A frequent variant in the human bile salt export pump gene ABCB11 is associated with hepatitis C virus infection, but not liver stiffness in a German population

Background: The human ATP-binding cassette, subfamily B, member 11 (ABCB11) gene encodes the bile salt export pump, which is exclusively expressed at the canalicular membrane of hepatocytes. A frequent variant in the coding region, c.1331 T > C, leading to the amino acid exchange p.V444A, has been associated with altered serum bile salt levels in healthy individuals and predisposes homozygous carriers of the [C] allele for obstetric cholestasis. Recently, elevated bile salt levels were shown to be significantly associated with rates and risk of cirrhosis in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon-alpha2 and ribavirin, suggesting a potential role for bile salt levels in HCV treatment outcomes and in the fibrogenic evolution of HCV-related liver disease. The aim of this study was to investigate a possible association of ABCB11 c.1331 T > C with hepatitis C virus (HCV) infection and fibrosis stages as assessed by non-invasive transient elastography in a German cohort of patients. Methods: ABCB11 c.1331 T > C genotype was determined by allelic discrimination assay in 649 HCV infected cases and 413 controls. Overall, 444 cases were staged for fibrotic progression by measurement of liver stiffness. Results: Homo- or heterozygous presence of the frequent [C] allele was associated with HCV positivity (OR = 1.41, CI = 1.02 - 1.95, p = 0.037). No association was detectable between the ABCB11 c.1331 T > C genotype and increased liver stiffness. Conclusions: Our data confirm that homozygous presence of the major [C] allele of ABCB11 c.1331 T > C is a genetic susceptibility factor for HCV infection, but not for liver fibrosis

Nuclear Receptor Variants in Liver Disease

This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment

SAsSy – Scrutable Autonomous Systems

Abstract. An autonomous system consists of physical or virtual systems that can perform tasks without continuous human guidance. Autonomous systems are becoming increasingly ubiquitous, ranging from unmanned vehicles, to robotic surgery devices, to virtual agents which collate and process information on the internet. Existing autonomous systems are opaque, limiting their usefulness in many situations. In order to realise their promise, techniques for making such autonomous systems scrutable are therefore required. We believe that the creation of such scrutable autonomous systems rests on four foundations, namely an appropriate planning representation; the use of a human understandable reasoning mechanism, such as argumentation theory; appropriate natural language generation tools to translate logical statements into natural ones; and information presentation techniques to enable the user to cope with the deluge of information that autonomous systems can provide. Each of these foundations has its own unique challenges, as does the integration of all of these into a single system.

Secondary comminution of wood pellets in power plant and laboratory-scale mills

peer-reviewedThe full text of this article will not be available in ULIR until the embargo expires on the 14/03/2019This study aims to determine the influence of mill type and pellet wood composition on particle size and shape of milled wood. The size and shape characteristics of pellets comminuted using power plant roller mills were compared with those obtained by using laboratory-scale roller- and hammer mills. A 2D dynamic imaging device was used for particle characterization. It was shown that mill type has a significant impact on particle size but an almost negligible effect on the shape of milled wood. Comminution in the pilot plant using a Loesche roller mill requires less energy than using a hammer mill, but generates a larger fraction of coarse particles. The laboratory-scale roller mill provides comparable results with the power plant roller mill with respect to particle size and shape

International order and the pain of negativity : Hegel’s political theology

Defence date: 03 November 2023Examining board: Prof. Nehal Bhuta, (University of Edinburgh; European University Institute, external supervisor); Prof. Nicolas Guilhot, (European University Institute); Prof. Frank Ruda, (University of Dundee); Prof. Samuel Moyn, (Yale University)This thesis argues that an immanent critique of Hegel can offer a utopian alternative to contemporary theories of international law. Preoccupied with either solving seemingly ahistorical problems by copy-pasting concepts from the domestic liberal toolset or deconstructing the false universalisms underpinning this liberal order, lawyers struggle to grasp international law in the framework of a transformative project. I show how Hegel, in a paradoxically sceptical fashion, recovers absolute knowledge, the necessary corollary of universal emancipation, against the foil of his liberal and conservative opponents who abandoned both quests. The central argument of my thesis is that Hegel finds the experience content and actualisation of the absolute in the philosophical ‘sublation’ of Christian revelation. In the pain of negativity, the finite human spirit realises that its self-righteousness othered and killed God. Following an immanent critique of Hegel’s theory of grace, we can conceptualise the result of human spirit’s transformation into absolute spirit as vulnerable and ephemeral: whenever spirit cannot account for otherness, absolute spirit falls from grace and reverts into objective spirit’s selfabsorbedness. Hegel, however, neglected a great deal of otherness, that of women, the poor, and (colonised) slaves, without letting the modern Protestant Germanic spirit lose its world-historical primacy. I propose that we can go with Hegel beyond Hegel by searching for liberating agency in those whose ‘pain of negativity’ Hegel partially recognised. This turn to agents of liberation allows a critical reappraisal of a Hegelian voluntarist reading of international legal positivism. The state becomes the epistemologically necessary and normatively hopeful focal point only to the extent that it crystalises the identified agents’ historical struggles for self-determination. The role of positivism is to protect the spaces of the actuality of reason that are the historical results of these struggles and from which new, more transformative projects can arise

First Operation of a Resistive Shell Liquid Argon Time Projection Chamber -- A new Approach to Electric-Field Shaping

We present a new technology for the shaping of the electric field in Time Projection Chambers (TPCs) using a carbon-loaded polyimide foil. This technology allows for the minimisation of passive material near the active volume of the TPC and thus is capable to reduce background events originating from radioactive decays or scattering on the material itself. Furthermore, the high and continuous electric resistivity of the foil limits the power dissipation per unit area and minimizes the risks of damages in the case of an electric field breakdown. Replacing the conventional field cage with a resistive plastic film structure called 'shell' decreases the number of components within the TPC and therefore reduces the potential points of failure when operating the detector. A prototype liquid argon (LAr) TPC with such a resistive shell and with a cathode made of the same material was successfully tested for long term operation with electric field values up to about 1.5 kV/cm. The experiment shows that it is feasible to successfully produce and shape the electric field in liquefied noble-gas detectors with this new technology.Comment: 13 page

FATTY ACID COMPOSITION OF VEGETABLE OILS AND FATS

The main objective of this work was to identify the fatty acid composition of several vegetable oils and fats. Twenty vegetable oils and fats were analyzed for its fatty acid composition by gas chromatography (gc-fid). Among the evaluated oils the higher contents of saturated fatty acids were found in the coconut and palm fats, that showed above 80% of saturated fatty acids. Except palm fat, that presented about 50% in saturated fatty acids, all other oils showed saturated fatty acids below 25%, being the canola oil that presented the highest unsaturated fatty acid content. Furthermore, canola oil, in the same way soybean oil, showed between 8 and 10% of omega-3 fatty acids. The borage and evening primrose oils differed from the others by presenting appreciable amount of G-linolenic acid, and the linseed oil for presenting more than 50% in linolenic acid. The rice, peanut, cotton and corn oils showed higher content of oleic and linoleic acids.  O principal objetivo deste trabalho foi identificar a composição em ácidos graxos de diversos óleos e gorduras vegetais. Vinte óleos e gorduras vegetais foram avaliados quanto a composição em ácidos graxos por cromatografia a gás (GC-FID). Entre os óleos estudados, os maiores teores em ácidos graxos saturados foram encontrados nas gorduras de coco e de semente de palma, que apresentaram mais de 80% de ácidos graxos saturados. A exceção da gordura de palma, com cerca de 50% em ácidos graxos saturados, todos os outros óleos revelaram percentuais em ácidos graxos saturados abaixo de 25%, sendo o óleo de canola o que apresentou maior percentual em ácidos graxos insaturados. Além disso, o óleo de canola e de soja apresentaram entre 8 e 10% de ácido ômega-3. Os óleos de borragem e prímula diferenciaram-se dos demais pelas quantidades apreciáveis de ácido gama-linolênico, e o óleo de linhaça por apresentar mais de 50% em ácido linolênico. Os óleos de arroz, amendoim, algodão e de milho evidenciaram maiores percentuais dos ácidos graxos oléico e linoléico

Tissue engineering on matrix: future of autologous tissue replacement

Tissue engineering aims at the creation of living neo-tissues identical or close to their native human counterparts. As basis of this approach, temporary biodegradable supporter matrices are fabricated in the shape of a desired construct, which promote tissue strength and provide functionality until sufficient neo-tissue is formed. Besides fully synthetic polymer-based scaffolds, decellularized biological tissue of xenogenic or homogenic origin can be used. In a second step, these scaffolds are seeded with autologous cells attaching to the scaffold microstructure. In order to promote neo-tissue formation and maturation, the seeded scaffolds are exposed to different forms of stimulation. In cardiovascular tissue engineering, this "conditioning” can be achieved via culture media and biomimetic in vitro exposure, e.g., using flow bioreactors. This aims at adequate cellular differentiation, proliferation, and extracellular matrix production to form a living tissue called the construct. These living autologous constructs, such as heart valves or vascular grafts, are created in vitro, comprising a viable interstitium with repair and remodeling capabilities already prior to implantation. In situ further in vivo remodeling is intended to recapitulate physiological vascular architecture and function. The remodeling mechanisms were shown to be dominated by monocytic infiltration and chemotactic host-cell attraction leading into a multifaceted inflammatory process and neo-tissue formation. Key molecules of these processes can be integrated into the scaffold matrix to direct cell and tissue fate in viv