Muscarinic Receptors Mediated Stimulation and Intracellular Signaling Pathways Involved in Human Lung Fibroblast Proliferation

Asthma and chronic obstructive pulmonary disease (COPD) are two diseases characterized by airflow limitation. The most important difference between asthma and COPD is the nature of inflammation, which is primarily eosinophilic and CD-4 driven in asthma, and neutrophilic and CD-8 driven in COPD. In spite of these differences fibrotic alterations are observed in both these diseases. Cholinergic pathway represents key mechanisms in control of airway smooth muscle tone. Anticholinergic bronchodilaters reduce vagal cholinergic tone, the main reversible component in COPD hence constitute an essential element in the therapy of obstructive airways diseases especially in COPD. Furthermore tiotropium bromide (Spiriva®) a long acting muscarinic antagonist was found to delay the decline in airway function in COPD, suggesting that cholinergic mechanisms plays a pivotal role in the structural changes associated with airway remodeling. In studies carried out on human and bovine airway smooth muscle it was seen that muscarinic agonists enhanced the proliferative response to epidermal growth factor and platelet-dervied growth factor respectively. Moreover, tiotropium was found to attenuate the increase in airway smooth muscle mass and myosin expression induced by repeated allergen challenges. Almost every cell type in the airways expresses cholinoreceptor and hence could be a target for acetylcholine released from neuronal or nonneuronal sources. Expression of mRNA encoding different nicotinic receptor subunits and M2 receptors in airway fibroblasts has been described, but a detailed study on expression of muscarinic receptor subtypes in lung and airway fibroblasts is still lacking. The purpose of this study was to determine the expression pattern of the muscarinic receptors in human lung fibroblasts and to investigate whether muscarinic receptors mediate effects on cell proliferation and if so, to elucidate the intracellular signaling pathways entailed. Our studies indicated that human lung fibroblasts indeed express muscarinic receptors with the most dominantly expressed subtype being the M2 receptor, which appears to mediate proliferative stimulus via a Gi/o-Raf-1-MEK-MAPK/ERK pathway, an effect which might contribute to structural changes known to occur in chronic obstructive airway diseases. Prolonged blockade of these receptors may contribute to the long term beneficial effects of anticholinergics, as observed for example, for the long-acting muscarinic antagonist, tiotropium, in COPD

Advances in Perovskite Optoelectronics: Bridging the Gap Between Laboratory and Fabrication

In 2019, hybrid halide perovskites celebrated their 10th anniversary as a "wonder material" for optoelectronic applications. Although the parent perovskite structures were elucidated in the late 19th century, the seminal work by Miyasaka et al. exploiting organic‐inorganic hybrid halide perovskites sensitizers for visible‐light conversion in solar cells marked the revisit of these materials and has proven to be a game‐changer in this field. Extensive investigations were undertaken to develop new materials (all inorganic and organic‐inorganic hybrids, in the form of films or alternate morphologies) and deposition techniques, explore interfaces and in‐depth characterization, while engineering devices and testing methods for optimum results. Within a short time span, the power conversion efficiency (PCE) of single‐junction and tandem perovskite solar cells (PSCs) have exceeded 25% and 29% respectively; thus challenging the dominance of silicon solar cells. Building‐integrated photovoltaics (BIPV) is another hot topic in PSCs, where perovskite solar cells are designed to be semi‐transparent for deployment in residential or office building facades. Along with the success in photovoltaics, halide perovskites have also made their impact in light emission, lasing, imaging, spintronics, memristors, and photocatalysis. However, key challenges still lie ahead, particularly on the commercialization of perovskite devices. Poor material and device stability under operational conditions and the lack of reproducibility and scalability have remained problematic; whereas the search for suitable lead‐free perovskites continues

Homogeneous and heterogeneous catalysts for multicomponent reactions

[EN] Organic synthesis performed through multicomponent reactions is an attractive area of research in organic chemistry. Multicomponent reactions involve more than two starting reagents that couple in an exclusive ordered mode under the same reaction conditions to form a single product which contains the essential parts of the starting materials. Multicomponent reactions are powerful tools in modern drug discovery processes, because they are an important source of molecular diversity, allowing rapid, automated and high throughput generation of organic compounds. This review aims to illustrate progress in a large variety of catalyzed multicomponent reactions performed with acid, base and metal heterogeneous and homogeneous catalysts. Within each type of multicomponent approach, relevant products that can be obtained and their interest for industrial applications are presented.The authors wish to gratefully acknowledge the Generalitat Valenciana for the financial support in the project CONSOLIDER-INGENIO 2010 (CSD2009-00050)Climent Olmedo, MJ.; Corma Canós, A.; Iborra Chornet, S. (2012). Homogeneous and heterogeneous catalysts for multicomponent reactions. RSC Advances. 2(1):16-58. https://doi.org/10.1039/c1ra00807bS16582

Numerical experiments on tides and surges with DUCHESS model

Results of numerical experiments on tides and storm surge in the North Sea, Bay of Bengal and Arabian Sea with the Duchess model are presented. A detailed description of the parametric type of cyclone model developed for Duchess, along with its documentation and source listing is also given in this report. The model simulated reasonably realistic values for tides, but it gave slightly higher values for surges. It needs proper calibration in the case of surge computation.Hydraulic EngineeringCivil Engineering and Geoscience

Diagnostic circulation model for the sensitivity of eddy viscosity coefficients in the western tropical Indian Ocean

195-203The sensitivity of a 18-level diagnostic model of circulation to two different values of horizontal eddy viscosity coefficients has been investigated. Vertical eddy viscosity coefficient has been kept constant in both the experiments. Model driven with January mean wind and thermohaline fields attained steady state within 15 days of model integration. Computed results at 10, 100 and 500 m depth for both the experiments are presented in this paper. Circulation features at 10 m depth in terms of both the magnitude and direction are identical for both the numerical experiments although the horizontal eddy viscosity coefficient was increased two-fold in the second experiment. However, the magnitude of circulation at 100 and 500 m depths was found to decrease marginally in those regions where strong currents were observed. Dynamics of circulation at the above mentioned depths is explained in terms of the forcing parameters and other dynamical. characteristics of the model. It has been found that the surface circulation is mainly controlled by wind field and the subsurface circulation patterns by thermohaline forcing