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

Why the idea of framework propositions cannot contribute to an understanding of delusions

One of the tasks that recent philosophy of psychiatry has taken upon itself is to extend the range of understanding to some of those aspects of psychopathology that Jaspers deemed beyond its limits. Given the fundamental difficulties of offering a literal interpretation of the contents of primary delusions, a number of alternative strategies have been put forward including regarding them as abnormal versions of framework propositions described by Wittgenstein in On Certainty. But although framework propositions share some of the apparent epistemic features of primary delusions, their role in partially constituting the sense of inquiry rules out their role in helping to understand delusions

The West Falmouth oil spill : persistence of the pollution eight months after the accident

A spill of 650,000-700,000 liters of #2 fuel oil has contaminated the coastal areas of Buzzards Bay, Mass. The present report summarizes the results of our continuing chemical and biological study which were available at the end of May 1970, more than eight months after the accident. The effects of environmental exposure on the composition of the oil are discussed; many analytical parameters are sufficiently stable to permit continued correlation of the oil remaining in sediments and organisms with the fuel oil involved in the spill. Oil from the spill is still present in the sediments, inshore and offshore and in the shellfish. A further spread of the pollution to more distant offshore regions has occurred during midwinter; as a result, the pollution now covers a much larger area than immediately after the accident. The first stages of biological (presumably bacterial) degradation of the oil are now evident especially in the least polluted regions; however, it has depleted predominantely the straight and branched chain alkanes. The more toxic aromatic hydrocarbons are resistant; as a result, the toxicity of the oil has not been diminished. Where oil can be detected in the sediments there has been a kill of animals; in the most polluted areas the kill has been almost total. Shellfish that survived the accident have taken up the fuel oil. The 1970 crop of shellfish is as heavily polluted as was last year’s crop. Oysters transplanted to unpolluted water for as long as 6 months retained the oil without change in composition or concentration.Submitted to the Office of Naval Research under Contract ONR N00014-66-C0241; NR 083-0043 and partially supported by the Federal Water Quality Act Grant 18050-EBN3 and with the National Science Foundation Grant GA-1625

From oil field to geothermal reservoir: assessment for geothermal utilization of two regionally extensive Devonian carbonate aquifers in Alberta, Canada

The Canadian province of Alberta has one of the highest per capita CO2-equivalent emissions in Canada, predominantly due to the industrial burning of coal for the generation of electricity and mining operations in the oil sands deposits. Alberta's geothermal potential could reduce CO2 emissions by substituting at least some fossil fuels with geothermal energy.The Upper Devonian carbonate aquifer systems within the Alberta Basin are promising target formations for geothermal energy. To assess their geothermal reservoir potential, detailed knowledge of the thermophysical and petrophysical rock properties is needed. An analogue study was conducted on two regionally extensive Devonian carbonate aquifers, the Southesk-Cairn Carbonate Complex and the Rimbey-Meadowbrook Reef Trend, to furnish a preliminary assessment of the potential for geothermal utilization. Samples taken from outcrops were used as analogues to equivalent formations in the reservoir and correlated with core samples of the reservoir. Analogue studies enable the determination and correlation of facies-related rock properties to identify sedimentary, diagenetic, and structural variations, allowing for more reliable reservoir property prediction.Rock samples were taken from several outcrops of Upper Devonian carbonates in the Rocky Mountain Front Ranges and from four drill cores from the stratigraphically equivalent Leduc Formation and three drill cores of the slightly younger Nisku Formation in the subsurface of the Alberta Basin. The samples were analyzed for several thermophysical and petrophysical properties, i.e., thermal conductivity, thermal diffusivity, and heat capacity, as well as density, porosity, and permeability. Furthermore, open-file petrophysical core data retrieved from the AccuMap database were used for correlation.The results from both carbonate complexes indicate good reservoir conditions regarding geothermal utilization with an average reservoir porosity of about 8&thinsp;%, average reservoir permeability between 10−12 and 10−15&thinsp;m2, and relatively high thermal conductivities ranging from 3 to 5&thinsp;W m−1 K−1. The most promising target reservoirs for hydrothermal utilisation are the completely dolomitized reef sections. The measured rock properties of the Leduc Formation in the subsurface show no significant differences between the Rimbey-Meadowbrook Reef Trend and the Southesk-Cairn Carbonate Complex. Differences between the dolomitized reef sections of the examined Leduc and Nisku Formation are also minor to insignificant, whereas the deeper basinal facies of the Nisku Formation differs significantly.In contrast, the outcrop analogue samples have lower porosity and permeability, likely caused by low-grade metamorphism and deformation during the Laramide orogeny that formed the Rocky Mountains. As such, the outcrop analogues are not valid proxies for the buried reservoirs in the Alberta Basin.Taken together, all available data suggest that dolomitization enhanced the geothermal properties, but depositional patterns and other diagenetic events, e.g., fracturing, also played an important role.</p

Delusional beliefs and reason giving

Delusions are often regarded as irrational beliefs, but their irrationality is not sufficient to explain what is pathological about them. In this paper we ask whether deluded subjects have the capacity to support the content of their delusions with reasons, that is, whether they can author their delusional states. The hypothesis that delusions are characterised by a failure of authorship, which is a dimension of self knowledge, deserves to be empirically tested because (a) it has the potential to account for the distinction between endorsing a delusion and endorsing a framework belief; (b) it contributes to a philosophical analysis of the relationship between rationality and self knowledge; and (c) it informs diagnosis and therapy in clinical psychiatry. However, authorship cannot provide a demarcation criterion between delusions and other irrational belief states

ROXAS – an efficient and accurate tool to detect vessels in diffuse-porous species

Wood-anatomical parameters form a valuable archive to study past limitations on tree growth and act as a link between dendrochronology and ecophysiology. Yet, analysing these parameters is a time-consuming procedure and only few long chronologies exist. To increase measurement efficiency of wood-anatomical parameters, novel tools like the automated image-analysis system ROXAS were developed. So far, ROXAS has only been applied to measure large earlywood vessels in ring-porous species. In this study, we evaluate if ROXAS is also suitable for efficient and accurate detection and measurement of vessels in diffuse-porous European beech. To do so, we compared the outcome of ROXAS with that of the established measurement programme Image-Pro Plus in terms of efficiency and accuracy. The two methods differed substantially in efficiency with automatic measurements using ROXAS being 19 times faster than with Image-Pro Plus. Although the procedures led to similar patterns in annual variation of mean vessel area and vessel density, the absolute values differed. Image-Pro Plus measured systematically lower mean vessel areas and higher vessel densities than ROXAS. This was attributed to the species-specific technical settings in ROXAS, leading to more realistic results than those obtained using the default settings in Image-Pro Plus. A shortcoming of ROXAS was, however, that small vessels

Results and Consequences of Magnet Test and Cosmic Challenge of the CMS Barrel Muon Alignment System

In the last year - as part of the first test of the CMS experiment at CERN [1] called Magnet Test and Cosmic Challenge (MTCC) - about 25% of the barrel muon position monitoring system was built and operated. The configuration enabled us to test all the elements of the system and its function in real conditions. The correct operation of the system has been demonstrated. About 500 full measurement cycles have been recorded. In the paper the setup –including the read-out and control - is described and the first preliminary results are presented

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

Outcrop analogue study to determine reservoir properties of the Los Humeros and Acoculco geothermal fields, Mexico

The Los Humeros geothermal system is steam dominated and currently under exploration with 65 wells (23 producing). Having temperatures above 380 ∘C, the system is characterized as a super hot geothermal system (SHGS). The development of such systems is still challenging due to the high temperatures and aggressive reservoir fluids which lead to corrosion and scaling problems. The geothermal system in Acoculco (Puebla, Mexico; so far only explored via two exploration wells) is characterized by temperatures of approximately 300 ∘C at a depth of about 2 km. In both wells no geothermal fluids were found, even though a well-developed fracture network exists. Therefore, it is planned to develop an enhanced geothermal system (EGS). For better reservoir understanding and prospective modeling, extensive geological, geochemical, geophysical and technical investigations are performed within the scope of the GEMex project. Outcrop analogue studies have been carried out in order to identify the main fracture pattern, geometry and distribution of geological units in the area and to characterize all key units from the basement to the cap rock regarding petro- and thermo-physical rock properties and mineralogy. Ongoing investigations aim to identify geological and structural heterogeneities on different scales to enable a more reliable prediction of reservoir properties. Beside geological investigations, physical properties of the reservoir fluids are determined to improve the understanding of the hydrochemical processes in the reservoir and the fluid-rock interactions, which affect the reservoir rock properties