286 research outputs found

    Semiparametric Estimation and Inference in Multinomial Choice Models

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    The purpose of this paper is to incorporate semiparametric alternatives to maximum likelihood estimation and inference in the context of unordered multinomial response data when in practice there is often insufficient information to specify the parametric form of the function linking the observables to the unknown probabilities. We specify the function linking the observables to the unknown probabilities using a very general flexible class of functions belonging to the Pearson system of cumulative distribution equations. In this setting we consider the observations as arising from a multinomial distribution characterized by one of the CDFs in the Pearson system. Given this situation, it is possible to utilize the concept of unbiased estimating functions (EFs), combined with the concept of empirical likelihood (EL) to define an (empirical) likelihood function for the parameter vector based on a nonparametric representation of the sample's PDF. This leads to the concept of maximum empirical likelihood (MEL) estimation and inference, which is analogous to parametric maximum likelihood methods in many respects.Demand and Price Analysis,

    A STRUCTURAL-EQUATION GME ESTIMATOR

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    A generalized maximum entropy estimator is developed for the linear simultaneous equations systems model. We provide results on large and small sample properties of the estimator. Empirical results illustrate efficiency advantages of the generalized maximum entropy estimator proposed in this study over traditional estimators (e.g., 2SLS and 3SLS).Research Methods/ Statistical Methods,

    Looking back and moving forward

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    This chapter brings together the research on teacher resilience and approaches to supporting resilience and wellbeing discussed in this volume. As many of the approaches utilised aspects of the BRiTE and Staying BRiTE projects, I highlight common themes as well as the different ways the authors developed and implemented their work to reflect their specific contexts and participants. I also reflect on broader issues related to conceptualisation of resilience, consider where responsibility for resilience lies, and explore future directions. The chapter also provides some insights regarding the collegial collaboration that has made the body of work possible

    B7-H1-Deficiency Enhances the Potential of Tolerogenic Dendritic Cells by Activating CD1d-Restricted Type II NKT Cells

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    Background: Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4+ T cell and NKT cell responses. Methodology/Principal Findings: Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semimature DC that were generated from bone marrow (BM) cells of B7-H12/2 mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC. Injections of B7-H12/2 TNF-DC induced higher release of peptide-specific IL-10 and IL-13 after restimulation in vitro together with elevated serum cytokines IL-4 and IL-13 produced by NKT cells, and reduced IL-17 and IFN-c production in the CNS. Experiments in CD1d2/2 and Ja2812/2 mice as well as with type I and II NKT cell lines indicated that only type II NKT cells but not type I NKT cells (invariant NKT cells) could be stimulated by an endogenous CD1d-ligand on DC and were responsible for the increased serum cytokine production in the absence of B7-H1. Conclusions/Significance: Together, our data indicate that BM-DC express an endogenous CD1d ligand and B7-H1 to ihibit type II but not type I NKT cells. In the absence of B7-H1 on these DC their tolerogenic potential to stimulate tolerogenic CD4+ and NKT cell responses is enhanced

    Phosphodiesterase 3B Is Localized in Caveolae and Smooth ER in Mouse Hepatocytes and Is Important in the Regulation of Glucose and Lipid Metabolism

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    Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes

    A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

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    <p>Abstract</p> <p>Background</p> <p>The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes.</p> <p>Results</p> <p>To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4<sup>+ </sup>cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, <it>IL7R</it>, was selected for further validation. The expression levels of <it>IL7R </it>in allergen challenged CD4<sup>+ </sup>cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies.</p> <p>Conclusion</p> <p>We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.</p
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