1,217 research outputs found

    Truck transport emissions model

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    In the past, transportation related economic analysis has considered agency related costs only. However, transportation managers are moving towards more holistic economic analysis including road user and environmental costs and benefits. In particular, transportation air pollution is causing increasing harm to health and the environment. Transport managers are now considering related emissions in transport economical analyses, and have established strategies to help meet Kyoto Protocol targets, which specified a fifteen percent reduction in Canada's emissions related to 1990 levels within 2008-2012.The objectives of this research are to model heavy vehicle emissions using a emissions computer model which is able to assess various transport applications, and help improve holistic economic transport modeling. Two case studies were evaluated with the model developed.Firstly, the environmental benefits of deploying weigh-in-motion systems at weigh stations to pre-sort heavy vehicles and reduce delays were assessed. The second case study evaluates alternative truck sizes and road upgrades within short heavy oilfield haul in Western Canada. The model developed herein employed a deterministic framework from a sensitivity analysis across independent variables, which identified the most sensitive variables to primary field state conditions. The variables found to be significant included idling time for the weigh-in-motion case study, road stiffness and road grades for the short heavy haul oilfield case study.According to this research, employing WIM at weigh stations would reduce annual Canadian transportation CO2 emissions by nearly 228 kilo tonnes, or 1.04 percent of the Canadian Kyoto Protocol targets. Regarding direct fuel savings, WIM would save from 90 to 190 million litres of fuel annually, or between 59and59 and 190 million of direct operating costs.Regarding the short heavy oil haul case study, increasing allowable heavy vehicle sizes while upgrading roads could decrease the annual emissions, the fuel consumption, and their associated costs by an average of 68 percent. Therefore, this could reduce each rural Saskatchewan municipality's annual CO2 emissions from 13 to 26.7-kilo tonnes, which translates to 0.06 and 0.12 percent of the Canadian Kyoto Protocol targets or between 544,000and544,000 and 1.1 million annually. Based on these results, the model demonstrates its functionality, and was successfully applied to two typical transportation field state applications. The model generated emissions savings results that appear to be realistic, in terms of potential Kyoto targets, as well as users cost reductions and fuel savings

    Giant kelp forests of the Falkland Islands - a metapopulation structured by past historical colonization events and by present habitat continuity and oceanographic transportation

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    The genetic structure of Macrocystis pyrifera around the Falkland Islands and the Magallean region was determined. In fact, genetic discontinuities related to biogeographic breaks and the role of predictors such as habitat continuity, dispersal, oceanographic currents, and bathymetry were assessed to understand the metapopulation’s structure around the Falklands. In total, 9 microsatellites and one mitochondrial marker were used to genotyped 433 individuals from 22 different populations. Nuclear DNA and Mitochondrial DNA analysis were carried out to comprehend the effects of historical and contemporary effects on species distribution and range shifts. At a large scale, the analysis shows that Macrocystis pyrifera is subdivided into four main genetic clusters, one in the Magallean region, two in the Falkland Islands, and one in South Africa. Furthermore, populations in the Magallean region have displayed a low genetic diversity that can be linked to recent colonization events while around the Falklands a higher genetic diversity have been found that may reflect historical events. The role played by the Falkland Islands as a refugia for this species is well supported by the phylogeographic structure. Genetic analysis revealed that the distribution around the Falklands has been shaped by contemporary and historical events. Multiple genetic breaks have been observed and are concordant with biogeographic and oceanographic breaks. The present genetic structure can be best explained by transportation through ocean currents and habitat continuity for stepping-stone migration rather than by geographical distance. Kelps are under increasing anthropogenic pressure and environmental changes and unlike most other marine species they can be easily monitored. Thus, further studies need to be carried out to highlight more biogeographic and phylogeographic breaks at a global scale to understand the ecological and evolutionary processes that shape the distribution of kelps. In consequence, it will provide more information for management and conservation policies to be taken.Foi determinada a estrutura genética de Macrocystis pyrifera em torno das Ilhas Malvinas e da região de Magalhães. M. pyrifera, comummente chamada de alga gigante, forma extensas florestas submarinas e como a alga mais amplamente distribuída na terra. Os indivíduos podem crescer até 40 a 50 m de comprimento e é descrito como o organismo bentónico mais alto. De facto, a M.pyrifera é agora definida como uma espécie de fundação, na medida em que desempenha um forte papel na estruturação da comunidade, criando uma estrutura espacial complexa em 3D, influenciando as condições físicas e químicas, e a complexidade dos processos dos ecossistemas. M. pyrifera é também considerada como um engenheiro de ecossistemas na medida em que fornece alimento, habitat e substrato de desova a numerosas espécies, tais como mamíferos, peixes, caranguejos, ouriços do mar, moluscos, epífitos e comunidades bacterianas. Através deste complexo ecossistema estruturado, as florestas de algas não só ampliam a produção secundária e primária, como também apoiam uma diversificada teia alimentar costeira. Macrocystis pyrifera está distribuída ao longo de uma gama latitudinal e longitudinal muito ampla, do Alasca ao México no hemisfério norte, e ao longo da costa sudeste da América do Sul, do Peru à Argentina, mas também, em locais dispersos como a África do Sul, Tasmânia, e várias regiões sub-Antárcticas. Esta ampla gama distributiva mostra a eficiência da aclimatação de Macrocystis para lidar com tal painel de factores ambientais como, temperatura, salinidade, profundidade, luz, nutrientes, e exposição a ondas. Os atributos biológicos, morfologia interna e externa, e traços de história de vida são particularmente relevantes para a ecologia das algas, a fim de compreender como os Macrocystis interagem e lidam com o seu ambiente. A está entre as algas marinhas castanhas mais desenvolvidas, mostrando uma morfologia interna e externa muito complexa na qual cada parte da planta tem de ser capaz de funcionar e lidar com o ambiente que pode ser extremamente variável ao longo do tempo e da profundidade. Os factores bióticos limitam a capacidade de dispersão desta espécie. As literaturas sugerem que a capacidade de dispersão a longa distância é restrita e raramente eficiente. Contudo, estudos recentes têm demonstrado o valioso papel das balsas de algas e dos adultos flutuantes em termos de dispersão a longa distância. Além disso, as jangadas flutuantes demonstraram não só uma elevada capacidade de sobrevivência, aproximadamente 100 dias para alguns indivíduos, mas também o potencial de percorrer centenas de quilómetros enquanto continuam a ser férteis. A alga gigante habita manchas rochosas e tem uma capacidade de dispersão limitada, mas um elevado potencial de dispersão. Parece que a dispersão de longas distâncias por jangadas de algas permite uma fixação eficiente em novo habitat. Assim, pensa-se que a conectividade entre as populações é principalmente impulsionada pelas correntes oceânicas. As Ilhas Malvinas, também chamadas Islas Malvinas, estão localizadas no hemisfério sul, na faixa de vento ocidental na zona temperada a frio sul e situam-se a norte da frente polar, 450 km a nordeste da Terra do Fogo entre a latitude (51-53°S) e longitude (57-61°W) no Atlântico Sul. As Malvinas fornecem um habitat de reprodução essencial para muitas aves marinhas, mamíferos marinhos e espécies de aves costeiras, podendo assim ser caracterizadas como um importante ponto de atracção da biodiversidade. Alguns estudos identificaram 57 espécies de aves marinhas, incluindo 17 espécies de pinguins e 17 espécies de mamíferos marinhos, contudo, para a maioria das espécies foi observada uma variação interanual. A plataforma patagónica de águas pouco profundas produz com as duas correntes uma região de afloramento, o que significa uma água muito rica em nutrientes na origem de um copioso local de alimentação. Foram avaliadas descontinuidades genéticas relacionadas com quebras biogeográficas e o papel de preditores como a continuidade do habitat, dispersão, correntes oceanográficas e batimetria, para compreender a estrutura da metapopulação em redor das Malvinas. No total, 9 microsatélites e um marcador mitocondrial foram utilizados para genotipular 433 indivíduos de 22 populações diferentes. As populações de Macrocystis pyrifera foram amostradas de 2018 a 2019 a partir de cinco sítios na região de Magallean, localizados na Patagónia chilena, de um sítio na África do Sul e de 16 sítios em redor das Ilhas Malvinas (latitude -51,563412 e longitude -59,820557). Foram realizadas análises de ADN nuclear e de ADN mitocondrial para compreender os efeitos dos efeitos históricos e contemporâneos na distribuição das espécies e nas mudanças de distribuição. Em grande escala, a análise mostra que Macrocystis pyrifera está subdividida em quatro grupos genéticos principais, um na região de Magalhães, dois nas Ilhas Malvinas, e um na África do Sul. Além disso, as populações na região de Magallean demonstraram uma baixa diversidade genética que pode ser ligada aos recentes eventos de colonização, enquanto que em redor das Malvinas foi encontrada uma maior diversidade genética que pode reflectir eventos históricos. O papel desempenhado pelas Ilhas Malvinas como refúgio para esta espécie é bem suportado pela estrutura filogeográfica. A análise genética revelou que a distribuição em torno das Malvinas foi moldada por acontecimentos contemporâneos e históricos. Múltiplas quebras genéticas foram observadas e são concordantes com quebras biogeográficas e oceanográficas. A estrutura genética actual pode ser melhor explicada pelo transporte através das correntes oceânicas e pela continuidade do habitat para a migração das estepes, e não pela distância geográfica. As algas estão sob pressão antropogénica crescente e alterações ambientais e, ao contrário da maioria das outras espécies marinhas, podem ser facilmente monitorizadas. A alga gigante é um bom modelo para explorar os efeitos da distribuição espacial no padrão de conectividade devido à sua vasta gama de tamanhos de manchas, distribuição e distâncias que as separam. Os padrões espaciais de diversidade genética são essenciais para determinar os mecanismos evolutivos que conduzem a esta diferenciação genética, tanto quanto para compreender as consequências ecológicas da perda da diversidade genética. A Macrocystis é uma das algas marinhas mais importantes ecológica e economicamente do hemisfério sul. As políticas de gestão e conservação devem ser aplicadas para conservar as florestas de M. pyrifera e espécies ameaçadas, na medida em que aumentará a biodiversidade. Assim, é necessário realizar mais estudos para destacar mais quebras biogeográficas e filogeográficas à escala global, a fim de compreender os processos ecológicos e evolutivos que moldam a distribuição das algas. Em consequência, fornecerá mais informação para as políticas de gestão e conservação a serem tomadas

    Could an endoneurial endothelial crosstalk between Wnt/β-catenin and Sonic Hedgehog pathways underlie the early disruption of the infra-orbital blood-nerve barrier following chronic constriction injury?

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    BackgroundBlood–nerve barrier disruption is pivotal in the development of neuroinflammation, peripheral sensitization, and neuropathic pain after peripheral nerve injury. Activation of toll-like receptor 4 and inactivation of Sonic Hedgehog signaling pathways within the endoneurial endothelial cells are key events, resulting in the infiltration of harmful molecules and immunocytes within the nerve parenchyma. However, we showed in a previous study that preemptive inactivation of toll-like receptor 4 signaling or sustained activation of Sonic Hedgehog signaling did not prevent the local alterations observed following peripheral nerve injury, suggesting the implication of another signaling pathway.MethodsUsing a classical neuropathic pain model, the infraorbital nerve chronic constriction injury (IoN-CCI), we investigated the role of the Wnt/β-catenin pathway in chronic constriction injury-mediated blood–nerve barrier disruption and in its interactions with the toll-like receptor 4 and Sonic Hedgehog pathways. In the IoN-CCI model versus control, mRNA expression levels and/or immunochemical detection of major Wnt/Sonic Hedgehog pathway (Frizzled-7, vascular endothelial-cadherin, Patched-1 and Gli-1) and/or tight junction proteins (Claudin-1, Claudin-5, and Occludin) readouts were assessed. Vascular permeability was assessed by sodium fluorescein extravasation.ResultsIoN-CCI induced early alterations in the vascular endothelial-cadherin/β-catenin/Frizzled-7 complex, shown to participate in local blood–nerve barrier disruption via a β-catenin-dependent tight junction protein downregulation. Wnt pathway also mediated a crosstalk between toll-like receptor 4 and Sonic Hedgehog signaling within endoneurial endothelial cells. Nevertheless, preemptive inhibition of Wnt/β-catenin signaling before IoN-CCI could not prevent the downregulation of key Sonic Hedgehog pathway readouts or the disruption of the infraorbital blood–nerve barrier, suggesting that Sonic Hedgehog pathway inhibition observed following IoN-CCI is an independent event responsible for blood–nerve barrier disruption.ConclusionA crosstalk between Wnt/β-catenin- and Sonic Hedgehog-mediated signaling pathways within endoneurial endothelial cells could mediate the chronic disruption of the blood–nerve barrier following IoN-CCI, resulting in increased irreversible endoneurial vascular permeability and neuropathic pain development

    Endothéline-1, angiotensine II et cancer

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    L’endothéline-1 (ET-1) et l’angiotensine II (AngII) sont des peptides vasoactifs, mais aussi mitogènes et pro-angiogéniques. Tous deux exercent leurs actions par l’intermédiaire de récepteurs couplés aux protéines G : ETA-R et ETB-R pour ET-1 ; AT1R et AT2R pour AngII. L’expression des composants des systèmes ET-1 et AngII dans diverses tumeurs présente généralement une ou plusieurs des caractéristiques suivantes : surexpression du peptide et/ou du récepteur, modification du sous-type de récepteur exprimé et localisation nucléaire du récepteur. ET-1 et AngII agissent sur les différentes étapes de la progression tumorale, et l’utilisation d’antagonistes spécifiques de leurs récepteurs, ou d’inhibiteurs de leur synthèse, est efficace pour ralentir la croissance tumorale in vitro et in vivo dans différents modèles animaux. Des essais cliniques utilisant des antagonistes d’ETA-R donnent des résultats encourageants pour le traitement antitumoral, et une approche similaire ayant pour objectif de bloquer ETB-R ou AT1R est envisageable. De plus, une thérapie combinée ciblant les deux systèmes, ET-1 et AngII, pourrait se révéler bénéfique pour le traitement de tumeurs fortement angiogéniques.Endothelin-1 (ET-1) and angiotensin II (AngII), two potent vasoactive peptides involved in the regulation of cardiovascular homeostasis, also induce mitogenic and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme and angiotensin-converting enzyme, respectively) and activate two subtypes of membrane receptors (ETA-R and ETB-R for ET-1, AT1R and AT2R for AngII) that all belong to the superfamily of G-protein coupled receptors. There is increasing evidence that ETA-R, ETB-R and AT1R are expressed in a variety of cancer cells and tissues, and may play a role on tumor growth, angiogenesis and invasion in vivo. This review summarizes the similarities and differences between the ET-1 and AngII systems with regard to their reported effects on various aspects of cancer. In addition to being expressed on vascular endothelium, ET-1 and AngII receptors participate in tumor angiogenesis through the production of the angiogenic factor VEGF. Furthermore, recent clinical studies indicate that a selective ETA-R antagonist has beneficial effects in prostate cancer, suggesting that a similar approach using ETB-R and AT1R blockers might be envisioned. Experimental data presented here suggest that a combined therapy targeting both ET-1 and AngII systems may prove valuable for future treatments of highly angiogenic tumors

    Le cancer broncho-pulmonaire du non-fumeur : un modèle pour le diagnostic non-invasif des biomarqueurs tumoraux et l'évaluation de leurs interactions avec l'exposition aux facteurs de risque

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    Lung cancer in never smokers (LCINS) is considered as a separate entity given its epidemiological specificities. It is also a very interesting template to assess alternative risk factors for lung cancers than tobacco smoking. However, there is very little non-Asian data about this particular topic. The BioCAST / IFCT1002 study is a prospective, nationwide, and multi-centric epidemiological study. Its main objective was to describe a French population of lung cancers in lifelong never smokers (less than 100 cigarette during all lifetime); with a special focus on molecular somatic profile and risk-factors exposure. Secondary objectives were to assess the interaction between risk-factor exposure and molecular profile; and to use this particular cohort to develop a multiplex test for non-invasive diagnosis of tumor mutations in circulating free DNA. Overall, 384 patients were recruited in the cohort. Two-third were exposed to passive smoking (mainly women and in domestic setting). By contrast, 35% of men were definitely exposed to occupational carcinogens versus 8% of women. Finally, 72% were found with a somatic mutation, mainly in the EGFR gene (51% of the whole population). Gender or exposure to risk factors such as passive smoking, occupational exposure, or hormonal status in women, were not significantly associated with a specific and/or clinically meaningful molecular profile in tumor. These findings should be interpreted with caution given that some subgroups were small and/or with many simultaneous exposures. However, exposure to asbestos and/or silica was significantly associated to a decreased risk for EGFR mutation. On the pilot study (n=106), circulating free DNA was associated with tumor burden. The multiplex diagnosis (12 amplicons on 5 genes) by next-generation sequencing was feasible and gave encouraging results in stage 4 patients (67% sensitivity, 73% concordance rate). LCINS is an interesting entity for the study of non-tobacco-related cancer risk factors; or to optimize liquid biopsy strategyLe cancer broncho-pulmonaire du non-fumeur est considéré comme une entité à part du fait de ses particularités épidémiologiques. Il est en outre un excellent modèle pour l'étude des facteurs de risque de cancer bronchique autres que le tabagisme actif. Il n'existe que très peu de données non-asiatiques concernant cette entité d'intérêt. Le bio-observatoire national des cancers bronchiques de non-fumeurs (BioCAST I IFCT-1002) est une étude épidémiologique multicentrique prospective. Son objectif principal est de décrire une population de patient strictement non-fumeur (moins de 100 cigarettes au cours de la vie) atteint de cancer bronchique, notamment sur le plan de leur profil moléculaire somatique et de leur exposition aux facteurs de risque. Les objectifs secondaires étaient d'étudier si l'exposition aux différents facteurs de risque pouvait influencer le profil moléculaire ; et d'utiliser cette cohorte particulière (grande fréquence et diversité de mutations somatiques attendue) afin de développer un test multiplex pour le diagnostic non-invasif du profil moléculaire somatique tumoral à partir d'ADN circulant. Au total, 384 patients non-fumeurs atteints de cancer broncho-pulmonaire ont été inclus dans cette cohorte. Deux-tiers d'entre eux étaient exposés au tabagisme passif, et il s'agissait essentiellement d'une exposition domestique touchant les femmes. Inversement, 35% des hommes étaient exposés de manière certaine à au moins un cancérogène professionnel, contre 8% des femmes. Au total, 72% des patients présentait une anomalie moléculaire, essentiellement au niveau de l'EGFR (51% de l'ensemble de la cohorte). Le genre, ou l'exposition à différents facteurs de risque (tabagisme passif, exposition professionnelle, exposition hormonale chez les femmes) n'affectait pas de manière significative et cliniquement pertinente le profil mutationnel, avec les limites liée à de faibles effectifs dans certains groupes et aux expositions multiples. Seule l'exposition professionnelle à l'amiante et / ou à la silice semble avoir pour effet de diminuer la fréquence des mutations de l'EGF

    The Brain Microvascular Endothelium Supports T Cell Proliferation and Has Potential for Alloantigen Presentation

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    Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4+ and CD8+ T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases. © 2013 Wheway et al

    The blood-brain barrier in brain homeostasis and neurological diseases

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    AbstractBrain endothelial cells are unique among endothelial cells in that they express apical junctional complexes, including tight junctions, which quite resemble epithelial tight junctions both structurally and functionally. They form the blood-brain-barrier (BBB) which strictly controls the exchanges between the blood and the brain compartments by limiting passive diffusion of blood-borne solutes while actively transporting nutrients to the brain. Accumulating experimental and clinical evidence indicate that BBB dysfunctions are associated with a number of serious CNS diseases with important social impacts, such as multiple sclerosis, stroke, brain tumors, epilepsy or Alzheimer's disease. This review will focus on the implication of brain endothelial tight junctions in BBB architecture and physiology, will discuss the consequences of BBB dysfunction in these CNS diseases and will present some therapeutic strategies for drug delivery to the brain across the BBB

    Uptake and cytotoxicity of citrate-coated gold nanospheres : comparative studies on human endothelial and epithelial cells

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    The use of gold nanoparticles (AuNPs) for diagnostic applications and for drug and gene-delivery is currently under intensive investigation. For such applications, biocompatibility and the absence of cytotoxicity of AuNPs is essential. Although generally considered as highly biocompatible, previous in vitro studies have shown that cytotoxicity of AuNPs in certain human epithelial cells was observed. In particular, the degree of purification of AuNPs (presence of sodium citrate residues on the particles) was shown to affect the proliferation and induce cytotoxicity in these cells. To expand these studies, we have examined if the effects are related to nanoparticle size (10, 11 nm, 25 nm), to the presence of sodium citrate on the particles' surface or they are due to a varying degree of internalization of the AuNPs. Since two cell types are present in the major barriers to the outside in the human body, we have also included endothelial cells from the vasculature and blood brain barrier. Results Transmission electron microscopy demonstrates that the internalized gold nanoparticles are located within vesicles. Increased cytotoxicity was observed after exposure to AuNPs and was found to be concentration-dependent. In addition, cell viability and the proliferation of both endothelial cells decreased after exposure to gold nanoparticles, especially at high concentrations. Moreover, in contrast to the size of the particles (10 nm, 11 nm, 25 nm), the presence of sodium citrate on the nanoparticle surface appeared to enhance these effects. The effects on microvascular endothelial cells from blood vessels were slightly enhanced compared to the effects on brain-derived endothelial cells. A quantification of AuNPs within cells by ICP-AES showed that epithelial cells internalized a higher quantity of AuNPs compared to endothelial cells and that the quantity of uptake is not correlated with the amount of sodium citrate on the nanoparticles’ surface. Conclusions In conclusion the higher amount of citrate on the particle surface resulted in a higher impairment of cell viability, but did not enhance or reduce the uptake behavior in endothelial or epithelial cells. In addition, epithelial and endothelial cells exhibited different uptake behaviors for citrate-stabilized gold nanoparticles, which might be related to different interactions occurring at the nanoparticle-cell-surface interface. The different uptake in epithelial cells might explain the higher reduction of proliferation of these cells after exposure to AuNPs treatment although more detailed investigations are necessary to determine subcellular events. Nevertheless an extrinsic effect of sodium-citrate stabilized particles could not be excluded. Thus, the amount of sodium citrate should be reduced to a level on which the stability of the particles and the safety for biomedical applications are guaranteed

    Risk Perception in Online Communities

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    Online communities have become a part of everyday life for many people. The members of the communities use them to keep in touch with family and friends, do business, look for jobs, play games, and more, both savory and unsavory. The ease of sharing personal information comes with the subsequent risk of having that information exposed publically or even stolen. The purpose of this study was to explore how much awareness of the risks affects a person’s decision to post personal information to an online community. Chapter I introduces the concepts and issues that will be investigated by this paper. Chapter II is a review of the literature on risk. Chapter III explains the model that was developed and used determine the relationships between risk perception, attitude, fear, and information revelation. Chapter IV explains the methods used to gather the data and what data was gathered. Chapter V contains the analysis of the data collected. Chapter VI contains the conclusion drawn from the data, implications for the research, and directions for future research
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