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BCIT Citations Collection

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Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells
Aged garlic extract (AGE) is widely used as a dietary supplement, and is claimed to promote human health through anti-oxidant/anti-inflammatory activities with hypolipidemic, antiplatelet and neuroprotective effects. Prior studies of AGE have mainly focused on its organosulfur compounds, with little attention paid to its carbohydrate derivatives, such as N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg). The goal of this study is to investigate actions of AGE and FruArg on antioxidative and neuroinflammatory responses in lipopolysaccharide (LPS)-activated murine BV-2 microglial cells using a proteomic approach. Our data show that both AGE and FruArg can significantly inhibit LPS-induced nitric oxide (NO) production in BV-2 cells. Quantitative proteomic analysis by combining two dimensional differential in-gel electrophoresis (2D-DIGE) with mass spectrometry revealed that expressions of 26 proteins were significantly altered upon LPS exposure, while levels of 20 and 21 proteins exhibited significant changes in response to AGE and FruArg treatments, respectively, in LPS-stimulated BV-2 cells. Notably, approximate 78% of the proteins responding to AGE and FruArg treatments are in common, suggesting that FruArg is a major active component of AGE. MULTICOM-PDCN and Ingenuity Pathway Analyses indicate that the proteins differentially affected by treatment with AGE and FruArg are involved in inflammatory responses and the Nrf2-mediated oxidative stress response. Collectively, these results suggest that AGE and FruArg attenuate neuroinflammatory responses and promote resilience in LPS-activated BV-2 cells by suppressing NO production and by regulating expression of multiple protein targets associated with oxidative stress., Peer-reviewed article, Published. Received: May 16, 2014; Accepted: October 24, 2014; Published: November 24, 2014.
Protracted myelin clearance hinders central primary afferent regeneration following dorsal rhizotomy and delayed neurotrophin-3 treatment
Regeneration within or into the CNS is thwarted by glial inhibition at the site of a spinal cord injury and at the dorsal root entry zone (DREZ), respectively. At the DREZ, injured axons and their distal targets are separated by degenerating myelin and an astrocytic glia limitans. The different glial barriers to regeneration following dorsal rhizotomy are temporally and spatially distinct. The more peripheral astrocytic barrier develops first, and is surmountable by neurotrophin-3 (NT-3) treatment; the more central myelin-derived barrier, which prevents dorsal horn re-innervation by NT-3-treated axons, becomes significant only after the onset of myelin degeneration. Here we test the hypothesis that in the presence of NT-3, axonal regeneration is hindered by myelin degeneration products. To do so, we used the Long Evans Shaker (LES) rat, in which oligodendrocytes do not make CNS myelin, but do produce myelin-derived inhibitory proteins. We show that delaying NT-3 treatment for 1 week in normal (LE) rats, while allowing axonal penetration of the glia limitans and growth within degenerating myelin, results in misdirected regeneration with axons curling around presumptive degenerating myelin ovoids within the CNS compartment of the dorsal root. In contrast, delaying NT-3 treatment in LES rats resulted in straighter, centrally-directed regenerating axons. These results indicate that regeneration may be best optimized through a combination of neurotrophin treatment plus complete clearance of myelin debris., Peer-reviewed article, Published. Received 3 June 2006, Revised 8 September 2006, Accepted 8 September 2006, Available online 22 November 2006.
Purification and characterization of a selective growth regulator for human myelopoietic progenitor cells
A monoclonal antibody, named CAMAL-1, was raised previously in our laboratory to a common antigen of acute myeloid leukemia (CAMAL), and was shown to be highly specific in its recognition of cells from patients with acute (AML) or chronic (CML) myelogenous leukemia. CAMAL was also reported to be prognostic of disease, in that patients whose numbers of CAMAL-1 reactive cells were high, or rose over time, had poorer prognoses and shorter survival times than patients whose CAMAL values were low or decreased. This correlation between CAMAL and disease prognosis led to the discovery that CAMAL-1immunoaffinity-purified leukemic cellular lysates contained a selective growth inhibitory activity for normal myeloid progenitor cells, since the growth of CML progenitors was not inhibited. The work described in this thesis focused primarily on the purification and characterization of the myelopoietic activity present in the CAMAL preparations, and its relationship to the leukemic marker (CAMAL). Initial purifications involved CAMAL-1immunoaffinity chromatography of leukemic cellular lysates, followed by FPLC molecular size fractionation and/or preparative SDS-PAGE. The myelopoietic activity was located within a30-35 kDa molecular weight fraction (P30), and the P30 fraction was consistently found to be selective in its inhibition of normal myeloid progenitors, since the growth of CML progenitors was not inhibited but was, in fact, stimulated. Antibodies were raised to P30 and used in the subsequent purification and characterization of the myelopoietic activity. Amino acid sequence analysis of the N-terminus and P30 tryptic peptides strongly suggested that P30 belonged to the serine protease family of enzymes, and the results obtained from protease assays indicated thatP30 preparations did possess enzyme activity. Prior to the completion of P30 molecular cloning experiments, however, the cDNA sequence for azurocidin/CAP37 was reported, and its predicted amino acid sequence was found to be identical to those obtained from the P30 protein samples. Azurocidin is a proteolytically inactive serine protease homologue, normally present in neutrophilic granules. Purifiedazurocidin did not possess inhibitory activity in normal progenitor cell assays; therefore, in order to isolate the biologic activity from azurocidin and other potentially contaminating proteins, P30 preparations were fractionated by reverse phase HPLC. The rpHPLC profiles were found to be similar to those reported for neutrophilic granules; however, the myelopoietica ctivity was obtained in a single rpHPLC fraction that aligned with the front portion of the azurocidin protein peak. Two dimensional isoelectric focusing/SDS-PAGE analysis of the biologically active rpHPLC fraction confirmed that it contained azurocidin, and no additional protein species were detected. Only the earlier eluting azurocidin rpHPLC fraction mediated the myelopoietic activity, and this fraction was also enriched in the higher molecular weight isoforms of azurocidin. Therefore, it appeared that a variably glycosylated isoform of azurocidin was mediating the biologic effects on myeloid progenitor cells, and because azurocidin obtained from normal neutrophils did not possess the myelopoietic activity, we speculate that the bioactive isoform of azurocidin is present in relatively higher amounts and/or is uniquely synthesized by leukemic cells., Thesis, Published.
Quantification of pyrrolizidine alkaloids in North American plants and honey by LC-MS
Pyrrolizidine alkaloids (PAs) are a class of naturally occurring compounds produced by many flowering plants around the World. Their presence as contaminants in food systems has become a significant concern in recent years. For example, PAs are often found as contaminants in honey through pollen transfer. A validated method was developed for the quantification of four pyrrolizidine alkaloids and one pyrrolizidine alkaloidN-oxide in plants and honey grown and produced in British Columbia. The method was optimised for extraction efficiency from the plant materials and then subjected to a single-laboratory validation to assess repeatability, accuracy, selectivity, LOD, LOQ and method linearity. The PA content in plants ranged from1.0 to 307.8 µg/g with repeatability precision between 3.8 and 20.8% RSD. HorRat values were within acceptable limits and ranged from 0.62 to 1.63 for plant material and 0.56–1.82 for honey samples. Method accuracy was determined through spike studies with recoveries ranging from 84.6 to 108.2% from the raw material negative control and from 82.1–106.0 % for the pyrrolizidine alkaloids in corn syrup. Based on the findings in this single-laboratory validation, this method is suitable for the quantitation of lycopsamine, senecionine, senecionineN-oxide, heliosupine and echimidine in common comfrey (Symphytum officinale), tansy ragwort (Senecio jacobaea), blueweed (Echium vulgare) and hound’s tongue (Cynoglossum officinale)and for PA quantitation in honey and found that PA contaminants were present at low levels in BC honey., Peer-reviewed article, Published. Received 4 June 2015; accepted 20 September 2015.
Quantifying the effects of on-the-fly changes of seating configuration on the stability of a manual wheelchair
Proceedings of the 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), in Seogwipo, South Korea, 11-15 July 2017. In general, manual wheelchairs are designed with a fixed frame, which is not optimal for every situation. Adjustable on the fly seating allow users to rapidly adapt their wheelchair configuration to suit different tasks. These changes move the center of gravity (CoG) of the system, altering the wheelchair stability and maneuverability. To assess these changes, a computer simulation of a manual wheelchair was created with adjustable seat, backrest, rear axle position and user position, and validated with experimental testing. The stability of the wheelchair was most affected by the position of the rear axle, but adjustments to the backrest and seat angles also result in stability improvements that could be used when wheeling in the community. These findings describe the most influential parameters for wheelchair stability and maneuverability, as well as provide quantitative guidelines for the use of manual wheelchairs with on the fly adjustable seats., Conference paper, Published.
A quantitative study of cotyledon positioning in conifer development
The number of cotyledons in angiosperm monocots and dicots is tightly constrained. But in the gymnosperm Pinaceae (pine family), which includes many of the conifers, cotyledon number ( nc) can vary widely, commonly from 2 to 12. Conifer cotyledons form in whorled rings on a domed embryo geometry. We measured the diameter of embryos and counted the cotyledons to determine the radial positioning of the whorl and the circumferential spacing between cotyledons. Results were similar between Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco), Sitka spruce ( Picea sitchensis (L.) H.Karst .), and larch ( Larix × leptoeuropaea, synonymous with L. × marschlinsii Coaz), indicating a common mechanism for cotyledon positioning in conifers. Disrupting transport of the growth regulator auxin (with 1- N-naphthylphthalamic acid (NPA)) led to cup-shaped embryos, indicating that whorl (ring) formation is separable from cotyledon patterning within the ring. NPA inhibits cotyledon outgrowth, but not the spacing (distance) between cotyledons. The NPA effect is direct; it does not operate indirectly on embryo size. These results support a hierarchical model for cotyledon positioning in conifers, in which a first stage (not requiring auxin transport) sets the whorl position, constraining the second stage (which requires auxin transport) to form cotyledons within this whorl. Similarly, recent studies in Arabidopsis have shown that different components of complex developmental patterns can have different transport properties; this aspect of patterning may be shared across plants., Peer-reviewed article, Published. Received 27 November 2015. Accepted 8 April 2016.
Ranking functions for belief change
Proceedings of the 6th International Conference on Agents and Artificial Intelligence in Angers, France, 2014. In this paper, we explore the use of ranking functions in reasoning about belief change. It is well-known that the semantics of belief revision can be defined either through total pre-orders or through ranking functions over states. While both approaches have similar expressive power with respect to single-shot belief revision, we argue that ranking functions provide distinct advantages at both the theoretical level and the practical level, particularly when actions are introduced. We demonstrate that belief revision induces a natural algebra over ranking functions, which treats belief states and observations in the same manner. When we introduce belief progression due to actions, we show that many natural domains can be easily represented with suitable ranking functions. Our formal framework uses ranking functions to represent belief revision and belief progression in a uniform manner; we demonstrate the power of our approach through formal results, as well as a series of natural problems in commonsense reasoning., Conference paper, Published.
Raphe-spinal neurons display an age-dependent differential capacity for neurite outgrowth compared to other brainstem-spinal populations
Functional regeneration of brainstem–spinal pathways occurs in the developing chick when the spinal cord is severed prior to embryonic day (E) 13. Functional spinal cord regeneration is not observed in animals injured after E13. This developmental transition from a permissive to a restrictive repair period may be due to the formation of an extrinsic inhibitory environment preventing axonal growth, and/or an intrinsic inability of mature neurons to regenerate. Here, we investigated the capacity of specific populations of brainstem–spinal projection neurons to regrow neurites in vitro from young (E8) versus mature (E17) brainstem explants. A crystal of carbocyanine dye (DiI) was implanted in ovo into the E5 cervical spinal cord to retrogradely label brainstem–spinal projection neurons. Three or 12 days later, discrete regions of the brainstem containing DiI-labeled neurons were dissected to produce explant cultures grown in serum-free media on laminin substrates. The subsequent redistribution of DiI into regenerating processes permitted the study of in vitro neurite outgrowth from identified brainstem–spinal neurons. When explanted on E8, i.e., an age when brainstem–spinal neurons are normally elongating through the spinal cord and are capable of in vivo functional regeneration, robust neurite outgrowth was observed from all brainstem populations, including rubro-, reticulo-, vestibulo-, and raphe–spinal neurons. In contrast, when explanted on E17, robust neurite outgrowth was seen only from raphe-spinal neurons. Neurite outgrowth from raphe-spinal neurons was 5-hydroxy-tryptamine immunoreactive. This study demonstrates that in growth factor-free environments with permissive growth substrates, neurite outgrowth from brainstem–spinal neurons is dependent on both neuronal age and phenotype., Peer-reviewed article, Published. Received 22 February 2000; Accepted 25 May 2000; Available online 25 May 2002.
Real-time adaptive optimization engine algorithm for integrated Volt/VAr optimization and conservation voltage reduction of smart microgrids
Proceedings from CIGRÉ Canada Conference, Montreal, Sept. 2012. In recent decade, smart microgrids have raised the feasibility and affordability of adaptive and real-time Volt/VAr optimization (VVO) and Conservation Voltage Reduction (CVR) implementations by their exclusive features such as using smart metering technologies and various types of dispersed generations. Smart distribution networks are presently capable of achieving higher degrees of efficiency and reliability through employing a new integrated Volt/VAr optimization system. For VVO application, two well-known approaches are recommended by different utilities and/or companies: Centralized VVO and Decentralized VVO. In centralized VVO, the processing system is placed in a central controller unit such as DMS in the so called “Utility Back Office”. The DMS uses relevant measurements taken from termination points (i.e. utility subscribers) supplied to it from either field collectors or directly from MDMS, to determine the best possible settings for field-bound VVO/CVR assets to achieve the desired optimization and conservation targets. These settings are then off-loaded to such assets through existing downstream pipes, such as SCADA network In contrast, decentralized VVO utilizes VVO/CVR engines which are located in the field and in close-proximity to the relevant assets to conserve voltage and energy according to local attributes of the distribution network. In this case, local measurements do not need to travel from the field to the back-office, and the new settings for VVO/CVR assets are determined locally, rather than from a centralized controller. Without having any preference between above mentioned VVO techniques, this paper studies an adaptive optimization engine for real-time VVO/CVR in smart microgrids based on Intelligent Agent technology. The optimization algorithm provides the best optimal solution for VVO/CVR problem at each real-time stage through minimizing system loss cost and improves system energy efficiency as well as voltage profile of the relevant distribution system. The algorithm may employ distributed generation sources to address the Volt/VAr optimization problem in real-time. Coordinated VVO/CVR requires real-time data analysis every 15 minutes. It utilizes a distributed command and control architecture to supply the VVO Engine (VVOE) with the required data, and secures real-time configuration from the VVO engine for the VVO control devices such as On-Load Tap Changers (OLTCs), Voltage Regulators (VRs) and Capacitor Banks (CBs). It also has the option of employing distributed generation (DG) as well as modelling load effects in VVO/CVR application. The algorithm minimizes the distribution network power loss cost at each time stage, checks the voltage deviation of distribution buses and distributed generation sources considering different types of constraints such as system power flow, distribution network power factor, system active and reactive power constraints and switching limitations of Volt/VAr control devices. The algorithm receives required real-time data from an intelligent agent. Then, it starts to solve the real-time VVO/CVR problem in order to find the best optimal configuration of the network in real-time. The paper uses British Columbia Institute of Technology (BCIT) distribution network as its case study in order to explore the effectiveness and the accuracy of the optimization engine. Moreover, the VVO/CVR optimization algorithm is implemented in different configurations; a) VVO/CVR confined to the substation and b) VVO/CVR optimization algorithm within the substation and along distribution feeders. The algorithm also checks the availability of DGs to assist VVO/CVR control functions and assesses the impact of new distributed sources such as: Flywheel Energy Storage System (FESS) on real-time VVO/CVR. For this reason, the algorithm classified DGs in a microgrid based on their impacts and instantiates them based on their application feasibility for real-time VVO/CVR., Conference paper, Published.
Real-time co-simulated platform for novel Volt-VAR Optimization of smart distribution network using AMI data
Accepted in IEEE International Conference on Smart Energy Grid Engineering, May 2015. This paper presents a real-time co-simulated platform for novel voltage and reactive power optimization (VVO) of distribution grids through a real-time digital simulator (RTDS) in presence of a reliable communication platform. The proposed VVO engine is able to capture quasi real-time data from local Advanced Metering Infrastructure (AMI) and optimizes the distribution network for each quasi real-time stage (every 5 minutes) based on system main characteristics (i.e. active/reactive power of nodes). At each time stage, the VVO engine tries to minimize losses in the distribution network as well as to improve the voltage profile of the system. In order to test robustness, performance and the applicability of proposed Volt-VAR Optimization engine, a 33 node distribution network has been modeled and studied in a real-time Co-simulated environment by real-time simulator (RTDS) and a real communication platform with DNP.3 protocol. The preliminary results prove well-performance of proposed AMI-based VVO engine and show that the engine enables system to achieve higher level of loss/operating cost reduction through a sophisticated optimization engine compare with conventional approaches., Conference paper, Published.
Real-time communication platform for Smart Grid adaptive Volt-VAR Optimization of distribution networks
Proceeding of IEEE International Conference on Smart Energy Grid Engineering (SEGE), Aug. 2015, Oshawa, ON, Canada. This paper investigates a real-time communication platform for a Smart Grid adaptive Volt-VAR Optimization (VVO) engine. Novel VVO techniques receive inputs from Advanced Metering Infrastructure (AMI) to dynamically optimize distribution networks. As communication platform design and characteristics affect Smart Grid-based VVO performance in terms of control accuracy and response time, VVO ICT studies is essential for grid planners and/or power utilities. Hence, this paper primarily introduces a real-time co-simulated environment comprised of Smart Grid adaptive VVO engine, RTDS model and system communication platform using DNP3 protocol. This platform is built to test and asses the influence of different components included in Smart Grid monitoring and control system; namely the sensors, measurement units, communication infrastructure on the operation and control of VVO. Moreover, this paper uses a real-time platform to check the robustness of the monitoring and control applications for communication network considerations such as delays and packet loss. Next, this paper investigates how such a platform could look into communication issues while taking system requirements into consideration. A 33-node distribution feeder is employed to check system performance through communication parameters such as throughput and response time., Conference paper, Published.
Real-time control of a video game with a direct brain-computer interface
Mason and Birch have developed a direct brain–computer interface for intermittent control of devices such as environmental control systems and neuroprotheses. This EEG-based brain switch, named the LF-ASD, has been used in several off-line studies, but little is known about its usability with real-world devices and computer applications. In this study, able-bodied individuals and people with high-level spinal injury used the LF-ASD brain switch to control a video game in real time. Both subject groups demonstrated switch activations varying from 30% to 78% and false-positive rates in the range of 0.5% to 2.2% over three 1-hour test sessions. These levels correspond to switch classification accuracies greater than 94% for all subjects. The results suggest that subjects with spinal cord injuries can operate the brain switch to the same ability as able-bodied subjects in a real-time control environment. These results support the findings of previous studies., Peer-reviewed article, Published.

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