Simulation of Deformation-induced Martensite Formation and its Influence on the Resonant Behavior in the Very High Cycle Fatigue (VHCF) Regime

AbstractThe exploration of fatigue mechanisms in the VHCF regime is gaining importance since many components have to withstand a very high number of loading cycles due to high frequency or long product life. In this regime, particular attention is paid to the period of fatigue crack initiation and thus the localization of plastic deformation. The resonant behavior of a metastable austenitic stainless steel (AISI304) is studied experimentally in the VHCF regime and shows a distinct transient characteristic. The major contribution of this work is to obtain a physically-based understanding of this characteristic by modeling the underlying microstructural mechanisms and their influence on the resonant behavior. Microscopic examinations indicate that AISI304 undergoes deformation-induced martensite formation starting mostly at intersecting shear bands during fatigue. Therefore, a microstructural shear band model [Hilgendorff et al. (2013)] is extended regarding the mechanism of deformation-induced martensite formation. The model accounts for the microstructural mechanisms occurring in shear bands as documented by experimental results, and nucleation of martensite is assumed to occur at intersecting shear bands following the Olsen-Cohen nucleation model (1972) in combination with the Bogers-Burgers mechanism (1964). The simulation model is numerically solved using the two-dimensional (2-D) boundary element method. By using this method, a 2-D microstructure can be modeled considering grain orientations as well as individual anisotropic elastic properties in each grain. The resonant behavior is characterized by evaluating the force-displacement hysteresis loop. Results show that plastic deformation in shear bands and deformation-induced martensite formation have a major impact on the resonant behavior in the very high cycle fatigue (VHCF) regime

Enhanced biomedical heat-triggered carriers via nanomagnetism tuning in ferrite-based nanoparticles

Biomedical nanomagnetic carriers are getting a higher impact in therapy and diagnosis schemes while their constraints and prerequisites are more and more successfully confronted. Such particles should possess a well-defined size with minimum agglomeration and they should be synthesized in a facile and reproducible high-yield way together with a controllable response to an applied static or dynamic field tailored for the specific application. Here, we attempt to enhance the heating efficiency in magnetic particle hyperthermia treatment through the proper adjustment of the core–shell morphology in ferrite particles, by controlling exchange and dipolar magnetic interactions at the nanoscale. Thus, core–shell nanoparticles with mutual coupling of magnetically hard (CoFe2O4) and soft (MnFe2O4) components are synthesized with facile synthetic controls resulting in uniform size and shell thickness as evidenced by high resolution transmission electron microscopy imaging, excellent crystallinity and size monodispersity. Such a magnetic coupling enables the fine tuning of magnetic anisotropy and magnetic interactions without sparing the good structural, chemical and colloidal stability. Consequently, the magnetic heating efficiency of CoFe2O4 and MnFe2O4 core–shell nanoparticles is distinctively different from that of their counterparts, even though all these nanocrystals were synthesized under similar conditions. For better understanding of the AC magnetic hyperthermia response and its correlation with magnetic-origin features we study the effect of the volume ratio of magnetic hard and soft phases in the bimagnetic core−shell nanocrystals. Eventually, such particles may be considered as novel heating carriers that under further biomedical functionalization may become adaptable multifunctional heat-triggered nanoplatforms

Effect of surfactant for magnetic properties of iron oxide nanoparticles

For different medical applications nanoparticles (NPs) with well-defined magnetic properties have to be used. Coating ligand can change the magnetic moment on the surface of nanostructures and therefore the magnetic behavior of the system. Here we investigated magnetic NPs in a size of 13 nm conjugated with four different kinds of surfactants. The surface anisotropy and the magnetic moment of the system were changed due to the presence of the surfactant on the surface of iron oxide NPs

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

Gas exchange mechanisms in preterm infants on HFOV - a computational approach

High-frequency oscillatory ventilation (HFOV) is a commonly used therapy applied to neonates requiring ventilatory support during their first weeks of life. Despite its wide application, the underlying gas exchange mechanisms promoting the success of HVOF in neonatal care are not fully understood until today. In this work, a highly resolved computational lung model, derived from Magnetic Resonance Imaging (MRI) and Infant Lung Function Testing (ILFT), is used to reveal the reason for highly efficient gas exchange during HFOV, in the preterm infant. In total we detected six mechanisms that facilitate gas exchange during HFOV: (i) turbulent vortices in large airways;(ii) asymmetric in-and expiratory flow profiles;(iii) radial mixing in main bronchi;(iv) laminar flow in higher generations of the respiratory tract;(v) pendelluft;(vi) direct ventilation of central alveoli. The illustration of six specific gas transport phenomena during HFOV in preterm infants advances general knowledge on protective ventilation in neonatal care and can support decisions on various modes of ventilatory therapy at high frequencies

C/EBPβ-Thr217 Phosphorylation Signaling Contributes to the Development of Lung Injury and Fibrosis in Mice

mice are refractory to Bleomycin-induced lung fibrosis the molecular mechanisms remain unknown. Here we show that blocking the ribosomal S-6 kinase (RSK) phosphorylation of the CCAAT/Enhancer Binding Protein (C/EBP)-β on Thr217 (a RSK phosphoacceptor) with either a single point mutation (Ala217), dominant negative transgene or a blocking peptide containing the mutated phosphoacceptor ameliorates the progression of lung injury and fibrosis induced by Bleomycin in mice. mice with a cell permeant, C/EBPβ peptide that inhibits phosphorylation of C/EBPβ on Thr217 (40 µg instilled intracheally on day-2 and day-6 after the single Bleomycin dose) also blocked the progression of lung injury and fibrosis induced by Bleomycin. Phosphorylation of human C/EBPβ on Thr266 (human homologue phosphoacceptor) was induced in collagen-activated human lung fibroblasts in culture as well as in activated lung fibroblasts in situ in lungs of patients with severe lung fibrosis but not in control lungs, suggesting that this signaling pathway may be also relevant in human lung injury and fibrosis.These data suggest that the RSK-C/EBPβ phosphorylation pathway may contribute to the development of lung injury and fibrosis

a transparent plastic varnish with nanoparticulate magnetic additives

For the purpose of preparing TCCs (= transparent and electrical conducting coatings), metallic and ferromagnetic nano-additives were dispersed into a transparent varnish and the obtained dispersions were coated on transparent plastic substrates. During hardening of the dispersion the magnetic nano- additives were aligned by a magnetic field. The resulting coatings have electrical pathways along lines of nano-additive chains and are highly transparent in the areas between the lines. Therefore, the electrical conductivity is anisotropic, and it depends on the alignment of the nano- additives (i.e. on the distance between the nano-additives within the chains and the length of the lines) as well as on the thickness of an oxide and/or solvent shell around the nano-additives. The transparency depends also on the alignment and here especially on the thickness and the distance between the formed lines. The quality of the alignment in turn, depends on the magnetic properties and on the size of the particles. We used commercial plastic varnishes, which form electrically isolating (≥ 10− 12 S/m) and transparent (about 90% transparency) coatings, and the following magnetic additives: Co-, Fe-, CoPt3, CoPt3@Au- and Fe@Au-nanoparticles as well as CoNi-nanowires. Coatings with Fe@Au-nanoparticles show the best results in terms of the electrical conductivity (10− 5 S/m–10− 6 S/m) at transparencies above 70%. Furthermore, in addition to the magnetic nano-additives, transparent additives (Al2O3-particles) and non-magnetic, but better conducting additives (carbon- nanotubes) were added to the varnish to increase the transparency and the electrical conductivity, respectively

Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation

Background: Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. Results: We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture. Conclusions: Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum

Innate Immune Deficiency of Extremely Premature Neonates Can Be Reversed by Interferon-γ

Background: Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants. Methodology/Principal Findings: We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Grampositive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-c. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-c. Conclusion/Significance: Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressivel