with the long term goal of providing a sustainable insect pest management approach for Western Canadian growers.

Processus de retro-ingénierie par manipulation de nuages de points

Ce projet s’inscrivant dans le domaine de l‘ingénierie de visualisation 3D a pour principale objectif de permettre la manipulation de différents types de formats de CAD (Computer Aided Design). Actuellement, les manipulations de formats tel que les nuages de points ou les éléments maillés se font de manière séparée, empêchant le plein potentiel d’un modèle hybride. Un processus permettant l’utilisation non-trivial des données issues d’un nuage de points (grande précision géométrique) et d’éléments surfaciques (rendu visuel fidèle à la réalité et de haute qualité) permettrait la mise en place d’opération de retro-ingénierie (extraction d’information géométrique précise) directement dans un modèle de visualisation 3D. De ce fait, le fossé entre les logiciels de modélisation et simulation 3D et les logiciels de visualisation 3D est supprimé. TO BE CONT’D

Characterization of guided wave propagation in aircraft structures

Structural health monitoring (SHM) is a major area of interest for the aerospace community,

especially considering aging aircraft where the growing maintenance costs, estimated to

$10,4 billion worldwide annually, can reduce their economic life. The long-term goal of the

industry is to deploy SHM systems which will 1) meet the in-service inspection requirements

with sensors permanently installed on the structure and 2) provide operational and economic

benefits compared to the baseline inspection methods. Strategies using guided wave

propagation have been proposed for embedded monitoring of airframe structures. However,

wave propagation and interaction with defects in complex structures is addressed in the

literature only for specific and limited number of components and types of defects. For

example, interaction with cracks in metallic joints and debonding in composite joints has been

investigated to some extent. The objective of this knowledge-gap based research is to

provide the industry with an extended knowledge base for a variety of basic aircraft

structures, standards, from which the guided…….