M1 and M2 activated macrophages (Mϕs) have different roles in inflammation. Because pathogens may first encounter resting cells, we investigated lipid mediator profiles prior to full activation. Human monocytes were differentiated with granulocyte Mϕ colony‐stimulating factor (GM‐CSF) or Mϕ colony‐stimulating factor (M‐CSF), which are known to prime toward M1 or M2 phenotypes, respectively. Lipid mediators released during resting conditions and produced in response to bacterial stimuli (LPS/N‐formylmethionyl‐leucyl‐phenylalanine or peptidoglycan) were quantified by liquid chromatography‐mass spectrometry. In resting conditions, both Mϕ phenotypes released primarily proresolving lipid mediators (prostaglandin E2 metabolite, lipoxin A4, and 18‐hydroxyeicosapentaenoic acid). A striking shift toward proinflammatory eicosanoids was observed when the same cells were exposed (30 min) to bacterial stimuli: M‐CSF Mϕs produced considerably more 5‐lipoxygenase products, particularly leukotriene C4, potentially linked to M2 functions in asthma. Prostaglandins were formed by both Mϕ types. In the M‐CSF cells, there was also an enhanced release of arachidonic acid and activation of cytosolic phospholipase A2. However, GM‐CSF cells expressed higher levels of 5‐lipoxygenase and 5‐lipoxygenase–activating protein, and in ionophore incubations these cells also produced the highest levels of 5‐hydroxyeicosatetraenoic acid. In summary, GM‐CSF and M‐CSF Mϕs displayed similar proresolving lipid mediator formation in resting conditions but shifted toward different proinflammatory eicosanoids upon bacterial stimuli. This demonstrates that preference for specific eicosanoid pathways is primed by CSFs before full M1/M2 activation.—Lukic, A., Larssen, P., Fauland, A., Samuelsson, B., Wheelock, C.E., Gabrielsson, S., Radmark, O. GM‐CSF– and M‐CSF–primed macrophages present similar resolving but distinct inflammatory lipid mediator signatures. FASEB J. 31, 4370–4381 (2017). www.fasebj.org
Every long bone fracture in orthopedic surgery represents a possible scenario for devel- opment of embolism complication, especially the fat embolism. There is no scientific explanation why fat embolism occurs and what are the hypotheses for development of fat embolism or the proper way of prevention, but just speculations and possible theories in the evolution of the clinical picture of fat embolism syndrome. Throughout this chap- ter, the authors will explain the possible theories of development of fat embolism, risk factors, pathology, and pathophysiology during progress of the clinical picture and signs of the fat embolism syndrome and therapy.
Istraživanje ključnih faktora kvalitete procesa građevinskih projakata u Bosni i Hercegovini te Hrvatskoj, pokazalo je da te faktore ne prihvaćaju jednako investitori, izvođači/podizvođači i voditelji projekta/konzultanti/projektanati. Prva četiri rangirana faktora su: koordinacija među sudionicima, komunikacija; stručnost/ znanje...; planiranje i kontrola, s različitim prioritetom unutar spomenutih sudionika. Istraživanje je nadalje pokazalo kako tijekom različitih faza građevinskog projekta važnost se pojedinih faktora kvalitete razlikuje s obzirom na različita upravljačka gledišta.
Ionizing radiation from natural sources or anthropogenic activity has the potential to cause oxidative stress or genetic damage in living organisms, through the ionization and excitation of molecules and the subsequent production of free radicals and reactive oxygen species (ROS). The present work focuses on radiation-induced biological effects using the zebrafish (Danio rerio) vertebrate model. Changes in developmental traits and gene expression in zebrafish were assessed after continuous external gamma irradiation (0.4, 3.9, 15 and 38 mGy/h) with corresponding controls, starting at 2.5 hours post fertilization (hpf) and lasting through embryogenesis and the early larval stage. The lowest dose rate corresponded to recommended benchmarks at which adverse effects are not expected to occur in aquatic ecosystems (2–10 mGy/day). The survival observed at 96 hours post fertilization (hpf) in the 38 mGy/h group was significantly lower, while other groups showed no significant difference compared to controls. The total hatching was significantly lower from controls in the 15 mGy/h group and a delay in hatching onset in the 0.4 mGy/h group was observed. The deformity frequency was significantly increased by prolonged exposure duration at dose rates ≥ 0.4 mGy/h. Molecular responses analyzed by RNA-seq at gastrulation (5.5 hpf transcriptome) indicate that the radiation induced adverse effects occurred during the earliest stages of development. A dose-response relationship was found in the numbers of differentially regulated genes in exposure groups compared to controls at a total dose as low as 1.62 mGy. Ingenuity Pathway Analysis identified retinoic acid receptor activation, apoptosis, and glutathione mediated detoxification signaling as the most affected pathways in the lower dose rate (0.54 mGy/h), while eif2 and mTOR, i.e., involved in the modulation of angiogenesis, were most affected in higher dose rates (5.4 and 10.9 mGy/h). By comparing gene expression data, myc was found to be the most significant upstream regulator, followed by tp53, TNF, hnf4a, TGFb1 and cebpa, while crabp2b and vegfab were identified as most frequent downstream target genes. These genes are associated with various developmental processes. The present findings show that continuous gamma irradiation (≥ 0.54 mGy/h) during early gastrula causes gene expression changes that are linked to developmental defects in zebrafish embryos.
Penetration of grid connected inverters (GCI) has arisen in power systems due to increasing integration of renewable sources. However, restrictive grid codes require that renewable sources connected to the grid with power electronic systems must be properly connected and appropriate currents must be injected to support stability of the grid under grid faults. Simultaneous injection of symmetrical positive and negative sequence currents is mandatory to support stabilization of grid at the instant of grid faults. Conventional synchronously rotating frame dq current controllers are insufficient under grid faults due to low bandwidth of PI controllers. This paper proposes a new grid current control strategy for grid connected voltage source inverters under unbalanced grid voltage conditions. A proportional current controller with a first order low pass filter disturbance observer (DOb) is proposed which establishes positive sequence power requirements and independently control negative sequence current components under unbalanced voltage conditions. The method does not need any parameter, since it estimates nonlinear terms with low pass filter DOb. Simulations are implemented in Matlab/Simulink platform demonstrating the effectiveness of proposed method.
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