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We introduce a framework for the control of discrete-time switched stochastic systems with uncertain distributions. In particular, we consider stochastic dynamics with additive noise whose distribution lies in an ambiguity set of distributions that are ɛ − close, in the Wasserstein distance sense, to a nominal one. We propose algorithms for the efficient synthesis of distributionally robust control strategies that maximize the satisfaction probability of reach-avoid specifications with either a given or an arbitrary (not specified) time horizon, i.e., unbounded-time reachability. The framework consists of two main steps: finite abstraction and control synthesis. First, we construct a finite abstraction of the switched stochastic system as a robust Markov decision process (robust MDP) that encompasses both the stochasticity of the system and the uncertainty in the noise distribution. Then, we synthesize a strategy that is robust to the distributional uncertainty on the resulting robust MDP. We employ techniques from optimal transport and stochastic programming to reduce the strategy synthesis problem to a set of linear programs, and propose a tailored and efficient algorithm to solve them. The resulting strategies are correctly refined into switching strategies for the original stochastic system. We illustrate the efficacy of our framework on various case studies comprising both linear and non-linear switched stochastic systems. [ABSTRACT FROM AUTHOR]

IgE is the less abundant immunoglobulin isotype in serum and displays higher affinity for its cognate Fc receptor (FcεRI) than the rest of antibody isotypes. Moreover, the class switch recombination and the generation of memory responses remarkably differ between IgE and other isotypes. Importantly, class switch recombination to IgE can occur in the mucosae, preferentially through the sequential switching from IgG. Therefore, resident effector cells get rapidly sensitized, and free IgE can be found in mucosal secretions. All these aspects explain the involvement of IgE in respiratory diseases. In allergic rhinitis and allergic asthma, the IgE-sensitization to environmental allergens triggers an eosinophilic inflammation of the airway mucosa of atopic patients. In recent years, growing evidence indicates that some non-atopic patients with nasal reactivity to allergens display nasal eosinophilic inflammation, which could be triggered by the local production of allergen-specific IgE. This phenotype has been termed local allergic rhinitis. Mucosal IgE is also implicated in the pathophysiology of chronic rhinosinusitis with nasal polyps, even though the mechanisms for IgE synthesis might differ in this case. The role of IgE as mediator of airway diseases identify this marker as a therapeutic target. Some biologicals antagonize IgE-mediated inflammation of the airway mucosa, but they have not shown a beneficial long-term effect after discontinuation. In contrast, allergen immunotherapy does not only control the symptoms of airway allergy, but it also induces a long-lasting effect after discontinuation, thus modifying the natural course of the disease. [ABSTRACT FROM AUTHOR]

Background Activated T H 2 cells and eosinophils are hallmarks of the allergic inflammation seen in patients with allergic rhinitis (AR). However, which cells activate and attract T cells and eosinophils to the inflammatory lesion has not been determined. Objective We wanted to assess the role of mucosal mononuclear phagocytes, consisting of monocytes, macrophages, and dendritic cells, in the local allergic inflammatory reaction. Methods Patients with AR and nonatopic control subjects were challenged with pollen extract, and nasal symptoms were recorded. Mucosal biopsy specimens obtained at different time points before and after challenge were used for immunostaining in situ and flow cytometric cell sorting. Sorted mononuclear phagocytes were subjected to RNA extraction and gene expression profiling. Results In an in vivo model of AR, we found that CD14 + monocytes were recruited to the nasal mucosa within hours after local allergen challenge, whereas conventional dendritic cells accumulated after several days of continued provocation. Transcriptomic profiling of mucosal mononuclear phagocytes sorted after 1 week of continued allergen challenge showed an activated phenotype at least partially driven by IL-4 signaling, IL-13 signaling, or both. Importantly, gene expression of several T H 2-related chemokines was significantly upregulated by the mononuclear phagocyte population concomitant with an increased recruitment of CD4 + T cells and eosinophils. Conclusion Our findings suggest that the mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells. Rapid recruitment of CD14 + monocytes to the challenged site indicates that these proinflammatory mononuclear phagocytes have a central role in orchestrating local allergic inflammation. [ABSTRACT FROM AUTHOR]