2,316 research outputs found
TIM-4 is a critical EBOV receptor on peritoneal macrophages.
No full textA) TIM-4 surface expression. Matured bone marrow derived macrophages and pmacs from C57BL/6 Ifnar-/- mice were lifted from tissue culture plates, stained with directly conjugated F4/80 and CD11b mAb. Positively gated cells were analyzed for TIM-4 (grey histogram) or isotype control (white histogram) by flow cytometry. B) TIM-4 expression is required for robust rVSV/EBOV GP infection. C57BL/6 Ifnar-/- or Ifnar/Timd-4 -/- pmacs were infected with the indicated infectious units of rVSV/EBOV GP. Twenty-four hours following infection, cells were quantified for GFP expression by flow cytometry. C) Infection of BMDMs is not affected by the absence of TIM-4 expression. Bone marrow cells were isolated from C57BL/6 Ifnar-/- or Ifnar/Timd-4 -/- mice. Adherent cells were matured into macrophages by incubating for 6 days in the presence of 50ng/mL MCSF. Matured macrophages were infected with the indicated infectious units of rVSV/EBOV GP and number of infected cells were quantified by GFP expression at 24 hour following infection by flow cytometry. D) Pmacs were harvested from C57BL/6 Ifnar-/- or Ifnar/Timd-4 -/- mice and incubated with VLPs expressing EBOV GP and EBOV VP40 fused to beta lactamase. Virus/cell membrane fusion was subsequently quantified by loading cells with CCF2-AM, a β-lactam-containing fluorescent substrate, and analyzed on flow cytometry to determine the relative amount of cleaved and un-cleaved substrate. Data are shown as mean ± S.D. Statistics were calculated using Student’s t-test, *p<0.05.</p
TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis
No full textBackgroundT cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection.Methodology/Principal findingsInfectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection.ConclusionsOur studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection.</div
What to bid and when to stop
No full textNegotiation is an important activity in human society, and is studied by various disciplines, ranging from economics and game theory, to electronic commerce, social psychology, and artificial intelligence. Traditionally, negotiation is a necessary, but also time-consuming and expensive activity. Therefore, in the last decades there has been a large interest in the automation of negotiation, for example in the setting of e-commerce. This interest is fueled by the promise of automated agents eventually being able to negotiate on behalf of human negotiators.Every year, automated negotiation agents are improving in various ways, and there is now a large body of negotiation strategies available, all with their unique strengths and weaknesses. For example, some agents are able to predict the opponent's preferences very well, while others focus more on having a sophisticated bidding strategy. The problem however, is that there is little incremental improvement in agent design, as the agents are tested in varying negotiation settings, using a diverse set of performance measures. This makes it very difficult to meaningfully compare the agents, let alone their underlying techniques. As a result, we lack a reliable way to pinpoint the most effective components in a negotiating agent.There are two major advantages of distinguishing between the different components of a negotiating agent's strategy: first, it allows the study of the behavior and performance of the components in isolation. For example, it becomes possible to compare the preference learning component of all agents, and to identify the best among them. Second, we can proceed to mix and match different components to create new negotiation strategies., e.g.: replacing the preference learning technique of an agent and then examining whether this makes a difference. Such a procedure enables us to combine the individual components to systematically explore the space of possible negotiation strategies.To develop a compositional approach to evaluate and combine the components, we identify structure in most agent designs by introducing the BOA architecture, in which we can develop and integrate the different components of a negotiating agent. We identify three main components of a general negotiation strategy; namely a bidding strategy (B), possibly an opponent model (O), and an acceptance strategy (A). The bidding strategy considers what concessions it deems appropriate given its own preferences, and takes the opponent into account by using an opponent model. The acceptance strategy decides whether offers proposed by the opponent should be accepted.The BOA architecture is integrated into a generic negotiation environment called Genius, which is a software environment for designing and evaluating negotiation strategies. To explore the negotiation strategy space of the negotiation research community, we amend the Genius repository with various existing agents and scenarios from literature. Additionally, we organize a yearly international negotiation competition (ANAC) to harvest even more strategies and scenarios. ANAC also acts as an evaluation tool for negotiation strategies, and encourages the design of negotiation strategies and scenarios.We re-implement agents from literature and ANAC and decouple them to fit into the BOA architecture without introducing any changes in their behavior. For each of the three components, we manage to find and analyze the best ones for specific cases, as described below. We show that the BOA framework leads to significant improvements in agent design by wining ANAC 2013, which had 19 participating teams from 8 international institutions, with an agent that is designed using the BOA framework and is informed by a preliminary analysis of the different components.In every negotiation, one of the negotiating parties must accept an offer to reach an agreement. Therefore, it is important that a negotiator employs a proficient mechanism to decide under which conditions to accept. When contemplating whether to accept an offer, the agent is faced with the acceptance dilemma: accepting the offer may be suboptimal, as better offers may still be presented before time runs out. On the other hand, accepting too late may prevent an agreement from being reached, resulting in a break off with no gain for either party. We classify and compare state-of-the-art generic acceptance conditions. We propose new acceptance strategies and we demonstrate that they outperform the other conditions. We also provide insight into why some conditions work better than others and investigate correlations between the properties of the negotiation scenario and the efficacy of acceptance conditions.Later, we adopt a more principled approach by applying optimal stopping theory to calculate the optimal decision on the acceptance of an offer. We approach the decision of whether to accept as a sequential decision problem, by modeling the bids received as a stochastic process. We determine the optimal acceptance policies for particular opponent classes and we present an approach to estimate the expected range of offers when the type of opponent is unknown. We show that the proposed approach is able to find the optimal time to accept, and improves upon all existing acceptance strategies.Another principal component of a negotiating agent's strategy is its ability to take the opponent's preferences into account. The quality of an opponent model can be measured in two different ways. One is to use the agent's performance as a benchmark for the model's quality. We evaluate and compare the performance of a selection of state-of-the-art opponent modeling techniques in negotiation. We provide an overview of the factors influencing the quality of a model and we analyze how the performance of opponent models depends on the negotiation setting. We identify a class of simple and surprisingly effective opponent modeling techniques that did not receive much previous attention in literature.The other way to measure the quality of an opponent model is to directly evaluate its accuracy by using similarity measures. We review all methods to measure the accuracy of an opponent model and we then analyze how changes in accuracy translate into performance differences. Moreover, we pinpoint the best predictors for good performance. This leads to new insights concerning how to construct an opponent model, and what we need to measure when optimizing performance.Finally, we take two different approaches to gain more insight into effective bidding strategies. We present a new classification method for negotiation strategies, based on their pattern of concession making against different kinds of opponents. We apply this technique to classify some well-known negotiating strategies, and we formulate guidelines on how agents should bid in order to be successful, which gives insight into the bidding strategy space of negotiating agents. Furthermore, we apply optimal stopping theory again, this time to find the concessions that maximize utility for the bidder against particular opponents. We show there is an interesting connection between optimal bidding and optimal acceptance strategies, in the sense that they are mirrored versions of each other.Lastly, after analyzing all components separately, we put the pieces back together again. We take all BOA components accumulated so far, including the best ones, and combine them all together to explore the space of negotiation strategies.We compute the contribution of each component to the overall negotiation result, and we study the interaction between components. We find that combining the best agent components indeed makes the strongest agents. This shows that the component-based view of the BOA architecture not only provides a useful basis for developing negotiating agents but also provides a useful analytical tool. By varying the BOA components we are able to demonstrate the contribution of each component to the negotiation result, and thus analyze the significance of each. The bidding strategy is by far the most important to consider, followed by the acceptance conditions and finally followed by the opponent model.Our results validate the analytical approach of the BOA framework to first optimize the individual components, and then to recombine them into a negotiating agent
Henri Lefebvre, Space and Folklore
No full textNous explorons la pensée complexe d’Henri Lefebvre concernant l’espace, ainsi que ses implications pour les ethnologues, au moyen d’une conversation fictive entre Lefebvre et l’auteur de cet article, au cours d’une promenade dans une petite ferme du sud-est de la Colombie britannique. Certains aspects des points de vue de Lefebvre sont exposés et illustrés à partir d’exemples se présentant sur place, tels que des clôtures ou des emplacements de feux de camp. Le schéma tripartite de Lefebvre pour conceptualiser l’espace s’articule dans le cours de la conversation, en mettant en avant l’importance du concept souvent éludé d’« espace vécu ». Nous voulons démontrer que considérer l’espace de cette manière dialogique, inclusive et ouverte, amènerait à une régénération et à une approche potentiellement transformative de notre compréhension de l’espace — une approche qui aurait de nombreuses implications dans l’étude des traditions culturelles.The complex spatial thinking of Henri Lefebvre and its implications for folkloristics are explored in the context of a fictitious conversation between him and the author as they walk around a small farm in southeastern British Columbia. Aspects of Lefebvre’s position are explored and illustrated using examples from this setting, such as fences and campfire pits. Lefebvre’s tripartite schema for conceptualizing space is articulated during this conversation, foregrounding the importance of the oft-occluded espace vécu (lived space). Viewing this as a dialogic, embodied, open-ended domain of space is shown to be a highly generative and potentially transformative approach to understanding space — an approach which has numerous implications for the study of cultural tradition
Literature-informed, one-turn action research: three cases and a commentary
No full textAlthough action research is a common feature of courses of initial teacher training, the evidence as to its efficacy, in encouraging reflection among trainees, is mixed. This article discusses cases of action research assignments carried out by three trainees into their own practice in relation to a) behaviour management, b) monitoring and assessing, and c) pupil-centred education. The assignments are analysed using Bloom’s (1964) typology of thinking skills, Handal & Lauvas’ (1987) model of reflective practice, and typologies of action research by Noffke (1997) and Rearick & Feldman (1999). They are positioned as cases of ‘literature-informed, one-turn’ action research; a concept which is discussed in relation to other concepts of action research
Loss of TIM-1 reduces mortality following EBOV GP/rVSV and EBOV GP ΔO/rVSV infection, but not G/rVSV.
No full textA and B. Female BALB/c Ifnar-/- (control) and BALB/c Ifnar -/-/TIM-1-/- (TIM-1-/-) mice infected with 105 iu EBOV GP/rVSV (A; n = 5 mice per group) or EBOV GP ΔO/rVSV (B; n = 13–17 mice per group) by intravenous (i.v.) injection. C. Female BALB/c Ifnar -/- (control) and BALB/c Ifnar -/-/TIM-1-/- (TIM-1-/-) mice infected with 105 iu G/rVSV (n = 10 mice per group) by i.v. infection. D. Similar G/rVSV challenge studies as shown in panel C, but mice were challenged with 101 iu (n = 5 mice per group) of G/rVSV. Survival was assessed following infection for all mouse studies. Significance for survival curve was determined by Log Rank (Mantel-Cox) test, * p< 0.05, **p < 0.01. LT50 = median lethal time until death; NC, noncalculable; ns, not significant.</p
Photon-sail trajectories to exoplanet Proxima b using heteroclinic connections
No full textNow that a rocky planet is confirmed to orbit in the habitable zone of our closest stellar neighbor Proxima Centauri, the interest in visiting that system is growing; especially since Breakthrough Starshot proposed a fly-through mission of the Alpha Centauri system by sending a swarm of laser-driven photon sails. While many engineering problems still need to be solved for such a mission to succeed, research has shown that futuristic, theoretical photon-sail configurations can reach the Alpha Centauri system within 75-80 years while also getting captured in a bound orbit about one of the binary stars. This paper investigates trajectories from the binary star system towards planet Proxima b. A mission to Proxima b is scientifically grounded since measurements or pictures could help us better comprehend the evolution of rocky planets and potential life-formation in our Universe. The classical Lagrange points in the binary system (AC-A/AC-B) and the system Proxima Centauri-Proxima b (AC-C/Proxima b) are used to find possible trajectories towards Proxima b. The transfer is divided into a departure phase from AC-A/AC-B and an arrival phase to AC-C/Proxima b. Heteroclinic connections are then exploited using a patched restricted three-body problem method to connect the two phases. A grid search is applied on the optimization parameters to explore the design space, after which a genetic algorithm is applied to further optimize the link, focusing on minimization of the position, velocity, and time error at linkage. Futuristic sail configurations are used, including double-sided reflective sails and lightness numbers up to ß = 1779. The design space exploration shows that a double-sided sail provides little improvement over a one-sided sail, mainly due to the constant sail attitude along the trajectories. Results from the genetic algorithm show that a transfer from the L2-point in the AC-A/AC-B system to the L1-point in the AC-C/Proxima b can be accomplished with a transfer time of 235 years for the one-sided graphene-based sail with a surface of 315x315 m^2 carrying a payload of 10 grams. A transfer from the L2-point in the AC-A/AC-B system to the L3-point in the AC-C/Proxima b, with a smaller one-sided graphene-based sail (75x75 m^2, carrying a payload of 10 grams), results in a transfer time of 1025 years. For both sail configurations, the position error at linkage is kept below 1% of the total travel distance, the velocity error below 1% of the velocity at linkage, and the time error below 1% of the total transfer time.Aerospace Engineerin
Nostalgia: content, triggers, functions
No full textSeven methodologically diverse studies addressed 3 fundamental questions about nostalgia. Studies 1 and 2 examined the content of nostalgic experiences. Descriptions of nostalgic experiences typically featured the self as a protagonist in interactions with close others (e.g., friends) or in momentous events (e.g., weddings). Also, the descriptions contained more expressions of positive than negative affect and often depicted the redemption of negative life scenes by subsequent triumphs. Studies 3 and 4 examined triggers of nostalgia and revealed that nostalgia occurs in response to negative mood and the discrete affective state of loneliness. Studies 5, 6, and 7 investigated the functional utility of nostalgia and established that nostalgia bolsters social bonds, increases positive self-regard, and generates positive affect. These findings demarcate key landmarks in the hitherto uncharted research domain of nostalgi
Athabasca School District No. 839 (1958-1959)
No full textPhotograph - Teacher Alice B. Donahue and her grade two class at Athabasca Public School, Athabasca, Alberta. Front row: Daryl Goodwin, Howard McLeod, Rick Zelman, ....Budney, unknown, unknown, Brenda Guay, Pat Mackie, Tim King, Alice Kobzey. Middle row: ....Todd, Lyle ..., Frank McCullough, Janice Locker, Gordon Lines, unknown, Linda Harper, unknown, Paul Gustafson, Vernon ...Back row: unknown, Lorna Jewell, Leon Guay, John McLevin, Carol McKelvey, Gordon Loiselle, Kathy Kaplun, unknown, unknow
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