357 research outputs found

    Interleukin-1β Produced in Response to Islet Autoantigen Presentation Differentiates T-Helper 17 Cells at the Expense of Regulatory T-Cells: Implications for the Timing of Tolerizing Immunotherapy

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    OBJECTIVE-The effectiveness of tolerizing immunotherapeutic strategies, such as anti-CD40L or dendritic cells (DCs), is greater when administered to young nonobese diabetic (NOD) mice than at peak insulitis. RelB(lo) DCs, generated in the presence of an nuclear factor-kappa B inhibitor, induce T-regulatory (Treg) cells and suppress inflammation in a model of rheumatoid arthritis. Interleukin (IL)-1 beta is overexpressed in humans and mice at risk of type 1 diabetes, dysregulates Treg cells, and accelerates diabetes in NOD mice. We investigated the relationship between IL-1 beta production and the response to RelB(lo) DCs in the prediabetic period

    Understanding the role of eco-evolutionary feedbacks in host-parasite coevolution

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    It is widely recognised that eco-evolutionary feedbacks can have important implications for evolution. However, many models of host-parasite coevolution omit eco-evolutionary feedbacks for the sake of simplicity, typically by assuming the population sizes of both species are constant. It is often difficult to determine whether the results of these models are qualitatively robust if eco-evolutionary feedbacks are included. Here, by allowing interspecific encounter probabilities to depend on population densities without otherwise varying the structure of the models, we provide a simple method that can test whether eco-evolutionary feedbacks per se affect evolutionary outcomes. Applying this approach to explicit genetic and quantitative trait models from the literature, our framework shows that qualitative changes to the outcome can be directly attributable to eco-evolutionary feedbacks. For example, shifting the dynamics between stable monomorphism or polymorphism and cycling, as well as changing the nature of the cycles. Our approach, which can be readily applied to many different models of host-parasite coevolution, offers a straightforward method for testing whether eco-evolutionary feedbacks qualitatively change coevolutionary outcomes

    Understanding delay in developmental disorders

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    Researchers in developmental disorders frequently refer to abilities that are in line with mental age as simply delayed. The qualifier simply might imply an existing theory of developmental delay that is well understood and uninteresting (perhaps because it is an exaggerated form of individual differences, the responsibility of other researchers). In this article, I argue that the notion of delay can be separated into descriptive and explanatory versions. The descriptive version is often used too coarsely to be helpful. Instead, we need an approach based on developmental trajectories to separate types of descriptive delay, which may then have different underlying causes. The explanatory version is poorly articulated in developmental theory. One useful way to deepen our understanding of delay is by building computational models that simulate development in large populations of individuals and explicitly implementing factors that cause variations in development. Finally, I suggest that dividing research among separate investigators of typical development, individual differences, and developmental disorders may be counterproductive if the underlying mechanisms recognize no such distinction

    Measurement of the Non-Common Vertex Error of a Double Corner Cube

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    ABSTRACT The Space Interferometry Mission (SIM) requires the control of the optical path of each interferometer with picometer accuracy. Laser metrology gauges are used to measure the path lengths to the fiiducial corner cubes at the siderostats. Due to the geometry of SIM a single corner cube does not have sufficient acceptance angle to work with all the gauges. Therefore SIM employs a double corner cube. Current fabrication methods are in fact not capable of producing such a double corner cube with vertices having sufficient commonality. The plan for SIM is to measure the non-commonalty of the vertices and correct for the error in orbit. SIM requires that the non-common vertex error (NCVE) of the double corner cube to be less than 6 µm. The required accuracy for the knowledge of the NCVE is less than 1 µm. This paper explains a method of measuring non-common vertices of a brassboard double corner cube with sub-micron accuracy. The results of such a measurement will be presented

    Multi-mode fluctuating selection in host-parasite coevolution

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    Published onlineLetterThis is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Understanding fluctuating selection is important for our understanding of patterns of spatial and temporal diversity in nature. Host-parasite theory has classically assumed fluctuations either occur between highly specific genotypes (matching allele: MA) or from specialism to generalism (gene-for-gene: GFG). However, while MA can only generate one mode of fluctuating selection, we show that GFG can in fact produce both rapid 'within-range' fluctuations (among genotypes with identical levels of investment but which specialise on different subsets of the population) and slower cycling 'between ranges' (different levels of investment), emphasising that MA is a subset of GFG. Our findings closely match empirical observations, although sampling rates need to be high to detect these novel dynamics empirically. Within-range cycling is an overlooked process by which fluctuating selection can occur in nature, suggesting that fluctuating selection may be a more common and important process than previously thought in generating and maintaining diversity.This work was supported by the Natural Environment Research Council (NE/N014979/1 and NE/K014617/1)
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