Adding zinc (II) cations and formate anions improves the thermal phase stability of α-FAPbI3 materials, and the spin-coated thin films of such doped FAPbI3 (produced using MACl) show an increased ...emission lifetime of up to 3.7 μs on quartz (for FA0.8MA0.2PbI3). This work investigates the effects of zinc and formate on the phase stability and time-resolved photoluminescence of FAPbI3 perovskites for solar cell applications. Perovskite samples with varying concentrations of zinc and formate were made by incorporating different amounts of zinc formate and zinc iodide and were characterized with XRD. Doping levels of 1.7% Zn(II) and 1.0% formate (relative to Pb) seem optimal. The thermal phase stability of the doped perovskite powders (FAPbI3) and thin films (FA0.8MA0.2PbI3) was assessed. XRD of the thin films after 6 months shows only the alpha-phase. The time-resolved photoluminescence spectroscopy of the doped spin-coated perovskite samples (FA0.8MA0.2PbI3 produced using MACl) is reported. The results show that synergy between an anionic and a cationic dopant can take place, making the perovskite thermally more phase-stable (not converting to the yellow delta-phase) with a longer charge carrier lifetime. In order to produce good thin films by spin coating, the use of MACl was essential.
The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be ...better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are mainly known as a combination drug to attenuate side-effects of chemotherapies. However, endogenous extra-adrenal GC have been shown to substantially regulate local immune responses within various tissues, including the lung. In this study we investigated whether primary lung tumors have maintained the capacity to synthesize GC and may thereby regulate anti-tumor immune responses. We show that several non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) cell lines express key steroidogenic enzymes and synthesize bioactive GC under steady state conditions. We also show that tumor-derived GC can inhibit splenic T cell activation, thus demonstrating their immunoregulatory potential. Moreover, steroidogenic enzymes were detected by quantitative RT-PCR and immunohistochemistry in tissue sections of different human lung tumors, further strengthening the idea that human lung carcinomas regulate their microenvironment by releasing immunoregulatory GC, which potentially contributes to immune evasion and treatment resistance.
The anti-inflammatory role of extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers is of increasing interest with regard to the search for alternatives to synthetic corticosteroids in ...the therapy of inflammatory disorders. Despite being very effective in many situations the use of synthetic corticosteroids is often controversial, as exemplified in the treatment of influenza patients and only recently in the current COVID-19 pandemic. Exploring the regulatory capacity of locally produced GCs in balancing immune responses in barrier tissues and in pathogenic disorders that lead to symptoms in multiple organs, could provide new perspectives for drug development. Intestine, skin and lung represent the first contact zones between potentially harmful pathogens or substances and the body, and are therefore important sites of immunoregulatory mechanisms. Here, we review the role of locally produced GCs in the regulation of type 2 immune responses, like asthma, atopic dermatitis and ulcerative colitis, as well as type 1 and type 3 infectious, inflammatory and autoimmune diseases, like influenza infection, psoriasis and Crohn's disease. In particular, we focus on the role of locally produced GCs in the interorgan communication, referred to as gut-skin axis, gut-lung axis or lung-skin axis, all of which are interconnected in the pathogenic crosstalk atopic march.
The Large Eddy Simulation/System Identification (LES/SI) approach allows to deduce a flame transfer function (FTF) from LES of turbulent reacting flow: Time series of fluctuations of reference ...velocity and global heat release rate resulting from broad-band excitation of a simulated turbulent flame are post-processed via SI techniques to derive a low order model of the flame dynamics, from which the FTF is readily deduced. The current work investigates an extension of the established LES/SI approach: In addition to estimation of the FTF, a low order model for the combustion noise source is deduced from the same time series data. By incorporating such a noise model into a linear thermoacoustic model, it is possible to predict the overall level as well as the spectral distribution of sound pressure in confined combustion systems that do not exhibit self-excited thermoacoustic instability. A variety of model structures for estimation of a noise model are tested in the present study. The suitability and quality of these model structures are compared against each other, their sensitivity regarding certain time series properties is studied. The influence of time series length, signal-to-noise ratio as well as acoustic reflection coefficient of the boundary conditions on the identification are examined. It is shown that the Box-Jenkins model structure is superior to simpler approaches for the simultaneous identification of models that describe the FTF as well as the combustion noise source. Subsequent to the question of the most adequate model structure, the choice of optimal model order is addressed, as in particular the optimal parametrization of the noise model is not obvious. Akaike's Information Criterion and a model residual analysis are applied to draw qualitative and quantitative conclusions on the most suitable model order. All investigations are based on a surrogate data model, which allows a Monte Carlo study across a large parameter space with modest computationally effort. The conducted study constitutes a solid basis for the application of advanced SI techniques to actual LES data.
Background
Extra-adrenal glucocorticoid (GC) synthesis at epithelial barriers, such as skin and intestine, has been shown to be important in the local regulation of inflammation. However, the role of ...local GC synthesis in the lung is less well studied. Based on previous studies and the uncontentious efficacy of corticosteroid therapy in asthma patients, we here investigated the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1/
Hsd11b1
)-dependent local GC reactivation in the regulation of allergic airway inflammation.
Methods
Airway inflammation in Hsd11b1-deficient and C57BL/6 wild type mice was analyzed after injection of lipopolysaccharide (LPS) and anti-CD3 antibody, and in acute and chronic models of airway hypersensitivity induced by house dust mite (HDM) extract. The role of 11β-HSD1 in normal and inflammatory conditions was assessed by high dimensional flow cytometry, histological staining, RT-qPCR analysis,
ex vivo
tissue cultures, GC-bioassays and protein detection by ELISA and immunoblotting.
Results
Here we show that lung tissue from Hsd11b1-deficient mice synthesized significantly less GC
ex vivo
compared with wild type animals in response to immune cell stimulation. We further observed a drastically aggravated phenotype in Hsd11b1-deficient mice treated with HDM extract compared to wild type animals. Besides eosinophilic infiltration, Hsd11b1-deficient mice exhibited aggravated neutrophilic infiltration caused by a strong Th17-type immune response.
Conclusion
We propose an important role of 11β-HSD1 and local GC in regulating Th17-type rather than Th2-type immune responses in HDM-induced airway hypersensitivity in mice by potentially controlling Toll-like receptor 4 (TLR4) signaling and cytokine/chemokine secretion by airway epithelial cells.
Large-Eddy Simulation (LES) is combined with advanced System Identification (SI) to simultaneously infer models for the source of combustion noise and the dynamic response to velocity fluctuations of ...a turbulent premixed flame. A Box-Jenkins model structure allows SI of both the noise source and the flame dynamics from time series data generated with single LES. The models that result from this ‘black-box’ SI approach are purely data-driven and do not rely on estimates of characteristic flow or flame parameters, such as turbulence intensity or flame length. In confined combustion systems the spectral distribution of combustion noise is strongly modulated by the cavity acoustics and the flame dynamics. By incorporating the identified models into a network model for the combustor acoustics, a linear Reduced Order Model (ROM) is built to predict the spectral distribution of sound pressure within the combustor for two different outlet reflection conditions. The identified flame transfer function as well as the ROM-based predictions of the pressure spectra in the combustor are compared with satisfactory qualitative and quantitative agreement against measurements. An interpretation of the pressure spectra based on eigenmode analysis elucidates the interplay between combustion noise generation, flame dynamics and cavity resonances.
Control of tumour development and growth by the immune system critically defines patient fate and survival. What regulates the escape of colorectal tumours from destruction by the immune system ...remains currently unclear. Here, we investigated the role of intestinal synthesis of glucocorticoids in the tumour development during an inflammation‐induced mouse model of colorectal cancer. We demonstrate that the local synthesis of immunoregulatory glucocorticoids has dual roles in the regulation of intestinal inflammation and tumour development. In the inflammation phase, LRH‐1/Nr5A2‐regulated and Cyp11b1‐mediated intestinal glucocorticoid synthesis prevents tumour development and growth. In established tumours, however, tumour‐autonomous Cyp11b1‐mediated glucocorticoid synthesis suppresses anti‐tumour immune responses and promotes immune escape. Transplantation of glucocorticoid synthesis‐proficient colorectal tumour organoids into immunocompetent recipient mice resulted in rapid tumour growth, whereas transplantation of Cyp11b1‐deleted and glucocorticoid synthesis‐deficient tumour organoids was characterized by reduced tumour growth and increased immune cell infiltration. In human colorectal tumours, high expression of steroidogenic enzymes correlated with the expression of other immune checkpoints and suppressive cytokines, and negatively correlated with overall patients' survival. Thus, LRH‐1‐regulated tumour‐specific glucocorticoid synthesis contributes to tumour immune escape and represents a novel potential therapeutic target.
Extra‐adrenal glucocorticoid synthesis in the intestinal epithelium controls intestinal homeostasis, inflammation and colitis‐associated tumour development in a Liver Receptor Homolog‐1 (LRH‐1/NR5A2)‐regulated manner. LRH‐1 drives proliferation and tumour‐autonomous glucocorticoid synthesis, which suppresses anti‐tumour immune responses and promotes immune escape.
Glucocorticoids (GC), synthesized by the 11β-hydroxylase (Cyp11b1), control excessive inflammation through immunosuppressive actions. The skin was proposed to regulate homeostasis by autonomous GC ...production in keratinocytes. However, their immunosuppressive capacity and clinical relevance remain unexplored. Here, we demonstrate the potential of skin-derived GC and their role in the regulation of physiological and prevalent inflammatory skin conditions. In line with 11β-hydroxylase deficiency in human inflammatory skin disorders, genetic in vivo
ablation and long-term GC deficiency in keratinocytes primed the murine skin immune system resulting in spontaneous skin inflammation. Deficient skin GC in experimental models for inflammatory skin disorders led to exacerbated contact hypersensitivity and psoriasiform skin inflammation accompanied by decreased regulatory T cells and the involvement of unconventional T cells. Our findings provide insights on how skin homeostasis and pathology are critically regulated by keratinocyte-derived GC, emphasizing the immunoregulatory potential of endogenous GC in the regulation of epithelial immune microenvironment.
PDF
