Autophagy in Inflammatory Diseases

Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. During starvation, autophagy exerts a homeostatic function that promotes cell survival by recycling metabolic precursors. Additionally, autophagy can interact with other vital processes such as programmed cell death, inflammation, and adaptive immune mechanisms, and thereby potentially influence disease pathogenesis. Macrophages deficient in autophagic proteins display enhanced caspase-1-dependent proinflammatory cytokine production and the activation of the inflammasome. Autophagy provides a functional role in infectious diseases and sepsis by promoting intracellular bacterial clearance. Mutations in autophagy-related genes, leading to loss of autophagic function, have been implicated in the pathogenesis of Crohn's disease. Furthermore, autophagy-dependent mechanisms have been proposed in the pathogenesis of several pulmonary diseases that involve inflammation, including cystic fibrosis and pulmonary hypertension. Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases associated with inflammation

Emission of gamma rays shifted from resonant absorption by electron-nuclear double transitions in ^{151}Eu^{2+}:CaF_2

We show that the emission of a gamma-ray photon by a nucleus can be influenced by a microwave magnetic field acting on the atomic electrons. We study theoretically these electron-nuclear double transitions (ENDTs) for ^{151}Eu nuclei in a CaF_2 lattice at low temperature, in the presence of a static magnetic field and of a microwave magnetic field. The ENDTs acquire a significant intensity for certain resonance frequencies. The ENDTs are of interest for the identification of the position of the lines in complex M\"{o}ssbauer spectra.Comment: 8 pages; 3 Postscript figures: Fig. 1, Fig. 2(a), Fig. 2(b

Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease

Heme oxygenase (HO), a catabolic enzyme, provides the rate-limiting step in the oxidative breakdown of heme, to generate carbon monoxide (CO), iron, and biliverdin-IXα. Induction of the inducible form, HO-1, in tissues is generally regarded as a protective mechanism. Over the last decade, considerable progress has been made in defining the therapeutic potential of HO-1 in a number of preclinical models of lung tissue injury and disease. Likewise, tissue-protective effects of CO, when applied at low concentration, have been observed in many of these models. Recent studies have expanded this concept to include chemical CO-releasing molecules (CORMs). Collectively, salutary effects of the HO-1/CO system have been demonstrated in lung inflammation/acute lung injury, lung and vascular transplantation, sepsis, and pulmonary hypertension models. The beneficial effects of HO-1/CO are conveyed in part through the inhibition or modulation of inflammatory, apoptotic, and proliferative processes. Recent advances, however, suggest that the regulation of autophagy and the preservation of mitochondrial homeostasis may serve as additional candidate mechanisms. Further preclinical and clinical trials are needed to ascertain the therapeutic potential of HO-1/CO in human clinical disease

Noise-Activated Escape from a Sloshing Potential Well

We treat the noise-activated escape from a one-dimensional potential well of an overdamped particle, to which a periodic force of fixed frequency is applied. We determine the boundary layer behavior, and the physically relevant length scales, near the oscillating well top. We show how stochastic behavior near the well top generalizes the behavior first determined by Kramers, in the case without forcing. Both the case when the forcing dies away in the weak noise limit, and the case when it does not, are examined. We also discuss the relevance of various scaling regimes to recent optical trap experiments.Comment: 9 pages, no figures, REVTeX, expanded versio

I-mode studies at ASDEX Upgrade: L-I and I-H transitions, pedestal and confinement properties

The I-mode is a plasma regime obtained when the usual L-H power threshold is high, e.g. with unfavourable ion B ∇ direction. It is characterised by the development of a temperature pedestal while the density remains roughly as in the L-mode. This leads to a confinement improvement above the L-mode level which can sometimes reach H-mode values. This regime, already obtained in the ASDEX Upgrade tokamak about two decades ago, has been studied again since 2009 taking advantage of the development of new diagnostics and heating possibilities. The I-mode in ASDEX Upgrade has been achieved with different heating methods such as NBI, ECRH and ICRF. The I-mode properties, power threshold, pedestal characteristics and confinement, are independent of the heating method. The power required at the L-I transition exhibits an offset linear density dependence but, in contrast to the L-H threshold, depends weakly on the magnetic field. The L-I transition seems to be mainly determined by the edge pressure gradient and the comparison between ECRH and NBI induced L-I transitions suggests that the ion channel plays a key role. The I-mode often evolves gradually over a few confinement times until the transition to H-mode which offers a very interesting situation to study the transport reduction and its link with the pedestal formation. Exploratory discharges in which n = 2 magnetic perturbations have been applied indicate that these can lead to an increase of the I-mode power threshold by flattening the edge pressure at fixed heating input power: more heating power is necessary to restore the required edge pressure gradient. Finally, the confinement properties of the I-mode are discussed in detail.European Commission (EUROfusion 633053

First analysis of the updated ITPA global H-mode confinement database

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Review Article Autophagy in Inflammatory Diseases

Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. During starvation, autophagy exerts a homeostatic function that promotes cell survival by recycling metabolic precursors. Additionally, autophagy can interact with other vital processes such as programmed cell death, inflammation, and adaptive immune mechanisms, and thereby potentially influence disease pathogenesis. Macrophages deficient in autophagic proteins display enhanced caspase-1-dependent proinflammatory cytokine production and the activation of the inflammasome. Autophagy provides a functional role in infectious diseases and sepsis by promoting intracellular bacterial clearance. Mutations in autophagy-related genes, leading to loss of autophagic function, have been implicated in the pathogenesis of Crohn's disease. Furthermore, autophagy-dependent mechanisms have been proposed in the pathogenesis of several pulmonary diseases that involve inflammation, including cystic fibrosis and pulmonary hypertension. Strategies aimed at modulating autophagy may lead to therapeutic interventions for diseases associated with inflammation