Some aspects of presumed filtered density functions formulation in the context of large eddy simulation of turbulent reacting flows

In Large Eddy Simulations (LES) of turbulent flows, spatially-averaged versions of the Navier-Stokes equations are solved on a grid, which is coarse relative to the smallest turbulent length scales. In order to couple the detailed chemistry and the computed flow field in LES of reacting flows, the so-called filtered density function-based approach for subfilter-scale modelling was suggested. This approach was named as the laminar flamelet and allowed to link the complex chemistry to a single variable, i.e. mixture fraction. The mixture fraction is obtained by the solution of corresponding filtered transport equation and subgrid-scale (SGS) variance (the residual field) is usually modelled. The objective of this article is to present in-depth analysis of filtered density functions (FDFs) by analysing experimental data obtained from two-dimensional planar, laser induced fluorescence measurements in isothermal swirling coaxial turbulent jets at a constant Reynolds number of 29000. The FDFs were analysed as a function of flow swirl number, spatial locations in the flow and were linked to the measured subgrid scale variance. In addition, presumed FDFs were also analysed and associated laminar flamelet solution integration errors were evaluated. It was experimentally found that the FDFs can become unimodal when SGS variance reaches a certain value. However, bimodal FDFs were observed in flow regions with high SGS variance. It was demonstrated that bimodality does not automatically result in large errors in resolved variables when top-hat FDF or -FDF formulations are used. It was suggested that possible source of errors in resolved variables could be linked to the SGS variance models rather than to the presumed FDF-based models

Intranasal peptide-induced tolerance and linked suppression: consequences of complement deficiency.

A role for complement, particularly the classical pathway, in the regulation of immune responses is well documented. Deficiencies in C1q or C4 predispose to autoimmunity, while deficiency in C3 affects the suppression of contact sensitization and generation of oral tolerance. Complement components including C3 have been shown to be required for both B-cell and T-cell priming. The mechanisms whereby complement can mediate these diverse regulatory effects are poorly understood. Our previous work, using the mouse minor histocompatibility (HY) model of skin graft rejection, showed that both C1q and C3 were required for the induction of tolerance following intranasal peptide administration. By comparing tolerance induction in wild-type C57BL/6 and C1q-, C3-, C4- and C5-deficient C57BL/6 female mice, we show here that the classical pathway components including C3 are required for tolerance induction, whereas C5 plays no role. C3-deficient mice failed to generate a functional regulatory T (Treg) -dendritic cell (DC) tolerogenic loop required for tolerance induction. This was related to the inability of C3-deficient DC to up-regulate the arginine-consuming enzyme, inducible nitric oxide synthase (Nos-2), in the presence of antigen-specific Treg cells and peptide, leading to reduced Treg cell generation. Our findings demonstrate that the classical pathway and C3 play a critical role in the peptide-mediated induction of tolerance to HY by modulating DC function

Intraoperative Flurbiprofen Treatment Alters Immune Checkpoint Expression in Patients Undergoing Elective Thoracoscopic Resection of Lung Cancer

Objectives: This study aimed to determine the effect of intraoperative administration of flurbiprofen on postoperative levels of programmed death 1 (PD-1) in patients undergoing thoracoscopic surgery. Materials and Methods: In this prospective double-blind trial, patients were randomized to receive intralipid (control group, n = 34, 0.1 mL/kg, i.v.) or flurbiprofen axetil (flurbiprofen group, n = 34, 50 mg, i.v.) before induction of anesthesia. PD-1 levels on T cell subsets, inflammation, and immune markers in peripheral blood were examined before the induction of anesthesia (T-0) and 24 h (T-1), 72 h (T-2), and 1 week (T-3) after surgery. A linear mixed model was used to determine whether the changes from baseline values (T-0) between groups were significantly different. Results: The increases in the percentage of PD-1((+))CD8((+)) T cells observed at T-1 and T-2 in the control group were higher than those in the flurbiprofen group (T-1: 12.91 +/- 1.65 vs. 7.86 +/- 5.71%, p = 0.031; T-2: 11.54 +/- 1.54 vs. 8.75 +/- 1.73%, p = 0.004), whereas no differences were observed in the changes in the percentage of PD-1((+))CD4((+)) T cells at T-1 and T-2 between the groups. Moreover, extensive changes in the percentage of lymphocyte subsets and inflammatory marker concentrations were observed at T-1 and T-2 after surgery and flurbiprofen attenuated most of these changes. Conclusions: Perioperative administration of flurbiprofen attenuated the postoperative increase in PD-1 levels on CD8((+)) T cells up to 72 h after surgery, but not after this duration. The clinical relevance of changes in PD-1 levels to long-term surgical outcome remains unknown

An activity-based integrated land-use transport model for urban spatial distribution simulation

This research develops an activity-based integrated land use/transport interaction model based on the concepts – activities (mainly, households and employment activities), activity location and relocation for Chinese regions. It consists of a residential and employment location sub-model, a transport sub-model and an implicit real estate rent adjustment sub-model. The model is developed to model the urban activity distribution evolution, predict urban spatial development trends and examine various planning decision implications. It spatially distributes household and employment activity change of a study area by zone based on the current activity distribution, land use policies and the accessibilities of the zones. The model is subsequently calibrated to predict the distribution of households and employment activities in Beijing metropolitan area in 2025. Model results show that the resident and employment densities are still high in central Beijing in 2025, and most zones’ resident densities are higher than their employment densities. However, there is also significant population density increase along the 6th ring road, indicating the relocation trend of the residents and businesses to the outskirts. This is consistent with the government objectives to decentralize activities within the central urban area. The paper also suggests that the model should be used mainly in examining the possible differences arising from the adoption of different policies though predicting future of a city distribution proves feasible

Involvement of glomerular renin−angiotensin system (RAS) activation in the development and progression of glomerular injury

Recently, there has been a paradigm shift away from an emphasis on the role of the endocrine (circulating) renin−angiotensin system (RAS) in the regulation of the sodium and extracellular fluid balance, blood pressure, and the pathophysiology of hypertensive organ damage toward a focus on the role of tissue RAS found in many organs, including kidney. A tissue RAS implies that RAS components necessary for the production of angiotensin II (Ang II) reside within the tissue and its production is regulated within the tissue, independent of the circulating RAS. Locally produced Ang II plays a role in many physiological and pathophysiological processes such as hypertension, inflammation, oxidative stress, and tissue fibrosis. Both glomerular and tubular compartments of the kidney have the characteristics of a tissue RAS. The purpose of this article is to review the recent advances in tissue RAS research with a particular focus on the role of the glomerular RAS in the progression of renal disease

Tartrate-resistant acid phosphate as biomarker of bone turnover over the lifespan and different physiologic stages in sheep

Currently, the best resources for assessment of bone tissue using imaging techniques are expensive and available in few medical facilities, thus serum or urinary bone turnover biomarkers could be useful as early indicators of prognosis. However, there is a wide range of variability in bone turnover markers due to several factors, such as different ages and metabolic stages, thus it is important to have as much data published on the subject as possible. The aim of this study was therefore to generate a reference range for alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) and validate the already published data.National Council for Scientific and Technological Development (CNPq - Brazil) PhD scholarship 202248/2015–1.info:eu-repo/semantics/publishedVersio

Why are mineralocorticoid receptor antagonists cardioprotective?

Two clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effect could not be attributed solely to blockade of the renal MR-mediated effects on blood pressure, and it has therefore been proposed that aldosterone, the endogenous MR agonist, also acts extrarenally, in particular in the heart. Indeed, MR are present in cardiac tissue, and possibly aldosterone synthesis occurs in the heart. This review critically addresses the following questions: (1) is aldosterone synthesized at cardiac tissue sites, (2) what agonist stimulates cardiac MR normally, and (3) what effects are mediated by aldosterone/MR in the heart that could explain the beneficial effects of MR blockade in heart failure? Conclusions are that most, if not all, of cardiac aldosterone originates in the circulation (i.e., is of adrenal origin), and that glucocorticoids, in addition to aldosterone, may serve as the endogenous agonist of cardiac MR. MR-mediated effects in the heart include effects on endothelial function, cardiac fibrosis and hypertrophy, oxidative stress, cardiac inotropy, coronary flow, and arrhythmias. Some of these effects occur via or in synergy with angiotensin II, and involve a non-MR-mediated mechanism. This raises the possibility that aldosterone synthase inhibitors might exert beneficial effects on top of MR blockade

In situ Biological Dose Mapping Estimates the Radiation Burden Delivered to ‘Spared’ Tissue between Synchrotron X-Ray Microbeam Radiotherapy Tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to ‘spared’ tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30–40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies