M cells are specialized intestinal epithelial cells that provide the main machinery for sampling luminal microbes for mucosal immune surveillance. M cells are usually found in the epithelium ...overlying organized mucosal lymphoid tissues, but studies have identified multiple distinct lineages of M cells that are produced under different conditions, including intestinal inflammation. Among these lineages there is a common morphology that helps explain the efficiency of M cells in capturing luminal bacteria and viruses; in addition, M cells recruit novel cellular mechanisms to transport the particles across the mucosal barrier into the lamina propria, a process known as transcytosis. These specializations used by M cells point to a novel engineering of cellular machinery to selectively capture and transport microbial particles of interest. Because of the ability of M cells to effectively violate the mucosal barrier, the circumstances of M cell induction have important consequences. Normal immune surveillance insures that transcytosed bacteria are captured by underlying myeloid/dendritic cells; in contrast, inflammation can induce development of new M cells not accompanied by organized lymphoid tissues, resulting in bacterial transcytosis with the potential to amplify inflammatory disease. In this review, we will discuss our own perspectives on the life history of M cells and also raise a few questions regarding unique aspects of their biology among epithelia.
In the research of mining software repositories, we need to label a large amount of data to construct a predictive model. The correctness of the labels will affect the performance of a model ...substantially. However, limited studies have been performed to investigate the impact of mislabeled instances on a predictive model. To bridge the gap, in this article, we perform a case study on the security bug report (SBR) prediction. We found five publicly available datasets for SBR prediction contains many mislabeled instances, which lead to the poor performance of SBR prediction models of recent studies (e.g., the work of Peters et al. and Shu et al. ). Furthermore, it might mislead the research direction of SBR prediction. In this article, we first improve the label correctness of these five datasets by manually analyzing each bug report, and we find 749 SBRs, which are originally mislabeled as Non-SBRs (NSBRs). We then evaluate the impacts of datasets label correctness by comparing the performance of the classification models on both the noisy (i.e., before our correction) and the clean (i.e., after our correction) datasets. The results show that the cleaned datasets result in improvement in the performance of classification models. The performance of the approaches proposed by Peters et al. and Shu et al. on the clean datasets is much better than on the noisy datasets. Furthermore, with the clean datasets, the simple text classification models could significantly outperform the security keywords-matrix-based approaches applied by Peters et al. and Shu et al.
The flow-induced vibrations of a circular cylinder, free to oscillate in the cross-flow direction and subjected to a forced rotation about its axis, are analysed by means of two- and ...three-dimensional numerical simulations. The impact of the symmetry breaking caused by the forced rotation on the vortex-induced vibration (VIV) mechanisms is investigated for a Reynolds number equal to $100$, based on the cylinder diameter and inflow velocity. The cylinder is found to oscillate freely up to a rotation rate (ratio between the cylinder surface and inflow velocities) close to $4$. Under forced rotation, the vibration amplitude exhibits a bell-shaped evolution as a function of the reduced velocity (inverse of the oscillator natural frequency) and reaches $1.9$ diameters, i.e. three times the maximum amplitude in the non-rotating case. The free vibrations of the rotating cylinder occur under a condition of wake–body synchronization similar to the lock-in condition driving non-rotating cylinder VIV. The largest vibration amplitudes are associated with a novel asymmetric wake pattern composed of a triplet of vortices and a single vortex shed per cycle, the ${\rm T} + {\rm S}$ pattern. In the low-frequency vibration regime, the flow exhibits another new topology, the U pattern, characterized by a transverse undulation of the spanwise vorticity layers without vortex detachment; consequently, free oscillations of the rotating cylinder may also develop in the absence of vortex shedding. The symmetry breaking due to the rotation is shown to directly impact the selection of the higher harmonics appearing in the fluid force spectra. The rotation also influences the mechanism of phasing between the force and the structural response.
Microfold (M) cells are epithelial cells present in mucosal tissues and specialized for the capture of luminal microparticles and their delivery to underlying immune cells; thus, they are crucial ...participants in mucosal immune surveillance. Multiple phenotypic subsets of M cells have now been described, all sharing a unique apical morphology that provides clues to their ability to capture microbial particles. The existence of diverse M cell phenotypes, especially inflammation-inducible M cells, provides an intriguing puzzle: some variants may augment luminal surveillance to boost mucosal immunity, while others may promote microbial access to tissues. Here, I consider the unique induction requirements of each M cell subset and functional differences, highlighting the potentially distinct consequences in mucosal immunity.
Multiple M cell phenotypes from multiple epithelial origins are being identified, but they share convergent apical membrane morphology.
Different M cell phenotypes are induced by different conditions, which may indicate functional specialization.
M cells capture viruses and bacteria through multiple mechanisms, including electrostatic interactions due to apical surface characteristics, obviating the need for an array of specific capture receptors.
Diagnosing asthma in children represents an important clinical challenge. There is no single gold-standard test to confirm the diagnosis. Consequently, over- and under-diagnosis of asthma is frequent ...in children.
A task force supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine Population, Intervention, Comparator and Outcome (PICO) questions. The task force conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full-text articles. All task force members approved the final decision for inclusion of research papers. The task force assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
The task force then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The task force formulated recommendations using the GRADE Evidence to Decision framework.
Based on the critical appraisal of the evidence and the Evidence to Decision framework, the task force recommends spirometry, bronchodilator reversibility testing and exhaled nitric oxide fraction as first-line diagnostic tests in children under investigation for asthma. The task force recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future.
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