A novel technique for selective NF-kappa B inhibition in Kupffer cells: contrary effects in fulminant hepatitis and ischaemia-reperfusion.

Background and aims: The transcription factor nuclear factor kappa B (NF-kB) has risen as a promising target for anti-inflammatory therapeutics. In the liver, however, NFkB inhibition mediates both damaging and protective effects. The outcome is deemed to depend on the liver cell type addressed. Recent gene knock-out studies focused on the role of NF-kB in hepatocytes, whereas the role of NF-kB in Kupffer cells has not yet been investigated in vivo. Here we present a novel approach, which may be suitable for clinical application, to selectively target NF-kB in Kupffer cells and analyse the effects in experimental models of liver injury. Methods: NF-kB inhibiting decoy oligodeoxynucleotides were loaded upon gelatin nanoparticles (D-NPs) and their in vivo distribution was determined by confocal microscopy. Liver damage, NF-kB activity, cytokine levels and apoptotic protein expression were evaluated after lipopolysaccharide (LPS), D-galactosamine (GalN)/LPS, or concanavalin A (ConA) challenge and partial warm ischaemia and subsequent reperfusion, respectively. Results: D-NPs were selectively taken up by Kupffer cells and inhibited NF-kB activation. Inhibition of NF-kB in Kupffer cells improved survival and reduced liver injury after GalN/LPS as well as after ConA challenge. While anti-apoptotic protein expression in liver tissue was not reduced, pro-apoptotic players such as cJun N-terminal kinase (JNK) were inhibited. In contrast, selective inhibition of NF-kB augmented reperfusion injury. Conclusions: NF-kB inhibiting decoy oligodeoxynucleotide- loaded gelatin nanoparticles is a novel tool to selectively inhibit NF-kB activation in Kupffer cells in vivo. Thus, liver injury can be reduced in experimental fulminant hepatitis, but increased at ischaemia–reperfusion

Cost-Efficient Storage of Cryogens

NASA's cryogenic infrastructure that supports launch vehicle operations and propulsion testing is reaching an age where major refurbishment will soon be required. Key elements of this infrastructure are the large double-walled cryogenic storage tanks used for both space vehicle launch operations and rocket propulsion testing at the various NASA field centers. Perlite powder has historically been the insulation material of choice for these large storage tank applications. New bulk-fill insulation materials, including glass bubbles and aerogel beads, have been shown to provide improved thermal and mechanical performance. A research testing program was conducted to investigate the thermal performance benefits as well as to identify operational considerations and associated risks associated with the application of these new materials in large cryogenic storage tanks. The program was divided into three main areas: material testing (thermal conductivity and physical characterization), tank demonstration testing (liquid nitrogen and liquid hydrogen), and system studies (thermal modeling, economic analysis, and insulation changeout). The results of this research work show that more energy-efficient insulation solutions are possible for large-scale cryogenic storage tanks worldwide and summarize the operational requirements that should be considered for these applications

A critical perspective on second-order empathy in understanding psychopathology: phenomenology and ethics

The centenary of Karl Jaspers’ General Psychopathology was recognised in 2013 with the publication of a volume of essays dedicated to his work (edited by Stanghellini and Fuchs). Leading phenomenological-psychopathologists and philosophers of psychiatry examined Jaspers notion of empathic understanding and his declaration that certain schizophrenic phenomena are ‘un-understandable’. The consensus reached by the authors was that Jaspers operated with a narrow conception of phenomenology and empathy and that schizophrenic phenomena can be understood through what they variously called second-order and radical empathy. This article offers a critical examination of the second-order empathic stance along phenomenological and ethical lines. It asks: (1) Is second-order empathy (phenomenologically) possible? (2) Is the second-order empathic stance an ethically acceptable attitude towards persons diagnosed with schizophrenia? I argue that second-order empathy is an incoherent method that cannot be realised. Further, the attitude promoted by this method is ethically problematic insofar as the emphasis placed on radical otherness disinvests persons diagnosed with schizophrenia from a fair chance to participate in the public construction of their identity and, hence, to redress traditional symbolic injustices

Bodily feeling in depersonalisation: a phenomenological account

publication-status: Publishedtypes: ArticlePre-print - please cite published version at Sage web site: http://emr.sagepub.com/content/4/2/145.full.pdf+htmlThis paper addresses the phenomenology of bodily feeling in depersonalisation disorder. We argue that not all bodily feelings are intentional states that have the body or part of it as their object. We distinguish three broad categories of bodily feeling: noematic feeling, noetic feeling and existential feeling. Then we show how an appreciation of the differences between them can contribute to an understanding of the depersonalisation experience.ER

Interannual snow accumulation variability on glaciers derived from repeat, spatially extensive ground-penetrating radar surveys

There is significant uncertainty regarding the spatiotemporal distribution of seasonal snow on glaciers, despite being a fundamental component of glacier mass balance. To address this knowledge gap, we collected repeat, spatially extensive high-frequency ground-penetrating radar (GPR) observations on two glaciers in Alaska during the spring of 5 consecutive years. GPR measurements showed steep snow water equivalent (SWE) elevation gradients at both sites; continental Gulkana Glacier's SWE gradient averaged 115&thinsp;mm 100&thinsp;m−1 and maritime Wolverine Glacier's gradient averaged 440&thinsp;mm 100&thinsp;m−1 (over &gt;&thinsp;1000&thinsp;m). We extrapolated GPR point observations across the glacier surface using terrain parameters derived from digital elevation models as predictor variables in two statistical models (stepwise multivariable linear regression and regression trees). Elevation and proxies for wind redistribution had the greatest explanatory power, and exhibited relatively time-constant coefficients over the study period. Both statistical models yielded comparable estimates of glacier-wide average SWE (1&thinsp;% average difference at Gulkana, 4&thinsp;% average difference at Wolverine), although the spatial distributions produced by the models diverged in unsampled regions of the glacier, particularly at Wolverine. In total, six different methods for estimating the glacier-wide winter balance average agreed within ±11&thinsp;%. We assessed interannual variability in the spatial pattern of snow accumulation predicted by the statistical models using two quantitative metrics. Both glaciers exhibited a high degree of temporal stability, with ∼85&thinsp;% of the glacier area experiencing less than 25&thinsp;% normalized absolute variability over this 5-year interval. We found SWE at a sparse network (3 stakes per glacier) of long-term glaciological stake sites to be highly correlated with the GPR-derived glacier-wide average. We estimate that interannual variability in the spatial pattern of winter SWE accumulation is only a small component (4&thinsp;%–10&thinsp;% of glacier-wide average) of the total mass balance uncertainty and thus, our findings support the concept that sparse stake networks effectively measure interannual variability in winter balance on glaciers, rather than some temporally varying spatial pattern of snow accumulation.</p