Cholinergic Regulation of Airway Inflammation and Remodelling

Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD

A Comprehensive Review on Planar Magnetics and the Structures to Reduce the Parasitic Elements and Improve Efficiency

Due to the need for highly efficient and compact power electronic converters to operate at higher frequencies, traditional wire-wound magnetics are not suitable. This paper provides a comprehensive review of planar magnetic technologies, discussing their advantages as well as associated disadvantages. An extensive review of the research literature is presented with the aim of suggesting models for planar magnetics. Several strategies are proposed to overcome the limitations of planar magnetics, including winding conduction loss, leakage inductance, and winding capacitance. The goal of this study is to provide engineers and researchers with a clear roadmap for designing planar magnetic devices

Multi-active bridge based DC-link balancing of three-level NPC inverters

A common topic in multilevel converter research is the question of DC-link capacitor voltage balancing. For the three-level neutral point clamped converter the balancing is difficult due to the nonlinear nature of the DC-link capacitor voltages. Previous papers solved this problem using sophisticated controllers or additional circuitry connected in parallel to the load. Those solutions however restrict the performance of the output voltage since the controller has to provide a trade-off between output voltage performance and DC-link balancing while the load-connected balancing circuit puts limitations on the applied modulation scheme. In this paper, we connect a multi-active bridge circuit to the DC-link of the converter to overcome this problem. The proposed method is independent of the modulation scheme of the neutral point clamped converter and allows to use of all possible switching states to control the output voltage without taking the effect on the DC-link balance into account. The efficiency of the proposed method is verified using experimental results

Variable Switching Point Model Predictive Control for DC-Link Voltage Regulation of Back-to-Back Converters

In this paper, a novel control method for back-toback converters used in grid-to-motor connections is explored. To increase the robustness of low DC-link capacitances, a control method based on variable switching point model predictive control is proposed. While previous model predictive control methods for the back-to-back converter selected a certain switching state to fulfill all control goals, we use the switching time in addition to the switching state in order to minimise deviations from the target voltage. Choosing a variable switching point provides an additional degree of freedom to the control framework and allows the system to cope with the large number of control variables. In this case, the variable switching point is used to minimize the effects of low DC-link capacitances on the system. This can either be achieved by selecting a switching point that yields low DClink capacitor charging or by selecting a switching point that aims to keep the DC-link voltage close to the reference. The proposed method is verified through numerical simulations and hardware-in-the-loop (HIL) experiments and compared to existing approaches. The results show that it is possible to control the DClink using only the switching point of the converter

Spurious transcription causing innate immune responses is prevented by 5-hydroxymethylcytosine

Generation of functional transcripts requires transcriptional initiation at regular start sites, avoiding production of aberrant and potentially hazardous aberrant RNAs. The mechanisms maintaining transcriptional fidelity and the impact of spurious transcripts on cellular physiology and organ function have not been fully elucidated. Here we show that TET3, which successively oxidizes 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and other derivatives, prevents aberrant intragenic entry of RNA polymerase II pSer5 into highly expressed genes of airway smooth muscle cells, assuring faithful transcriptional initiation at canonical start sites. Loss of TET3-dependent 5hmC production in SMCs results in accumulation of spurious transcripts, which stimulate the endosomal nucleic-acid-sensing TLR7/8 signaling pathway, thereby provoking massive inflammation and airway remodeling resembling human bronchial asthma. Furthermore, we found that 5hmC levels are substantially lower in human asthma airways compared with control samples. Suppression of spurious transcription might be important to prevent chronic inflammation in asthma

The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

In healthy circumstances the immune system coordinates tissue repair responses in a tight balance that entails efficient inflammation for removal of potential threats, proper wound closure, and regeneration to regain tissue function. Pathological conditions, continuous exposure to noxious agents, and even ageing can dysregulate immune responses after injury. This dysregulation can lead to a chronic repair mechanism known as fibrosis. Alterations in wound healing can occur in many organs, but our focus lies with the lung as it requires highly regulated immune and repair responses with its continuous exposure to airborne threats. Dysregulated repair responses can lead to pulmonary fibrosis but the exact reason for its development is often not known. Here, we review the diversity of innate immune cells of myeloid origin that are involved in tissue repair and we illustrate how these cell types can contribute to the development of pulmonary fibrosis. Moreover, we briefly discuss the effect of age on innate immune responses and therefore on wound healing and we conclude with the implications of current knowledge on the avenues for future research