Adipose tissue: a neglected organ in the response to severe trauma?

Despite the manifold recent efforts to improve patient outcomes, trauma still is a clinical and socioeconomical issue of major relevance especially in younger people. The systemic immune reaction after severe injury is characterized by a strong pro- and anti-inflammatory response. Besides its functions as energy storage depot and organ-protective cushion, adipose tissue regulates vital processes via its secretion products. However, there is little awareness of the important role of adipose tissue in regulating the posttraumatic inflammatory response. In this review, we delineate the local and systemic role of adipose tissue in trauma and outline different aspects of adipose tissue as an immunologically active modifier of inflammation and as an immune target of injured remote organs after severe trauma

Effects of anesthesia with sevoflurane on outcome parameters in murine experimental studies

Purpose Multiple murine studies modelling the immuno-pathophysiological consequences of trauma, shock, burn or sepsis were performed during the last decades. Almost every animal model requires anesthesia for practical and ethical reasons. Furthermore, often, corresponding control groups involve untreated animals without or with a limited exposure to anesthetics. However, the influences of anesthetic drugs on immuno-pathophysiological reactions remain insufficiently investigated. Therefore, we aimed to closer characterize the anesthetic impact exemplified by sevoflurane on the organ performance in mice and thereby investigate the influence of anesthesia itself on major outcome parameters in animal studies. Methods C57/BL6 mice were subjected either to 270 min of sevoflurane narcosis or directly euthanized. Plasma, BAL-fluids, lungs, kidneys, liver and intestine were collected and examined for immunological, functional and morphological changes. Results Systemic levels of the cytokine keratinocyte chemoattractant (KC) were raised in the narcosis group, while concentrations of high mobility group box protein 1 (HMGB-1) as a major inflammatory marker were reduced. In the lungs, levels of HMGB-1 and interleukin 6 (IL-6) were reduced. In contrast, systemic concentrations of intestinal fatty acid binding-protein (i-FABP) as an intestinal damage marker were elevated. Furthermore, liver-type fatty acid binding-protein (L-FABP) levels were lower in the narcosis animals, and inflammatory markers were reduced in liver tissues. Anesthesia also ameliorated the inflammatory reaction in renal tissues, while plasma levels of urea and creatinine were elevated, reflecting either dehydration and/or impaired renal function. Conclusion As anesthesia with sevoflurane exhibited distinct effects in different organs, it is difficult to predict its specific impact on targets of interest in in vivo studies. Therefore, further studies are required to clarify the effects of different anesthetic drugs. Overall, the inclusion of a control group subjected to the same anesthesia protocol as the experimental groups of interest seems helpful to precisely define the inherent impact of the anesthetic when investigating immuno-pathophysiologic conditions in vivo

Treg-Therapy Allows Mixed Chimerism and Transplantation Tolerance Without Cytoreductive Conditioning

Establishment of mixed chimerism through transplantation of allogeneic donor bone marrow (BM) into sufficiently conditioned recipients is an effective experimental approach for the induction of transplantation tolerance. Clinical translation, however, is impeded by the lack of feasible protocols devoid of cytoreductive conditioning (i.e. irradiation and cytotoxic drugs/mAbs). The therapeutic application of regulatory T cells (Tregs) prolongs allograft survival in experimental models, but appears insufficient to induce robust tolerance on its own. We thus investigated whether mixed chimerism and tolerance could be realized without the need for cytoreductive treatment by combining Treg therapy with BM transplantation (BMT). Polyclonal recipient Tregs were cotransplanted with a moderate dose of fully mismatched allogeneic donor BM into recipients conditioned solely with short-course costimulation blockade and rapamycin. This combination treatment led to long-term multilineage chimerism and donor-specific skin graft tolerance. Chimeras also developed humoral and in vitro tolerance. Both deletional and nondeletional mechanisms contributed to maintenance of tolerance. All tested populations of polyclonal Tregs (FoxP3-transduced Tregs, natural Tregs and TGF-β induced Tregs) were effective in this setting. Thus, Treg therapy achieves mixed chimerism and tolerance without cytoreductive recipient treatment, thereby eliminating a major toxic element impeding clinical translation of this approach

How does the rotational direction of an upwind turbine affect its downwind neighbour?

Wind-turbine blades rotate in clockwise direction looking downstream on the rotor. During daytime conditions of the atmospheric boundary layer, the rotational direction has no influence on the turbine wakes. In stably stratified conditions occurring during night, the atmospheric inflow is often characterized by a veering inflow describing a clockwise wind direction change with height in the Northern Hemisphere. A changing wind direction with height interacting with the rotor impacts its wake characteristics (wake elongation, width and deflection). We investigate the impact on the turbine performance (streamwise velocity for power, turbulence kinetic energy for loading) of a downwind turbine considering the four possible combinations of rotational directions of two 5 MW NREL rotors by means of large-eddy simulations. A counterclockwise rotating upwind turbine results in a 4.1% increase of the rotor averaged inflow velocity at the downwind rotor in comparison to a common clockwise rotating upwind turbine rotor. In case of two counterclockwise rotating rotors, the increase is 4.5%. This increase in streamwise velocity is accompanied by a 3.7% increase in rotor averaged turbulence kinetic energy. The performance difference of the downwind rotor (+4.8% increase of cumulative power of both wind turbines, if the upwind rotor rotates counterclockwise) results from the rotational direction dependent amplification or weakening of the spanwise and the vertical wind components, which is the result of the superposition of veering inflow and upwind rotor rotation

The High Affinity IgE Receptor FcεRI Is Expressed by Human Intestinal Epithelial Cells

IgE antibodies play a paramount role in the pathogenesis of various intestinal disorders. To gain insights in IgE-mediated pathophysiology of the gut, we investigated the expression of the high affinity IgE receptor Fc epsilonRI in human intestinal epithelium.Fc epsilonRI alpha-chain, as detected by immunohistochemistry, was positive in epithelial cells for eight of eleven (8/11) specimens from colon cancer patients and 5/11 patients with inflammation of the enteric mucosa. The Fc epsilonRIalpha positive epithelial cells co-expressed Fc epsilonRIgamma, whereas with one exception, none of the samples was positive for the beta-chain in the epithelial layer. The functionality of Fc epsilonRI was confirmed in situ by human IgE binding. In experiments with human intestinal tumor cell lines, subconfluent Caco-2/TC7 and HCT-8 cells were found to express the alpha- and gamma-chains of Fc epsilonRI and to bind IgE, whereas confluent cells were negative for gamma-chains.Our data provide the first evidence that the components of a functional Fc epsilonRI are in vitro expressed by the human intestinal epithelial cells depending on differentiation and, more importantly, in situ in epithelia of patients with colon cancer or gastrointestinal inflammations. Thus, a contribution of Fc epsilonRI either to immunosurveillance or pathophysiology of the intestinal epithelium is suggested

Evaluation of turbulence characteristics in WRF simulations at WiValdi wind park

In this work we evaluate WRF-LES simulations at the WiValdi wind park at Krummendeich, North Germany. To accurately resolve fine-scale turbulence, we employ a high-resolution nested innermost grid with 5 m horizontal grid spacing. The main aim is to accurately reproduce realistic turbulent characteristics observed in neutral and stable atmospheric boundary layers. The so-called cell-perturbation method to accelerate the development of fine-scale three-dimensional turbulence is tested, and results are compared to in-situ observations and to another highly idealized numerical model running in LES mode. While WRF without additional modifications is capable of reproducing the mean wind fields at the WiValdi wind park, it is unable to reproduce the turbulent characteristics observed. With the cell-perturbation method included, results are significantly improved, with turbulent characteristics much closer to observations

Towards LES-RANS/LES coupling for simulation of a wind turbine rotor in a nocturnal atmospheric condition

A segregated approach with either synthetically generated velocity fluctuations or a precursor Large-Eddy Simulation (LES) of the atmospheric boundary layer (ABL) and a subsequent hybrid RANS/LES (HRLS) of the resolved rotor is presented in this paper. At first the approach is validated with synthetically generated velocity fluctuations that resemble neutrally stratified conditions. Subsequently the same turbine is artificially exposed to a stably stratified atmospheric inflow (nocturnal boundary layer) with a comparable mean velocity but different shear and veer characteristics. The HRLS simulations with the neutrally stratified and stably stratified inflow are compared to LESs with an implemented actuator disc (AD) model. The presented work is a first important step towards a digital twin for research wind parks

A stably-stratified atmospheric inflow assimilated to measured mean profiles interacting with a wind park

In this paper, a simulation chain is presented. This method comprises the precursor large-eddy simulation (LES) of a stably-stratified atmospheric boundary layer (ABL), the assimilation of the simulated mean velocities to measured wind profiles, and finally a simulation of the generated turbulent ABL flow passing through two wind turbines in a row. The high-resolved precursor simulation with a horizontal grid spacing of 3 m accounts for the characteristic turbulence of the stably-stratified ABL. Using an assimilation technique, the horizontal velocities are adapted accurately to the measured mean wind profiles for the WiValdi wind farm site at Krummendeich. The wakes of two wind turbines in a row with the assimilated inflow is successfully computed. With the simulation chain presented, it is possible to generate realistic atmospheric inflows for wind-turbine simulations with manageable computational effort