71 research outputs found

    Seismic Design of Tialings Dam An Overview of its Evolution and New Challenges

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    This paper first provides an overview of the evolution of tailings dam engineering over the years. It then highlights key factors affecting seismic performance of tailings dams: such as site seismicity, foundation and damfill geotechnical characteristics, dam design, construction, operation and decommissioning, seismic slope stability, and dam rehabilitation. Finally, it reviews some of the recent trends that lead to new challenges to the engineering profession. These challenges include: coping with heightened public concern about dam safety; balancing potential conflict between seismic and environmental requirements; and addressing issues introduced by globalisation of the mining industry. Institutional responses and technological tools available to meet these challenges are outlined

    Seismic Assessment of Syncrude Tailings Dyke

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    This paper describes the assessment of seismic risk at the Syncrude Site. It reviews the site physiographic and geologic setting and considers the site position relative to observed seismic events, strain release patterns, and main tectonic features in western Canada. Both deterministic and probabilistic approaches were employed in the seismic risk assessment. Data on seismic events that occurred between 1899 and 1985 were included in the evaluation. Of particular importance was determination of the impact on the site of a series of large earthquakes which occurred in the Nahanni area of the Northwest Territories during 1985. Hasegawa et al. (1981) attentuation relations were used for computing ground motion amplitudes at the site. The review confirmed that the seismic risk at the Syncrude Site remains low

    Overview of Highland Valley Tailings Storage Facility

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    This paper presents key features of the Highland Valley tailings storage facility comprising two tailings dams, a 107 m high H-H Dam and a 166 m high L-L Dam. The construction history to date including instrumentation observations is also reviewed. Although the tailings facility is situated in a low to moderate seismic area within the Interior Plateau of British Columbia, potential earthquake sources that might have an impact on the site have been carefully assessed. Both dams are designed to have adequate seismic resistance against design earthquakes appropriate for the site. The L-L Dam valley section, involving soft lacustrine deposits beneath the Starter Dam, has been buttressed by a compacted downstream berm founded on dense glacial till. As the geometry of the tailings storage and distribution facilities and waste dumps changes with time, the quantity and relative cost of various construction materials including natural borrow, cycloned sand and pit overburden also change. Ongoing construction is planned to maintain key earthquake and flood design criteria as well as to adjust the use and placement method of various materials to achieve an efficient and cost effective tailings storage operation. Inherent in the design of the two tailings dams, both constructed by the centerline method, is the flexibility which enables the storage capacity of the tailings facility to be increased beyond the present 1.8 billion tonnes if required at some future time

    Physical, chemical and kinetic factors affecting prion infectivity

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    The mouse-adapted scrapie prion strain RML is one of the most widely used in prion research. The introduction of a cell culture-based assay of RML prions, the scrapie cell assay (SCA) allows more rapid and precise prion titration. A semi-automated version of this assay (ASCA) was applied to explore a range of conditions that might influence the infectivity and properties of RML prions. These include resistance to freeze-thaw procedures; stability to endogenous proteases in brain homogenate despite prolonged exposure to varying temperatures; distribution of infective material between pellet and supernatant after centrifugation, the effect of reducing agents and the influence of detergent additives on the efficiency of infection. Apparent infectivity is increased significantly by interaction with cationic detergents. Importantly, we have also elucidated the relationship between the duration of exposure of cells to RML prions and the transmission of infection. We established that the infection process following contact of cells with RML prions is rapid and followed an exponential time course, implying a single rate-limiting process

    Anti-prion drug mPPIg5 inhibits PrP(C) conversion to PrP(Sc).

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    Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future

    Developing a health and human rights training program for french speaking Africa: lessons learned, from needs assessment to a pilot program

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    <p>Abstract</p> <p>Background</p> <p>The importance of human rights education has widely been recognized as one of the strategies for their protection and promotion of health. Yet training programs have not always taken into account neither local needs, nor public health relevance, nor pedagogical efficacy.</p> <p>The objectives of our study were to assess, in a participative way, educational needs in the field of health and human rights among potential trainees in six French-speaking African countries and to test the feasibility of a training program through a pilot test. Ultimately the project aims to implement <it>a health and human rights training program most appropriate to the African context</it>.</p> <p>Methods</p> <p><it>Needs assessment </it>was done according to four approaches: Revue of available data on health and human rights in the targeted countries; Country visits by one of the authors meeting key institutions; Focus group discussions with key-informants in each country; A questionnaire-based study targeting health professionals and human rights activists.</p> <p><it>Pilot training program</it>: an interactive e-learning pilot program was developed integrating training needs expressed by partner institutions and potential trainees.</p> <p>Results</p> <p>Needs assessment showed high public health and human rights challenges that the target countries have to face. It also showed precise demands of partner institutions in regard to a health and human rights training program. It further allowed defining training objectives and core competencies useful to potential employers and future students as well as specific training contents.</p> <p>A pilot program allowed testing the motivation of students, the feasibility of an interactive educational approach and identifying potential difficulties.</p> <p>Conclusion</p> <p>In combining various approaches our study was able to show that training needs concentrate around tools allowing the identification of basic human rights violations in the health system, the analysis of their causes and coordinated responses through specific intervention projects.</p

    Ubiquinone Analogs: A Mitochondrial Permeability Transition Pore-Dependent Pathway to Selective Cell Death

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    International audienceBACKGROUND: Prolonged opening of the mitochondrial permeability transition pore (PTP) leads to cell death. Various ubiquinone analogs have been shown to regulate PTP opening but the outcome of PTP regulation by ubiquinone analogs on cell fate has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: The effects of ubiquinone 0 (Ub(0)), ubiquinone 5 (Ub(5)), ubiquinone 10 (Ub(10)) and decyl-ubiquinone (DUb) were studied in freshly isolated rat hepatocytes, cultured rat liver Clone-9 cells and cancerous rat liver MH1C1 cells. PTP regulation by ubiquinones differed significantly in permeabilized Clone-9 and MH1C1 cells from that previously reported in liver mitochondria. Ub(0) inhibited PTP opening in isolated hepatocytes and Clone-9 cells, whereas it induced PTP opening in MH1C1 cells. Ub(5) did not affect PTP opening in isolated hepatocytes and MH1C1 cells, but it induced PTP opening in Clone-9 cells. Ub(10) regulated PTP in isolated hepatocytes, whereas it did not affect PTP opening in Clone-9 and MH1C1 cells. Only DUb displayed the same effect on PTP regulation in the three hepatocyte lines tested. Despite such modifications in PTP regulation, competition between ubiquinones still occurred in Clone-9 and MH1C1 cells. As expected, Ub(5) induced a PTP-dependent cell death in Clone-9, while it did not affect MH1C1 cell viability. Ub(0) induced a PTP-dependent cell death in MH1C1 cells, but was also slightly cytotoxic in Clone-9 by an oxidative stress-dependent mechanism. CONCLUSIONS/SIGNIFICANCE: We found that various ubiquinone analogs regulate PTP in different ways depending on the cell studied. We took advantage of this unique property to develop a PTP opening-targeted strategy that leads to cell death specifically in cells where the ubiquinone analog used induces PTP opening, while sparing the cells in which it does not induce PTP opening

    The Comprehensive Native Interactome of a Fully Functional Tagged Prion Protein

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    The enumeration of the interaction partners of the cellular prion protein, PrPC, may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrPC. When expressed in transgenic mice, PrPmyc carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrPC. PrPmyc antagonized the toxicity of truncated PrP, restored prion infectibility of PrPC-deficient mice, and was physically incorporated into PrPSc aggregates, indicating that it possessed all functional characteristics of genuine PrPC. We then immunopurified myc epitope-containing protein complexes from PrPmyc transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrPC and may represent component of a multiprotein complex. Selected PrPC interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance
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