A fully quantum mechanical calculation of the diffusivity of hydrogen in iron using the tight binding approximation and path integral theory

We present calculations of free energy barriers and diffusivities as functions of temperature for the diffusion of hydrogen in bcc-Fe. This is a fully quantum mechanical approach since the total energy landscape is computed using a new self consistent, transferable tight binding model for interstitial impurities in magnetic iron. Also the hydrogen nucleus is treated quantum mechanically and we compare here two approaches in the literature both based in the Feynman path integral formulation of statistical mechanics. We find that the quantum transition state theory which admits greater freedom for the proton to explore phase space gives result in better agreement with experiment than the alternative which is based on fixed centroid calculations of the free energy barrier. We also find results in better agreement compared to recent centroid molecular dynamics (CMD) calculations of the diffusivity which employed a classical interatomic potential rather than our quantum mechanical tight binding theory. In particular we find first that quantum effects persist to higher temperatures than previously thought, and conversely that the low temperature diffusivity is smaller than predicted in CMD calculations and larger than predicted by classical transition state theory. This will have impact on future modeling and simulation of hydrogen trapping and diffusion

The influence of hydrogen on plasticity in pure iron-theory and experiment

Tensile stress relaxation is combined with transmission electron microscopy to reveal dramatic changes in dislocation structure and sub structure in pure alpha iron as a result of the effects of dissolved hydrogen. We find that hydrogen charged specimens after plastic deformation display a very characteristic pattern of trailing dipoles and prismatic loops which are absent in uncharged pure metal. We explain these observations by use of a new self consistent kinetic Monte Carlo model, which in fact was initially used to predict the now observed microstructure. The results of this combined theory and experimental study is to shed light on the fundamental mechanism of hydrogen enhanced localised plasticity

Mucosa-associated invariant T cells link intestinal immunity with antibacterial immune defects in alcoholic liver disease

Background/aims: Intestinal permeability with systemic distribution of bacterial products are central in the immunopathogenesis of alcoholic liver disease (ALD), yet links with intestinal immunity remain elusive. Mucosa-associated invariant T cells (MAIT) are found in liver, blood and intestinal mucosa and are a key component of antibacterial host defences. Their role in ALD is unknown. Methods/design: We analysed frequency, phenotype, transcriptional regulation and function of blood MAIT cells in severe alcoholic hepatitis (SAH), alcohol-related cirrhosis (ARC) and healthy controls (HC). We also examined direct impact of ethanol, bacterial products from faecal extracts and antigenic hyperstimulation on MAIT cell functionality. Presence of MAIT cells in colon and liver was assessed by quantitative PCR and immunohistochemistry/gene expression respectively. Results: In ARC and SAH, blood MAIT cells were dramatically depleted, hyperactivated and displayed defective antibacterial cytokine/cytotoxic responses. These correlated with suppression of lineage-specific transcription factors and hyperexpression of homing receptors in the liver with intrahepatic preservation of MAIT cells in ALD. These alterations were stronger in SAH, where surrogate markers of bacterial infection and microbial translocation were higher than ARC. Ethanol exposure in vitro, in vivo alcohol withdrawal and treatment with Escherichia coli had no effect on MAIT cell frequencies, whereas exposure to faecal bacteria/antigens induced functional impairments comparable with blood MAIT cells from ALD and significant MAIT cell depletion, which was not observed in other T cell compartments. Conclusions: In ALD, the antibacterial potency of MAIT cells is compromised as a consequence of contact with microbial products and microbiota, suggesting that the ‘leaky’ gut observed in ALD drives MAIT cell dysfunction and susceptibility to infection in these patients

Peg-interferon lambda treatment induces robust innate and adaptive immunity in chronic hepatitis B patients

IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks. In a subgroup of patients, the addition of peg-IFNλ provoked high serum levels of antiviral cytokine IL-18. We also observed the enhancement of natural killer cell polyfunctionality and the recovery of a pan-genotypic HBV-specific CD4+ T cells producing IFN-γ with maintenance of HBV-specific CD8+ T cell antiviral and cytotoxic activities. It was only in these patients that we observed strong virological control with reductions in both viral replication and HBV antigen levels. Here, we show for the first time that in vivo peg-IFNλ displays significant immunostimulatory properties with improvements in the main effectors mediating anti-HBV immunity. Interestingly, the maintenance in HBV-specific CD8+ T cells in the presence of peg-IFNλ is in contrast to previous studies showing that peg-IFNa treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment

Influence of hydrogen core force shielding on dislocation junctions in iron

The influence of hydrogen on dislocation junctions was analysed by incorporating a hydrogen dependent core force into nodal based discrete dislocation dynamics. Hydrogen reduces the core energy of dislocations, which reduces the magnitude of the dislocation core force. We refer to this as hydrogen core force shielding, as it is analogous to hydrogen elastic shielding but occurs at much lower hydrogen concentrations. The dislocation core energy change due to hydrogen was calibrated at the atomic scale accounting for the nonlinear inter-atomic interactions at the dislocation core, giving the model a sound physical basis. Hydrogen was found to strengthen binary junctions and promote the nucleation of dislocations from triple junctions. Simulations of microcantilever bend tests with hydrogen core force shielding showed an increase in the junction density and subsequent hardening. These simulations were performed at a small hydrogen concentration realistic for bcc iron