Cytokine and Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells (ILC2s) in Human Allergic Airway Disease.

The recent discovery of group 2 innate lymphoid cells (ILC2s) has caused a paradigm shift in the understanding of allergic airway disease pathogenesis. Prior to the discovery of ILC2s, Th2 cells were largely thought to be the primary source of type 2 cytokines; however, activated ILC2s have since been shown to contribute significantly, and in some cases, dominantly to type 2 cytokine production. Since the discovery of ILC2s in 2010, many mediators have been shown to regulate their effector functions. Initial studies identified the epithelial derived cytokines IL-25, IL-33, and TSLP as activators of ILC2s, and recent studies have identified many additional cytokine and lipid mediators that are involved in ILC2 regulation. ILC2s and their mediators represent novel therapeutic targets for allergic airway diseases and intensive investigation is underway to better understand ILC2 biology and upstream and downstream pathways that lead to ILC2-driven airway pathology. In this review, we will focus on the cytokine and lipid mediators that regulate ILC2s in human allergic airway disease, as well as highlight newly discovered mediators of mouse ILC2s that may eventually translate to humans

Diagnosis and management of eosinophilic asthma: a US perspective.

Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma

Type 2 Innate Lymphoid Cells in Allergic Disease.

Type II innate lymphoid cells (ILC2) are a novel population of lineage-negative cells that produce high levels of Th2 cytokines IL-5 and IL-13. ILC2 are found in human respiratory and gastrointestinal tissue as well as in skin. Studies from mouse models of asthma and atopic dermatitis suggest a role for ILC2 in promoting allergic inflammation. The epithelial cytokines IL-25, IL-33, and TSLP, as well as the lipid mediator leukotriene D4, have been shown to potently activate ILC2 under specific conditions and supporting the notion that many separate pathways in allergic disease may result in stimulation of ILC2. Ongoing investigations are required to better characterize the relative contribution of ILC2 in allergic inflammation as well as mechanisms by which other cell types including conventional T cells regulate ILC2 survival, proliferation, and cytokine production. Importantly, therapeutic strategies to target ILC2 may reduce allergic inflammation in afflicted individuals. This review summarizes the development, surface marker profile, cytokine production, and upstream regulation of ILC2, and focuses on the role of ILC2 in common allergic diseases

Rigorous Multicomponent Reactive Separations Modelling : Complete Consideration of Reaction-Diffusion Phenomena

This paper gives the first step of the development of a rigorous multicomponent reactive separation model. Such a model is highly essential to further the optimization of acid gases removal plants (CO2 capture, gas treating, etc.) in terms of size and energy consumption, since chemical solvents are conventionally used.Firstly, two main modelling approaches are presented: the equilibrium-based and the rate-based approaches. Secondly, an extended rate-based model with rigorous modelling methodology for diffusion-reaction phenomena is proposed. The film theory and the generalized Maxwell-Stefan equations are used in order to characterize multicomponent interactions. The complete chain of chemical reactions is taken into account. The reactions can be kinetically controlled or at chemical equilibrium, and they are considered for both liquid film and liquid bulk. Thirdly, the method of numerical resolution is described. Coupling the generalized Maxwell-Stefan equations with chemical equilibrium equations leads to a highly non-linear Differential-Algebraic Equations system known as DAE index 3. The set of equations is discretized with finite-differences as its integration by Gear method is complex. The resulting algebraic system is resolved by the Newton- Raphson method. Finally, the present model and the associated methods of numerical resolution are validated for the example of esterification of methanol. This archetype non-electrolytic system permits an interesting analysis of reaction impact on mass transfer, especially near the phase interface. The numerical resolution of the model by Newton-Raphson method gives good results in terms of calculation time and convergence. The simulations show that the impact of reactions at chemical equilibrium and that of kinetically controlled reactions with high kinetics on mass transfer is relatively similar. Moreover, the Fick’s law is less adapted for multicomponent mixtures where some abnormalities such as counter-diffusion take place

Imagining Artificial Intelligence Applications with People with Visual Disabilities Using Tactile Ideation

There has been a surge in artificial intelligence (AI) technologies co-opted by or designed for people with visual disabilities. Researchers and engineers have pushed technical boundaries in areas such as computer vision, natural language processing, location inference, and wearable computing. But what do people with visual disabilities imagine as their own technological future? To explore this question, we developed and carried out tactile ideation workshops with participants in the UK and India. Our participants generated a large and diverse set of ideas, most focusing on ways to meet needs related to social interaction. In some cases, this was a matter of recognizing people. In other cases, they wanted to be able to participate in social situations without foregrounding their disability. It was striking that this finding was consistent across UK and India despite substantial cultural and infrastructural differences. In this paper, we describe a new technique for working with people with visual disabilities to imagine new technologies that are tuned to their needs and aspirations. Based on our experience with these workshops, we provide a set of social dimensions to consider in the design of new AI technologies: social participation, social navigation, social maintenance, and social independence. We offer these social dimensions as a starting point to forefront users' social needs and desires as a more deliberate consideration for assistive technology design

Self-Consistent Measurement and State Tomography of an Exchange-Only Spin Qubit

We report initialization, complete electrical control, and single-shot readout of an exchange-only spin qubit. Full control via the exchange interaction is fast, yielding a demonstrated 75 qubit rotations in under 2 ns. Measurement and state tomography are performed using a maximum-likelihood estimator method, allowing decoherence, leakage out of the qubit state space, and measurement fidelity to be quantified. The methods developed here are generally applicable to systems with state leakage, noisy measurements, and non-orthogonal control axes.Comment: contains Supplementary Informatio

Molecular basis for PrimPol recruitment to replication forks by RPA

DNA damage and secondary structures can stall the replication machinery. Cells possess numerous tolerance mechanisms to complete genome duplication in the presence of such impediments. In addition to translesion synthesis (TLS) polymerases, most eukaryotic cells contain a multi-functional replicative enzyme called Primase-Polymerase (PrimPol) that is capable of directly bypassing DNA damage by TLS, as well as repriming replication downstream of impediments. Here, we report that PrimPol is recruited to reprime through its interaction with RPA. Using biophysical and crystallographic approaches, we identify that PrimPol possesses two RPA-binding motifs and ascertained the key residues required for these interactions. We demonstrate that one of these motifs is critical for PrimPolʼs recruitment to stalled replication forks in vivo. In addition, biochemical analysis reveals that RPA serves to stimulate the primase activity of PrimPol. Together, these findings provide significant molecular insights into PrimPolʼs mode of recruitment to stalled forks to facilitate repriming and restart

Munchausen by internet: current research and future directions.

The Internet has revolutionized the health world, enabling self-diagnosis and online support to take place irrespective of time or location. Alongside the positive aspects for an individual's health from making use of the Internet, debate has intensified on how the increasing use of Web technology might have a negative impact on patients, caregivers, and practitioners. One such negative health-related behavior is Munchausen by Internet

University of Missouri- St. Louis Comprehensive School Safety Initiative (UMSL CSSI)

View the website for this project here: https://www.umsl.edu/ccj/research/cssi.htm