2,448 research outputs found

    Mis-Specification and Frequency Dependence in a New Keynesian Phillips Curve

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    Phillips Curve, spectral regression, time series analysis

    Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain

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    Background: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. Results: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1 angstrom resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. Conclusion: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.Publisher PDFPeer reviewe

    Adjustment and Sensitivity Analyses of a Beta Global Rangeland Model

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    G-Range is a global model that simulates generalized changes in rangelands through time, created with support from the International Livestock Research Institute. Spatial data and a set of parameters that control plant growth and other ecological attributes in landscape units combine with computer code to represent ecological process such as soil nutrient and water dynamics, vegetation growth, fire, and wild and domestic animal offtake. The model is spatial, with areas of the world divided into square cells

    Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain

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    <p>Abstract</p> <p>Background</p> <p>IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region.</p> <p>Results</p> <p>The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1Å resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs.</p> <p>Conclusion</p> <p>The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.</p

    The Value of Bt Corn in Southwest Kansas: A Monte Carlo Simulation Approach

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    While most Corn Belt farmers consider planting Bt corn to control European corn borer, southwestern Kansas farmers must also take into account an array of other insect pests, including corn rootworm, spider mites, and southwestern corn borer. This research uses a decision analysis framework to estimate the expected economic value of Bt corn in southwest Kansas. Mean per acre Bt values ranged from 12.49to12.49 to 34.60, well above the technology fee assumed to be 14perunit,or14 per unit, or 5.25 per acre at a seeding rate of 30,000 seeds per acre. The minimum value over all scenarios was $8.69 per acre. Using Monte Carlo simulation, it was shown that European and southwestern corn borer infestation probabilities, expected corn price, and expected pest-free yields are important determinants of the value of Bt corn.Bt corn, decision analysis, European corn borer, integrated pest management, Monte Carlo simulation, southwestern corn borer, Crop Production/Industries,

    Using Decision Analysis to Improve Malaria Control Policy Making

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    Malaria and other vector-borne diseases represent a significant and growing burden in many tropical countries. Successfully addressing these threats will require policies that expand access to and use of existing control methods, such as insecticide-treated bed nets (ITNs) and artemesinin combination therapies (ACTs) for malaria, while weighing the costs and benefits of alternative approaches over time. This paper argues that decision analysis provides a valuable framework for formulating such policies and combating the emergence and re-emergence of malaria and other diseases. We outline five challenges that policy makers and practitioners face in the struggle against malaria, and demonstrate how decision analysis can help to address and overcome these challenges. A prototype decision analysis framework for malaria control in Tanzania is presented, highlighting the key components that a decision support tool should include. Developing and applying such a framework can promote stronger and more effective linkages between research and policy, ultimately helping to reduce the burden of malaria and other vector-borne diseases
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