Ice-binding proteins adsorb to their ligand via anchored clathrate waters

The main success of my thesis has been to establish the mechanism by which antifreeze proteins (AFPs) bind irreversibly to ice crystals, and hence prevent their growth. AFPs organize ice-like water on their ice-binding site, which then merges and freezes with the quasi-liquid layer of ice. This was revealed from studying the exceptionally large (ca. 1.5-MDa) Ca 2+-dependent AFP from the Antarctic bacterium Marinomonas primoryensis (MpAFP). The 34-kDa antifreeze- active region of MpAFP was predicted to fold as a novel Ca 2+-binding β-helix. Site-directed mutagenesis confirmed the model and demonstrated that its ice-binding site (IBS) consisted of solvent-exposed Thr and Asx parallel arrays on the Ca 2+-binding turns. The X-ray crystal structure of the antifreeze region was solved to a resolution of 1.7 Å. Two of the four molecules within the unit cell of the crystal had portions of their IBSs freely exposed to solvent. Identical clathrate-like cages of water molecules were present on each IBS. These waters were organized by the hydrophobic effect and anchored to the protein via hydrogen bonds. They matched the spacing of water molecules in an ice lattice, demonstrating that anchored clathrate waters bind AFPs to ice. This mechanism was extended to other AFPs including the globular type III AFP from fishes. Site-directed mutagenesis and a modified ice-etching technique demonstrated this protein uses a compound ice-binding site, comprised of two flat and relatively hydrophobic surfaces, to bind at least two planes of ice. Reinvestigation of several crystal structures of type III AFP identified anchored clathrate waters on the solvent-exposed portion of its compound IBS that matched the spacing of waters on the primary prism plane of ice. Ice nucleation proteins (INPs), which can raise the temperature at which ice forms in solution to just slightly below 0oC, have the opposite effect to AFPs. A novel dimeric β-helical model was proposed for the INP produced by the bacterium Pseudomonas borealis. Molecular dynamics simulations showed that INPs are also capable of ordering water molecules into an ice- like lattice. However, their multimerization brings together sufficient ordered waters to form an ice nucleus and initiate freezing.

The Economic Case for Electric Mining Equipment and Technical Considerations Relating to their Implementation

Underground hardrock mining can be very energy intensive and in large part this can be attributed to the power consumption of underground ventilation systems. In general, the power consumed by a mine’s ventilation system and its overall scale are closely related to the amount of diesel power in operation. This is because diesel exhaust is a major source of underground air pollution, including diesel particulate matter (DPM), NO2 and heat, and because regulations tie air volumes to diesel engines. Furthermore, assuming the size of airways remains constant, the power consumption of the main system increases exponentially with the volume of air supplied to the mine. Therefore large diesel fleets lead to increased energy consumption and can also necessitate large capital expenditures on ventilation infrastructure in order to manage power requirements. Meeting ventilation requirements for equipment in a heading can result in a similar scenario with the biggest pieces leading to higher energy consumption and potentially necessitating larger ventilation tubing and taller drifts. Depending on the climate where the mine is located, large volumes of air can have a third impact on ventilation costs if heating or cooling the air is necessary. Annual heating and cooling costs, as well as the cost of the associated infrastructure, are directly related to the volume of air sent underground. This thesis considers electric mining equipment as a means for reducing the intensity and cost of energy consumption at underground, hardrock mines. Potentially, electric equipment could greatly reduce the volume of air needed to ventilate an entire mine as well as individual headings because they do not emit many of the contaminants found in diesel exhaust and because regulations do not connect air volumes to electric motors. Because of the exponential relationship between power consumption and air volumes, this could greatly reduce the amount of power required for mine ventilation as well as the capital cost of ventilation infrastructure. As heating and cooling costs are also directly linked to air volumes, the cost and energy intensity of heating and cooling the air would also be significantly reduced. A further incentive is that powering equipment from the grid is substantially cheaper than fuelling them with diesel and can also produce far fewer GHGs. Therefore, by eliminating diesel from the underground workers will enjoy safer working conditions and operators and society at large will gain from a smaller impact on the environment. Despite their significant potential, in order to produce a credible economic assessment of electric mining equipment their impact on underground systems must be understood and considered in their evaluation. Accordingly, a good deal of this thesis reviews technical considerations related to the use of electric mining equipment, especially ones that impact the economics of their implementation. The goal of this thesis will then be to present the economic potential of implementing the equipment, as well as to outline the key inputs which are necessary to support an evaluation and to provide a model and an approach which can be used by others if the relevant information is available and acceptable assumptions can be made.

Measuring Solar Energy Potentials in Residential Environments: A Comparative Study of Three Neighbourhoods in Kingston, Ontario

Photovoltaic (PV) systems offer a way to generate electricity locally in an urban setting while avoiding the environmental impacts of more widely used energy sources such as oil, coal, nuclear and natural gas. This report attempts to measure the benefits of incorporating solar technologies into urban residential land uses and identifies challenges to their widespread use by comparing implementation among three distinct residential neighbourhoods common to Canadian cities. The City of Kingston, Ontario is used as the location for this study.

Self-Management of Chronic Pain: Interventions, Strategies, Barriers, and Facilitators

Background & Purpose: Chronic pain is a prevalent chronic condition for which the best management options rarely provide complete relief. Individuals with chronic pain with neuropathic characteristics (NC) report more severe pain and experience less relief from interventions. Little is known about current self-management practices. The purpose of this dissertation was to inform self-management of chronic pain with and without NC at the individual, health system, and policy levels using the Innovative Care for Chronic Conditions Framework. Methods: The study included a systematic search and review and cross-sectional survey. The review evaluated the evidence for chronic pain self-management interventions and explored the role of health care providers in supporting self-management. The survey was mailed to 8,000 randomly selected Canadians in November 2011, and non-respondents were followed-up in May 2012. Screening questions were included for both chronic pain and NC. The questionnaire captured pain descriptions, self-management strategies, and self-management barriers, and facilitators. Results: Findings of the review suggested that self-management interventions are effective in improving pain and health outcomes. Health care professionals provided self-management advice and referred individuals to self-management interventions. The questionnaire was completed by 1,520 Canadians. Those with chronic pain (n=710) identified primary care physicians as the most helpful pain management professional. Overall, use of non-pharmaceutical medical self-management strategies was low. While use positive emotional self-management strategies was high, individuals with NC were more likely to use negative emotional self-management strategies compared to those without NC. Multiple self-management barriers and facilitators were identified, however those with NC were more likely than those without NC to experience low self-efficacy, depression and severe pain which may impair the ability to self-management. Conclusions: Health care professionals have the opportunity to improve chronic pain outcomes by providing self-management advice, referring to self-management interventions, and addressing self-management barriers and facilitators. Individuals with NC may require additional health services to address their greater self-management challenges, and further research is needed to identify non-pharmaceutical interventions effective in relieving chronic pain with NC. Public policy is needed to facilitate health systems in providing long-term self-management support for individuals with chronic pain.

Challenges, Strengths and Opportunities Related to Implementing Comprehensive Evidence-Based Guidelines on Breast Cancer Survivorship Care by Primary Care Physicians and Nurse Practitioners in Southeastern Ontario

Background Many breast cancer survivors continue to have a broad range of physical and psychosocial problems after breast cancer treatment. As cancer centres move forward with earlier discharge of stable breast cancer survivors to primary care follow-up it is important that comprehensive evidence-based breast cancer survivorship care is implemented to effectively address these needs. Research suggests primary care providers are willing to provide breast cancer survivorship care but many lack the knowledge and confidence to provide evidence-based care. Purpose The overall purpose of this thesis was to determine the challenges, strengths and opportunities related to implementing comprehensive evidence-based breast cancer survivorship guidelines by primary care physicians and nurse practitioners in southeastern Ontario. Methods This mixed-methods research was conducted in three phases: (1) synthesis and appraisal of clinical practice guidelines relevant to provision of breast cancer survivorship care within the primary care practice setting; (2) a brief quantitative survey of primary care providers to determine actual practices related to provision of evidence-based breast cancer survivorship care; and (3) individual interviews with primary care providers about the challenges, strengths and opportunities related to provision of comprehensive evidence-based breast cancer survivorship care. Results and Conclusions In the first phase, a comprehensive clinical practice framework was created to guide provision of breast cancer survivorship care and consisted of a one-page checklist outlining breast cancer survivorship issues relevant to primary care, a three-page summary of key recommendations, and a one-page list of guideline sources. The second phase identified several knowledge and practice gaps, and it was determined that guideline implementation rates were higher for recommendations related to prevention and surveillance aspects of survivorship care and lowest related to screening for and management of long-term effects. The third phase identified three major challenges to providing breast cancer survivorship care: inconsistent educational preparation, provider anxieties, and primary care burden; and three major strengths or opportunities to facilitate implementation of survivorship care guidelines: tools and technology, empowering survivors, and optimizing nursing roles. A better understanding of these challenges, strengths and opportunities will inform development of targeted knowledge translation interventions to provide support and education to primary care providers.