Hepatocyte KLF6 expression affects FXR signalling and the clinical course of primary sclerosing cholangitis

Background & Aims: Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel-like-factor-6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data are yet available on its potential role in cholestasis. Here, we aimed to identify the impact of hepatic KLF6 expression on cholestatic liver injury and PSC and identify potential effects on farnesoid-X-receptor (FXR) signalling. Methods: Hepatocellular KLF6 expression was quantified by immunohistochemistry (IHC) in liver biopsies of PSC patients and correlated with serum parameters and clinical outcome. Liver injury was analysed in hepatocyte-specific Klf6-knockout mice following bile duct ligation (BDL). Chromatin-immunoprecipitation-assays (ChIP) and KLF6-overexpressing HepG2 cells were used to analyse the interaction of KLF6 and FXR target genes such as NR0B2. Results: Based on IHC, PSC patients could be subdivided into two groups showing either low (80%) hepatocellular KLF6 expression. In patients with high KLF6 expression, we observed a superior survival in Kaplan-Meier analysis. Klf6-knockout mice showed reduced hepatic necrosis following BDL when compared to controls. KLF6 suppressed NR0B2 expression in HepG2 cells mediated through binding of KLF6 to the NR0B2 promoter region. Conclusion: Here, we show an association between KLF6 expression and the clinical course and overall survival in PSC patients. Mechanistically, we identified a direct interaction of KLF6 with the FXR target gene NR0B2

The water electrolysis Hall effect Thruster

This study proposes operating a Hall effect Thruster (HET) on the products of in-situ water electrolysis. Oxygen is supplied to the anode and hydrogen to the cathode to mitigating poisoning. In comparison to other alternative HET propellants water is non-toxic, low cost, highly storable, and allows synergies with chemical propulsion systems. The competitiveness of this concept is experimentally tested by simulating, designing, constructing, and operating a thruster optimised for oxygen: the Water ElecTrolysis Hall Effect Thruster (WET-HET). A zero-dimensional particle-in-cell code is used to optimise the device, resulting in a channel width of 5 mm, outer circumference of 25 mm and depth ranging from 35 mm to 60 mm. Iterative magnetic, thermal, and mechanical modelling finalises the design. A hanging pendulum style thrust balance is used to directly measure WET-HET performance. Safety restrictions require krypton rather than hydrogen be used for the cathode. The WET-HET is tested on discharge powers up to 3200 W and oxygen mass flow rates ranging from 0.99 mg/s to 1.85 mg/s. Three different channel depths are tested: 35 mm, 45 mm and 60 mm. The WET-HET is characterised for a range of different magnetic field strengths and for three distinct magnetic topologies. Two channel wall materials were investigated: alumina and boron nitride. The highest thrust measured was 38.63±0.25 mN, with a maximum specific impulse of 4112±36 s and a maximum anode thrust efficiency of 24.4±5.9%. This optimum was found when the WET-HET was operated at 3200 W discharge power, 0.99 mg/s mass flow rate, 35 mm channel depth and a magnetic field that peaked near 600 Gauss. Boron nitride outperformed alumina by approximately 40%. Contrary to expectation, increasing the axial thickness of the magnetic region had little impact on discharge voltage, but led to a reduction in thrust, specific impulse, and thrust efficiency of the device.Open Acces

Experimental investigation of a water electrolysis Hall effect thruster

We conceptualise an electric propulsion system in which water is utilised as a propellant for a Hall effect thruster using in situ electrolysis. By supplying the generated oxygen to the thruster anode and the hydrogen to the neutralising cathode, poisoning of the cathode emitters is mitigated. Not only does such a system benefit from the low cost, high storability and in situ resource utilisation potential of water, but synergies with water electrolysis chemical propulsion systems allow for multi-mode chemical-electrical propulsion architectures. The water electrolysis Hall effect thruster (WET-HET) has been optimised to operate on oxygen as a proof of this concept. We perform direct thrust measurements on the WET-HET using a hanging pendulum thrust balance. The thruster was operated using oxygen mass flow rates ranging from 0.96 mg s−1 to 1.85 mg s−1, and discharge powers ranging from 490 W to 2880 W. The cathode used in this test was supplied with krypton rather than hydrogen, due to laboratory restrictions preventing compressed hydrogen and oxygen cylinders being used in close proximity. Two channel wall materials were investigated — alumina and boron nitride. It was found that the wall material had a significant impact on the thrust, with an increase of approximately 40% for boron nitride. Reconfiguration of the magnetic components of the WET-HET allows us to alter the thickness of the magnetised region within the thruster channel. We test the device in three different magnetic configurations, ranging from a traditionally thin magnetic region to complete magnetisation of the discharge channel. We find that increasing the thickness of the magnetic region reduces thrust, specific impulse, and thrust efficiency of the device. We assess the change in performance as we change the discharge channel depth of the thruster. The best performance was achieved with the shallowest channel of depth 35 mm. We find the that thrust, specific impulse and anode thrust efficiency increases linearly with power for all configurations with no obvious plateau. Greatest specific impulse and efficiency was found when mass flow was lowest. Although discharge voltage increases linearly with magnetic field strength, thrust, specific impulse and efficiency peaks at 480 Gauss. The greatest thrust measured was 38.63 ± 0.25 mN, with a maximum specific impulse of 4112 ± 36 s and a maximum anode thrust efficiency of 15.50 ± 0.27%

Low power thrust measurements of the water electrolysis Hall effect thruster

We propose that a Hall effect thruster could be modified to operate on the products of water electrolysis. Such a thruster would exploit the low cost and high storability of water while producing gaseous hydrogen and oxygen in-situ as they are required. By supplying the anode with oxygen and the cathode with hydrogen, the poisoning of the cathode is mitigated. The water electrolysis Hall effect thruster (WET-HET) has been designed to demonstrate this concept. The dimensions of the WET-HET have been optimized for oxygen operation using PlasmaSim, a zero-dimensional particle in cell code. We present the first direct thrust measurements of the WET-HET. A hanging pendulum style thrust balance is used to measure the thrust of the WET-HET while operating in the Boltzmann vacuum facility within the Imperial Plasma Propulsion Laboratory. For this test the beam was neutralized using a filament plasma bridge neutralizer operating on krypton. We find thrust, specific impulse, and thrust efficiency all increase linearly with power for values between 400 and 1050 W. Increasing the mass flow rate from 0.96 to 1.85 mg/s increases thrust at the expense of specific impulse. Changing mass flow rate was found to have little impact on the thrust efficiency over this range. An optimal radial magnetic flux density of 403 G at the exit plane is found. Further increases to the magnetic field beyond this point were found to decrease the thrust, specific impulse and thrust efficiency, whereas the discharge voltage increased monotonically with increasing magnetic field for a given input power. It was found that the experimental thruster performance was lower than the simulation results from PlasmaSim. However, the general trends in performance as a function of power and propellant mass flow rate were preserved. We attribute a portion of this discrepancy to the inability of the simulation to model the energy absorbed by the covalent bond of the oxygen molecule. For the powers and mass flow rates surveyed we measured thrust ranging from 4.52±0.18 to 8.45±0.18mN, specific impulse between 324±12 and 593±12s, and anode thrust efficiencies between 1.34±0.10 and 2.34±0.10%

Corpus cultus Iovis Dolicheni (CCID) /

Errata slip inserted.Includes indexes.Includes bibliographical references (p. xvii-xxiv).Preliminary material -- SYRIA, MESOPOTAMIA, ASIA MINOR -- GRAECIA, MACEDONIA, THRACIA -- MOESIA INFERIOR -- MOESIA SUPERIOR -- DALMATIA -- DACIA -- PANNONIA INFERIOR -- PANNONIA SUPERIOR -- NORICUM -- ROM -- ITALIA -- RAETIA -- GERMANIA SUPERIOR -- GERMANIA INFERIOR -- BRITANNIA -- GALLIA -- HISPANIA -- AFRICA -- ADDENDA -- KONKORDANZEN -- INDICES -- TAFELVERZEICHNIS -- TAFELN I-CXXXIII