Systematic screening for novel, serologically reactive Hepatitis E Virus epitopes

<p>Abstract</p> <p>Background</p> <p>The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats.</p> <p>Methods</p> <p>From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis.</p> <p>Results</p> <p>HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens.</p> <p>Conclusions</p> <p>The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.</p

Strategien und Technologien einer pluralistischen Fern- und Nahwärmeversorgung in einem liberalisierten Energiemarkt unter besonderer Berücksichtigung der Kraft-Wärme-Kopplung und regenerativer Energien : Kurztitel: Pluralistische Wärmeversorgung ; AGFW-Hauptstudie - erster Bearbeitungsabschnitt. Band 1, Grundlagen der Kraft-Wärme-Kopplung, Zertifizierungsverfahren und Fördermodelle

Die im vorliegenden Band 1 vorgestellten Ergebnisse sollen der Begleitung der anstehenden KWK-Gesetzgebung in technischer und wirtschaftlicher Hinsicht dienen. Das derzeitige KWK-(Vorschalt-)Gesetz, welches durch ein neues mit klareren Kriterien verbundenes Gesetz ersetzt werden soll, ist in mehrfacher Hinsicht problematisch, da es Regelungen zum Auffangen von Stranded Investments mit Regelungen zur Förderung von KWK vermischt, keine klare Definition von KWK enthält, industrielle KWK ausgegrenzt und durch die intransparente Förderstruktur das Mittelaufkommen und die Mittelverwendung nicht nachvollziehbar macht. Ein KWK-Ausbau wird sich in der gegenwärtigen Situation des Strommarktes nur auf der Basis einer Förderung entwickeln können (vgl. Vorstudie). Obwohl neue KWK-Anlagen im Vergleich zu neuen Anlagen der ungekoppelten Erzeugung unter Vollkostenbedingungen meist günstiger abschneiden, benötigen sie vor dem Hintergrund des aktuell auf dem Niveau kurzfristiger Grenzkosten geführten Preiskampfes zusätzliche Deckungsbeiträge. Die Analyse der Vielzahl vorgeschlagener Zertifizierungskriterien hat ergeben, dass definierter KWK-Strom eine geeignete Messgröße darstellt. Ausführliche Analysen zeigen, dass die Bestimmung dieses Stromanteils mit Hilfe einer einmaligen Anlagenzertifizierung relativ unproblematisch ist. Eine weitere Differenzierung des so definierten KWK-Stroms, z. B. hinsichtlich der CO2-Effizienz, birgt dagegen die Gefahr so krasser Fördergegensätze zwischen alten und neuen Anlagen sowie zwischen gas- und kohlegefeuerten Anlagen, dass dadurch vorhandene, für zukünftige Anwendungen prädestinierte Standorte verloren gehen könnten und die sinnvolle Auskopplung großer Wärmemengen aus Steinkohlekraftwerken unterbleibt. Die Bewertung verschiedener Fördermodelle ergibt kein eindeutiges Bild, welches Fördermodell zu bevorzugen wäre. Andererseits zeigt sich, dass sich aus allen Bausteinen von Förderinstrumenten ein sinnvolles Instrumentenmix konstruieren lässt

Genome-wide association for milk production and lactation curve parameters in Holstein dairy cows

The aim of this study was to identify genomic regions associated with 305-day milk yield and lactation curve parameters on primiparous (n = 9,910) and multiparous (n = 11,158) Holstein cows. The SNP solutions were estimated using a weighted single-step genomic BLUP approach and imputed high-density panel (777k) genotypes. The proportion of genetic variance explained by windows of 50 consecutive SNP (with an average of 165 Kb) was calculated, and regions that accounted for more than 0.50% of the variance were used to search for candidate genes. Estimated heritabilities were 0.37, 0.34, 0.17, 0.12, 0.30 and 0.19, respectively, for 305-day milk yield, peak yield, peak time, ramp, scale and decay for primiparous cows. Genetic correlations of 305-day milk yield with peak yield, peak time, ramp, scale and decay in primiparous cows were 0.99, 0.63, 0.20, 0.97 and -0.52, respectively. The results identified three windows on BTA14 associated with 305-day milk yield and the parameters of lactation curve in primi- and multiparous cows. Previously proposed candidate genes for milk yield supported by this work include GRINA, CYHR1, FOXH1, TONSL, PPP1R16A, ARHGAP39, MAF1, OPLAH and MROH1, whereas newly identified candidate genes are MIR2308, ZNF7, ZNF34, SLURP1, MAFA and KIFC2 (BTA14). The protein lipidation biological process term, which plays a key role in controlling protein localization and function, was identified as the most important term enriched by the identified genes

Expert-based development of a generic HACCP-based risk management system to prevent critical negative energy balance in dairy herds

The objective of this study was to develop a generic risk management system based on the Hazard Analysis and Critical Control Point (HACCP) principles for the prevention of critical negative energy balance (NEB) in dairy herds using an expert panel approach. In addition, we discuss the advantages and limitations of the system in terms of implementation in the individual dairy herd. For the expert panel, we invited 30 researchers and advisors with expertise in the field of dairy cow feeding and/or health management from eight European regions. They were invited to a Delphi-based set-up that included three inter-correlated questionnaires in which they were asked to suggest risk factors for critical NEB and to score these based on 'effect' and 'probability'. Finally, the experts were asked to suggest critical control points (CCPs) specified by alarm values, monitoring frequency and corrective actions related to the most relevant risk factors in an operational farm setting. A total of 12 experts (40 %) completed all three questionnaires. Of these 12 experts, seven were researchers and five were advisors and in total they represented seven out of the eight European regions addressed in the questionnaire study. When asking for suggestions on risk factors and CCPs, these were formulated as 'open questions', and the experts' suggestions were numerous and overlapping. The suggestions were merged via a process of linguistic editing in order to eliminate doublets. The editing process revealed that the experts provided a total of 34 CCPs for the 11 risk factors they scored as most important. The consensus among experts was relatively high when scoring the most important risk factors, while there were more diverse suggestions of CCPs with specification of alarm values and corrective actions. We therefore concluded that the expert panel approach only partly succeeded in developing a generic HACCP for critical NEB in dairy cows. We recommend that the output of this paper is used to inform key areas for implementation on the individual dairy farm by local farm teams including farmers and their advisors, who together can conduct herd-specific risk factor profiling, organise the ongoing monitoring of herd-specific CCPs, as well as implement corrective actions when CCP alarm values are exceeded

Search for Bs0B^{0}_{s} oscillations using inclusive lepton events

A search for Bs oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the prop er time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to Bs mixing is obtained by identifying subsamples of events having a Bs purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Dms>9.5 ps-1 at 95% CL. Combining with the ALEPH Ds based analyses yields Dms>9.6 ps-1 at 95% CL.A search for B0s oscillations is performed using a sample of semileptonic b-hadron decays collected by the ALEPH experiment during 1991-1995. Compared to previous inclusive lepton analyses, the proper time resolution and b-flavour mistag rate are significantly improved. Additional sensitivity to B0s mixing is obtained by identifying subsamples of events having a B0s purity which is higher than the average for the whole data sample. Unbinned maximum likelihood amplitude fits are performed to derive a lower limit of Deltam_s>9.5ps^-1 at 95% CL. Combining with the ALEPH D-s based analyses yields Deltam_s>9.6ps^-1 at 95% CL

Measurement of the tau lepton lifetime

The mean lifetime of the tau lepton is measured in a sample of 25700 tau pairs collected in 1992 with the ALEPH detector at LEP. A new analysis of the 1-1 topology events is introduced. In this analysis, the dependence of the impact parameter sum distribution on the daughter track momenta is taken into account, yielding improved precision compared to other impact parameter sum methods. Three other analyses of the one- and three-prong tau decays are updated with increased statistics. The measured lifetime is 293.5+/-3.1+/-1.7 fs. Including previous (1989-1991) ALEPH measurements, the combined tau lifetime is 293.7+/-2.7+/-1.6 fs