Different Outcomes of Experimental Hepatitis E Virus Infection in Diverse Mouse Strains, Wistar Rats, and Rabbits

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but autochthonous cases of zoonotic genotype 3 (HEV-3) infection also occur in industrialized countries. In contrast to swine, rats, and rabbits, natural HEV infections in mice have not yet been demonstrated. The pig represents a well-established large animal model for HEV-3 infection, but a suitable small animal model mimicking natural HEV-3 infection is currently missing. Therefore, we experimentally inoculated C57BL/6 mice (wild-type, IFNAR−/−, CD4−/−, CD8−/−) and BALB/c nude (nu/nu) mice, Wistar rats, and European rabbits with a wild boar-derived HEV-3 strain and monitored virus replication and shedding, as well as humoral immune responses. HEV RNA and anti-HEV antibodies were detected in one and two out of eight of the rats and all rabbits inoculated, respectively, but not in any of the mouse strains tested. Remarkably, immunosuppressive dexamethasone treatment of rats did not enhance their susceptibility to HEV infection. In rabbits, immunization with recombinant HEV-3 and ratHEV capsid proteins induced protection against HEV-3 challenge. In conclusion, the rabbit model for HEV-3 infection may serve as a suitable alternative to the non-human primate and swine models, and as an appropriate basis for vaccine evaluation studies

Normative Data and Minimally Detectable Change for Inner Retinal Layer Thicknesses Using a Semi-automated OCT Image Segmentation Pipeline

Neurodegenerative and neuroinflammatory diseases regularly cause optic nerve and retinal damage. Evaluating retinal changes using optical coherence tomography (OCT) in diseases like multiple sclerosis has thus become increasingly relevant. However, intraretinal segmentation, a necessary step for interpreting retinal changes in the context of these diseases, is not standardized and often requires manual correction. Here we present a semi-automatic intraretinal layer segmentation pipeline and establish normative values for retinal layer thicknesses at the macula, including dependencies on age, sex, and refractive error. Spectral domain OCT macular 3D volume scans were obtained from healthy participants using a Heidelberg Engineering Spectralis OCT. A semi-automated segmentation tool (SAMIRIX) based on an interchangeable third-party segmentation algorithm was developed and employed for segmentation, correction, and thickness computation of intraretinal layers. Normative data is reported froma 6mmEarly Treatment Diabetic Retinopathy Study (ETDRS) circle around the fovea. An interactive toolbox for the normative database allows surveying for additional normative data. We cross-sectionally evaluated data from218 healthy volunteers (144 females/74males, age 36.5 ± 12.3 years, range 18–69 years). Average macular thickness (MT) was 313.70 ± 12.02 μm, macular retinal nerve fiber layer thickness (mRNFL) 39.53 ± 3.57 μm, ganglion cell and inner plexiform layer thickness (GCIPL) 70.81 ± 4.87 μm, and inner nuclear layer thickness (INL) 35.93 ± 2.34 μm. All retinal layer thicknesses decreased with age. MT and GCIPL were associated with sex, with males showing higher thicknesses. Layer thicknesses were also positively associated with each other. Repeated-measurement reliability for the manual correction of automatic intraretinal segmentation results was excellent, with an intra-class correlation coefficient >0.99 for all layers. The SAMIRIX toolbox can simplify intraretinal segmentation in research applications, and the normative data application may serve as an expandable reference for studies, in which normative data cannot be otherwise obtained

Oscillation frequencies and mode lifetimes in alpha Centauri A

We analyse our recently-published velocity measurements of alpha Cen A (Butler et al. 2004). After adjusting the weights on a night-by-night basis in order to optimize the window function to minimize sidelobes, we extract 42 oscillation frequencies with l=0 to 3 and measure the large and small frequency separations. We give fitted relations to these frequencies that can be compared with theoretical models and conclude that the observed scatter about these fits is due to the finite lifetimes of the oscillation modes. We estimate the mode lifetimes to be 1-2 d, substantially shorter than in the Sun.Comment: Accepted by Ap

Multi-nuclear, high-pressure, operando FlowNMR spectroscopic study of Rh/PPh3 – catalysed hydroformylation of 1-hexene

The hydroformylation of 1-hexene with 12 bar of 1 : 1 H2/CO in the presence of the catalytic system [Rh(acac)(CO)2]/PPh3 was successfully studied by real-time multinuclear high-resolution FlowNMR spectroscopy at 50 °C. Quantitative reaction progress curves that yield rates as well as chemo- and regioselectivities have been obtained with varying P/Rh loadings. Dissolved H2 can be monitored in solution to ensure true operando conditions without gas limitation. 31P{1H} and selective excitation 1H pulse sequences have been periodically interleaved with 1H FlowNMR measurements to detect Rh–phosphine intermediates during the catalysis. Stopped-flow experiments in combination with diffusion measurements and 2D heteronuclear correlation experiments showed the known tris-phosphine complex [RhH(CO)(PPh3)3] to generate rapidly exchanging isomers of the bis-phosphine complex [Rh(CO)2(PPh3)2] under CO pressure that directly enter the catalytic cycle. A new mono-phosphine acyl complex has been identified as an in-cycle reaction intermediate

Constrained Willmore Surfaces

Constrained Willmore surfaces are conformal immersions of Riemann surfaces that are critical points of the Willmore energy $W=\int H^2$ under compactly supported infinitesimal conformal variations. Examples include all constant mean curvature surfaces in space forms. In this paper we investigate more generally the critical points of arbitrary geometric functionals on the space of immersions under the constraint that the admissible variations infinitesimally preserve the conformal structure. Besides constrained Willmore surfaces we discuss in some detail examples of constrained minimal and volume critical surfaces, the critical points of the area and enclosed volume functional under the conformal constraint.Comment: 17 pages, 8 figures; v2: Hopf tori added as an example, minor changes in presentation, numbering changed; v3: new abstract and appendix, several changes in presentatio

An experiment for the measurement of the bound-beta decay of the free neutron

The hyperfine-state population of hydrogen after the bound-beta decay of the neutron directly yields the neutrino left-handedness or a possible right-handed admixture and possible small scalar and tensor contributions to the weak force. Using the through-going beam tube of a high-flux reactor, a background free hydrogen rate of ca. 3 s$^{-1}$ can be obtained. The detection of the neutral hydrogen atoms and the analysis of the hyperfine states is accomplished by Lamb shift source type quenching and subsequent ionization. The constraints on the neutrino helicity and the scalar and tensor coupling constants of weak interaction can be improved by a factor of ten.Comment: 9 pages, 5 figures. Submitted to EPJ

Zwischenbericht zum Projekt 'FPGA-Entwurfssystem: Test und Integration von Synthese- und Layoutwerkzeugen für den FPGA-Entwurf

Seit einigen Jahren werden für den Entwurf anwendungsspezifischer Schaltungen verstärkt Field-Programmable Gate-Arrays (FPGAs) als Alternative zu maskenprogrammierten ASICs eingesetzt. Der Vorteil von FPGAs liegt vor allem in der schnellen und preiswerten Schaltungsentwicklung. Für den Entwurf von Schaltungen sind derzeit jedoch Software-Werkzeuge verschiedener Hersteller erforderlich. Im Rahmen eines von der Deutschen Forschungsgemeinschaft geförderten Projektes wurde gemeinsam mit der Universität Tübingen und der Technischen Universität München ein funktionsfähiges FPGA-Entwurfssystem entwickelt. Das in diesem Bericht vorgestellte Entwurfssystem beinhaltet alle wichtigen Synthese- und Layout-Komponenten zur Realisierung von Schaltungen auf FPGAs. Es wird eine Entwurfsmethodik vorgestellt, mit der alle notwendigen Entwurfsschritte bis zur Verdrahtung durchführbar sind. Ausgangspunkt ist dabei eine Schaltungsbeschreibung in verhaltensbasiertem VHDL. Für die einzelnen Systemkomponenten werden Software-Werkzeuge verwendet, die an den beteiligten Instituten entwickelt werden. Zur Ablaufsteuerung wurde eine Benutzeroberfläche entworfen, in die bisher die Technologieabbildung sowie das Layout integriert wurden

Ein Branch&Bound-Ansatz zur Verdrahtung von Field Programmable Gate-Arrays

Zur Verdrahtung der meisten FPGA-Architekturen können die aus dem ASIC-Entwurf stammenden Werkzeuge wie z.B. Kanalverdrahter nicht eingesetzt werden. Eine vollautomatische Verdrahtung mit optimalen Signallaufzeiten kann nur dann erreicht werden, wenn bei gegebener Plazierung die Leitungführung den technologischen Gegebenheiten angepaßt wird. Diese unterscheiden sich deutlich von denen in ASICs. Im Rahmen des von der Deutschen Forschungsgemeinschaft (DFG) geförderten Gemeinschafts-Projekts „FPGA Entwurfssystem“, an dem die Universität Leipzig, die Universität Tübingen und die Technischen Universität München beteiligt sind, wurden am Lehrstuhl für Computersysteme (Prof. W.G. Spruth) des Instituts für Informatik der Universität Leipzig Verfahren zur effizienten und qualitativ hochwertigen Verdrahtung von FPGA-Bausteinen entwickelt. Es wird eine Beschreibung des Verdrahtungsproblems für FPGAs gegeben und ein Lösungsansatz mit Hilfe des Branch&Bound – Verfahrens vorgestellt. Die Ergebnisse in Form von Programmlaufzeiten, Länge des kritischen Pfades und Anzahl der betrachteten Suchknoten in Abhängigkeit von einer Vielzahl von Schaltungsvarianten sind tabellarisch dargestellt und dokumentieren eine deutliche Verkürzung der längsten Pfade gegenüber dem Plazier- und Verdrahtungswerkzeug von Xilinx. Abschließend werden Probleme und weiterführende Arbeiten diskutiert