The in vivo application of appropriate trophic factors may enhance regeneration of bulbospinal projections after spinal cord injury. Currently, little is known about the sensitivities of specific bulbospinal neuron populations to the many identified trophic factors. We devised novel in vitro assays to study trophic effects on the survival and neurite outgrowth of identified bulbospinal neurons. Carbocyanine dye crystals implanted into the cervical spinal cord of embryonic day (E)5 chick embryos retrogradely labeled developing bulbospinal neurons. On E8, dissociated cultures containing labeled bulbospinal neurons were prepared. Fibroblast growth factor (FGF)-2 (but not FGF-1) promoted the survival of bulbospinal neurons. FGF receptor expression was widespread in the E8 brainstem, but not detected in young bulbospinal neurons, suggesting that nonneuronal cells mediated the FGF-stimulated survival response. Astrocytes synthesize a variety of trophic factors, and astrocyte-conditioned medium (ACM) also promoted the survival of bulbospinal neurons. As might be expected, FGF-2 function blocking antibodies did not suppress ACM-promoted survival, nor did an ELISA detect FGF-2 in ACM. This suggests that nonneuronal cells synthesize other factors in response to exogenous FGF-2 which promote the survival of bulbospinal neurons. Focusing on vestibulospinal neurons, dissociated (survival assay) or explant (neurite outgrowth assay) cultures were prepared. FGF-2 promoted both survival and neurite outgrowth of identified vestibulospinal neurons. Interestingly, FGF-1 promoted neurite outgrowth but not survival; the converse was true of FGF-9. Thus, differential effects of specific growth factors on survival or neurite outgrowth of bulbospinal neurons were distinguished., Peer-reviewed article, Published. Received 10 September 1999; Accepted 18 January 2000; Available online 25 May 2002.
The functional level (K level) of prosthetic users is used to choose appropriate prosthetic components, but ratings may highly subjective. A more objective and robust method to determine K level may be appealing. The aim of this study was to determine the relationship between K level determined in the clinic to K level based on real world ambulatory activity data collected by StepWatch. Twelve individuals with transtibial limb loss gave informed consent to participate. K level assessments performed in the clinic by a single treating prosthetist were compared with a calculated estimate based on seven days of real world ambulatory activity patterns using linear regression. There was good agreement between the two methods of determining K level with R2 = 0.775 (p < 0.001). The calculated estimate of K level based on actual ambulatory activity in real world settings appears to be similar to the treating prosthetist’s assessment of K level based on gait observation and patient responses in the clinic. Clinic-based ambulatory capacity in transtibial prosthetic users appears to correlate with real world ambulatory behavior in this small cohort. Determining functional level based on real world ambulatory activity may supplement clinic-based tests of functional capacity., Peer-reviewed article, Published. Date received: 2 December 2015; Accepted: 20 January 2016; First Published March 9, 2016.
Describes research work directed towards the development and application of a design methodology to determine the optimal configuration of a powered upper-limb orthosis. The design objective was to minimize the orthosis complexity, defined as the number of degrees of freedom, while maintaining the ability to perform specific tasks. This objective was achieved in three stages. First, potential users of a powered orthosis were interviewed to determine their priority tasks. Secondly, the natural arm motions of able-bodied individuals performing the priority tasks were profiled using a video tracking system. Finally, a kinematic simulation algorithm was developed and employed in order to evaluate whether a proposed orthosis configuration could perform the priority tasks. The research results indicate that task functionality is overly compromised for orthosis configurations with less than five degrees of freedom, plus prehension. Acceptable task performance, based on the specific priority tasks considered, was achieved in the simulations of two different orthosis configurations with five degrees of freedom. In the first design option, elevation (rotation about a horizontal axis through the shoulder) and radial/ulnar deviation are fixed, while in the second option wrist flexion and radial/ulnar deviation are fixed. A prototype orthosis is currently being developed using the first design option., Peer-reviewed article, Published.
Proceedings of 2011 21st International Conference on Noise and Fluctuations in Toronto, ON, Canada on 12-16 June 2011. Fruit flies serve as a model for understanding the genetic regulation involved in specifying the complex body plans of higher animals. The head-to-tail (anterior-posterior) axis of the fly (Drosophila) is established in the first hours of development. Maternally supplied factors form concentration gradients which direct embryonic (zygotic) genes where to be activated to express proteins. These protein patterns specify the positions and cell types of the body's tissues. Recent research has shown, comparing between embryos, that the zygotic gene products are much more precisely positioned than the maternal gradients, indicating an embryonic error reduction mechanism. Within embryos, there is the additional aspect that DNA and mRNA operate at very low copy number, and the associated high relative noise has the potential to strongly affect protein expression patterns. In recent work, we have focused on the noise aspects of positional specification within individual embryos. We simulate activation of hunchback (hb), a primary target of the maternal Bicoid (Bcd) protein gradient, which forms an expression pattern dividing the embryo into anterior and posterior halves. We use a master equation approach to simulate the stochastic dynamics of hb regulation, using the known details of the hb promoter, the region of DNA responsible for transcribing hb mRNA. This includes the binding/unbinding of Bcd molecules at the promoter, hb transcription, subsequent translation to Hb protein, binding/unbinding of Hb at the promoter (self-regulation), and diffusion of the Bcd and Hb proteins. Model parameters were set by deterministically matching large scale pattern features for a series of experimental expression patterns: wild-type (WT) embryos; hb mutants lacking self-regulation; and constructs in which portions of the hb promoter were used to express a reporter gene (lacZ). The model was then solved stochastically to predict the noise output in these different experiments. In subsequent noise measurements we experimentally corroborated a number of the predictions. These include that mRNA is noisier than protein, and that Hb self-regulation reduces noise. Results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, and is uncorrelated with Bcd fluctuations. This contradicts prior work, which had assumed a complete dependence of Hb fluctuations on Bcd fluctuations. In the constructs and mutant, which lack self-regulation, we find that increasing the number and strength of Bcd binding sites (there are 6 in the core hb promoter) provides a rudimentary level of noise reduction. The model is robust to the various Bcd binding site numbers seen across different fly species. New directions in the project include incorporating a known inhibitor of hb, Krüppel, into the model to study its effect on the noise dynamics. Our study has identified particular ways in which hb output noise is controlled. Since these involve common modes of gene regulation (e.g. multiple regulatory sites, self-regulation), these results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development., Conference paper, Published.
Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F), and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e.g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development., Peer-reviewed article, Publisher. Received July 4, 2010; Accepted December 28, 2010; Published February 3, 2011.
Computer support for conceptual structural design is still ineffective. This is due, in part, to the fact that current computer applications do not recognize that structural design and architectural design are highly interdependent processes, particularly at the early stages. The goal of this research is to assist structural engineers at the conceptual stage with early digital architectural models. This paper presents a geometric modeling framework for facilitating the engineers’ interactions with architectural models in order to detect potential structural problems, uncover opportunities, respect constraints, and ultimately synthesize structural solutions interactively with architectural models. It consists of a process model, a representation model and synthesis algorithms to assist the engineer on demand at different stages of the design process. The process model follows a top-down approach for design refinements. The representation model describes the structural system as a hierarchy of entities with architectural counterparts. The algorithms rely on geometric and topologic relationships between entities in the architectural model and a partial structural model to help advance the synthesis process. A prototype system called StAr (Structure–Architecture) implements this framework. A case study illustrates how the framework can be used to support the conceptual structural design process., Peer reviewed, Peer reviewed article, Received 24 October 2005 ; Revised 5 February 2007 ; Accepted 8 March 2007 ; Available online 3 December 2007., Geometric modeling, Conceptual structural design, Integrated design, Architectural design
One-planet living represents the per capita share of global ecosystem services that each person on Earth could use were humanity to live equitably within ecological carrying capacity. My research uses ecological footprint analysis to explore the potential for the City of Vancouver to achieve one-planet living. Specifically, I examine what reductions in per capita ecological footprint would be necessary, what policies or changes to management practices are available to the City to facilitate those reductions, and what one-planet living might “look like” if those policies and changes to urban management practices were implemented. I use 2006 data to conduct an integrated urban metabolism and ecological footprint assessment for the City in order to establish a baseline from which to estimate the necessary reductions in material and energy consumption. I develop lifestyle archetypes of societies living at a one-planet ecological footprint (both real and hypothetical) to inform estimates on how changes in diet, buildings, consumables and waste, transportation and water could achieve one-planet living in Vancouver. I also draw on examples from the international sustainable cities literature and interviews with City of Vancouver and Metro Vancouver staff and elected representatives to develop policy proposals for reducing Vancouver’s ecological footprint. Getting to one-planet living in Vancouver requires at least a 58% reduction in the per capita ecological footprint with the greatest contributions coming from reducing food waste, red meat consumption, and virtually eliminating personal motor vehicle use (shifting instead to an 86% walk, cycle and transit mode share which the City already achieves in its Downtown). The City has and can continue to influence individual and corporate choices through zoning and permitting. However, citizens would have to accept lifestyle changes pertaining to food and personal consumption to achieve the one-planet living goal. Involvement by senior governments in reducing the ecological footprint is also required. It remains to be seen whether Vancouverites, or any population accustomed to modern consumer lifestyles, will voluntarily accept and implement the changes necessary to achieve equitable sustainability as articulated by one-planet living., Thesis, Published.
Ecological Footprint Analysis (EFA) at the city or regional scale does not typically include air travel due to a lack of readily available data. However, knowing the “load” placed on nature by various lifestyle choices, including air travel, is essential if we hope to enable society to live sustainably within ecological limits. This paper provides methods for including air travel in urban EFA, in a manner that is accessible to those that are interested in the complexities of urban sustainability. Our goal is to use the case of the Vancouver Metropolitan region to illustrate two methods in such a way that they can be replicated or adapted for use in other cities and regions. We found that the greenhouse gas emissions of air travel by Metro Vancouver residents for 2006 is between 1,191,070 and 1,402,420 tonnes of carbon dioxide equivalent (tCO2e). The resulting ecological footprint is between 287,030 and 337,980 global hectares (gha), or between 0.136 and 0.160 gha/capita. The dedicated carbon sink required to neutralize the carbon dioxide emissions from Metro Vancouver residents’ air travel alone is equivalent to twice the land area of the region (283,183 hectares)., Peer-reviewed article, Published. Received: July 15, 2013 ; Accepted: September 16, 2013 ; Online Published: September 27, 2013.
Hygrothermal models are emerging as practical building design tools. These models require a set of reliable inputs to provide results that are meaningful to the designers. One of these inputs is the set of heat, air and moisture transport properties of materials. For any given class of building materials the properties may vary within a broad range. This paper reports the porosity, density, matrix density, thermal conductivity, equilibrium moisture content, water vapor permeability, water absorption coefficient, liquid diffusivity and air permeability of six types of bricks and four mortar mixes that are commonly used in North America. The experimental and analytical procedures follow either international standards or well-established methodologies., Peer reviewed article, Published. Received 9 July 2003; accepted 17 March 2004.
Heat, air, and moisture transfer models that are used as practical building design tools require reliable inputs to provide meaningful results. One of these inputs is the set of heat, air, and moisture transport properties of materials. For any given class of building materials the properties may vary within a broad range. This paper reports the porosity, density, matrix density, thermal conductivity, equilibrium moisture content, water vapor permeability, water absorption coefficient, liquid diffusivity, and air permeability of regular lime stucco, regular Portland cement stucco, and acrylic stucco that are commonly used in North America. The experimental and analytical procedures follow either international standards or well-established methodologies., Peer reviewed article, Published. Received 9 January 2004; accepted 13 October 2005; published online 25 January 2006.
The feasibility of meeting emission targets is often evaluated using long range planning optimization models in which the targets are incorporated into the system constraints. These models typically provide one ‘optimal’ solution that considers only a deterministic representative value of emissions for each technology and do not consider the risk of exceeding expected emissions for a given optimal solution. Since actual emissions for any given technology are uncertain, implementation of such an optimal solution carries inherent risk that emissions will exceed the given target. In this paper, we implement a stochastic risk structure into the OSeMOSYS optimization model to incorporate uncertainty related to the emissions of electricity generation technologies. For a given risk premium, defined as the additional amount that society is willing to pay to reduce the risk of exceeding the cost optimal system emissions, we determine the generation technology mix that has the lowest risk of exceeding this baseline. We focus on emissions risk since the literature on emissions risk is sparse while the literature on other risks such as policy risks, financial risks and technological risks is extensive.
We apply the model to a case study of a primarily fossil based jurisdiction and find that, when risk is incorporated, solar and wind technologies are built out seven and five years earlier respectively and that carbon free technologies such as coal with carbon capture and storage (CCS) become effective alternatives in the energy mix when compared to the ‘optimal’ solution without consideration of risk, though this does not include the risk of carbon leakage from CCS technologies. If nuclear is included as a generation option, we find that nuclear provides an effective risk hedge against exceeding emissions., Peer-Reviewed Article, Final article published. Available online 12 February 2017., Peer reviewed