42 research outputs found

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

    Quantifying fracture geometry with X-ray tomography: Technique of Iterative Local Thresholding (TILT) for 3D image segmentation

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    This paper presents a new method—the Technique of Iterative Local Thresholding (TILT)—for processing 3D X-ray computed tomography (xCT) images for visualization and quantification of rock fractures. The TILT method includes the following advancements. First, custom masks are generated by a fracture-dilation procedure, which significantly amplifies the fracture signal on the intensity histogram used for local thresholding. Second, TILT is particularly well suited for fracture characterization in granular rocks because the multi-scale Hessian fracture (MHF) filter has been incorporated to distinguish fractures from pores in the rock matrix. Third, TILT wraps the thresholding and fracture isolation steps in an optimized iterative routine for binary segmentation, minimizing human intervention and enabling automated processing of large 3D datasets. As an illustrative example, we applied TILT to 3D xCT images of reacted and unreacted fractured limestone cores. Other segmentation methods were also applied to provide insights regarding variability in image processing. The results show that TILT significantly enhanced separability of grayscale intensities, outperformed the other methods in automation, and was successful in isolating fractures from the porous rock matrix. Because the other methods are more likely to misclassify fracture edges as void and/or have limited capacity in distinguishing fractures from pores, those methods estimated larger fracture volumes (up to 80 %), surface areas (up to 60 %), and roughness (up to a factor of 2). These differences in fracture geometry would lead to significant disparities in hydraulic permeability predictions, as determined by 2D flow simulations

    Physical conditions and chemical abundances in photoionized nebulae from optical spectra

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    This chapter presents a review on the latest advances in the computation of physical conditions and chemical abundances of elements present in photoionized gas H II regions and planetary nebulae). The arrival of highly sensitive spectrographs attached to large telescopes and the development of more sophisticated and detailed atomic data calculations and ionization correction factors have helped to raise the number of ionic species studied in photoionized nebulae in the last years, as well as to reduce the uncertainties in the computed abundances. Special attention will be given to the detection of very faint lines such as heavy-element recombination lines of C, N and O in H II regions and planetary nebulae, and collisionally excited lines of neutron-capture elements (Z >30) in planetary nebulae.Comment: Book Chapter. 31 pages. 6 Figures. Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

    Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

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    The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

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