Local Entropy Characterization of Correlated Random Microstructures

A rigorous connection is established between the local porosity entropy introduced by Boger et al. (Physica A 187, 55 (1992)) and the configurational entropy of Andraud et al. (Physica A 207, 208 (1994)). These entropies were introduced as morphological descriptors derived from local volume fluctuations in arbitrary correlated microstructures occuring in porous media, composites or other heterogeneous systems. It is found that the entropy lengths at which the entropies assume an extremum become identical for high enough resolution of the underlying configurations. Several examples of porous and heterogeneous media are given which demonstrate the usefulness and importance of this morphological local entropy concept.Comment: 15 pages. please contact [email protected] and have a look at http://www.ica1.uni-stuttgart.de/ . To appear in Physica

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

Mixed effect model confirms increased risk of image changes with increasing linear energy transfer in proton therapy of gliomas

BACKGROUND AND PURPOSE: Radiation induced image changes (IC) on MRI have been observed after proton therapy for brain tumours. This study aims to create predictive models, with and without taking into account patient variation, based on dose, linear energy transfer (LET) and periventricular zone (PVZ) in a national cohort of patients with glioma treated with pencil beam scanning (PBS).MATERIALS AND METHODS: A cohort of 87 consecutive patients with oligodendroglioma or astrocytoma (WHO grade 2-4) treated with PBS from January 2019 to December 2021 was included. All patients were treated with three to four beams. Monte Carlo calculations of dose and LET were performed for all treatment plans. Lesion weighted as well as mixed effect logistic regression models were developed to predict IC in a voxel.RESULTS: 12 patients (14 %) developed ICs on the follow-up MR-scans. Mixed effect modelling accounting for interpatient variation was justified by the non-negligible inter class correlation coefficient (ICC = 0.33). The two approaches identified similar model features and marginal improvement in model performance was found, when increasing model parameters from two (AUC = 0.92/0.94) to three (AUC = 0.93/0.95) parameters. Univariate analysis showed that patients treated with narrow beam configurations had an increased incidence of IC (p = 0.01).CONCLUSION: 14% of patients developed IC following PT. Lesion-weighted and mixed effect models resulted in similar model performance confirming increased risk of IC with increasing LET. The beam arrangement seems to influence the risk of IC and needs further investigation.</p

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