Molecular, Biochemical and Genetic Characteristics of BSE in Canada

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide

Prion protein-specific antibodies that detect multiple TSE agents with high sensitivity

This paper describes the generation, characterisation and potential applications of a panel of novel anti-prion protein monoclonal antibodies (mAbs). The mAbs were generated by immunising PRNP null mice, using a variety of regimes, with a truncated form of recombinant ovine prion protein spanning residues 94–233. Epitopes of specific antibodies were mapped using solid-phase Pepscan analysis and clustered to four distinct regions within the PrP molecule. We have demonstrated the utility of these antibodies by use of Western blotting and immunohistochemistry in tissues from a range of different species affected by transmissible spongiform encephalopathy (TSE). In comparative tests against extensively-used and widely-published, commercially available antibodies, similar or improved results can be obtained using these new mAbs, specifically in terms of sensitivity of detection. Since many of these antibodies recognise native PrPC, they could also be applied to a broad range of immunoassays such as flow cytometry, DELFIA analysis or immunoprecipitation. We are using these reagents to increase our understanding of TSE pathogenesis and for use in potential diagnostic screening assays

Ein mechatronisches Radkonzept zur aktiven Beeinflussung der Fahrdynamik von Schienenfahrzeugen

Es wird ein mechatronisches Radsatzkonzept vorgestellt, das es erlaubt, dem Radsatz zwischen beiden Rädern ein Relativmoment, das mit der relativen Verdrehung der Räder in Wechselwirkung steht, aktiv geregelt einzuprägen. Diese Methode ermöglicht sowohl die Erhöhung der Fahrstabilität bei hohen Geschwindigkeiten, als auch eine deutliche Verringerung von Reibleistung und Verschleiß im Gleisbogen. Damit kann der klassische Zielkonflikt bei der Fahrwerksauslegung zwischen Fahrstabilität und gutem Bogenlaufverhalten gelöst werden. Diese Möglichkeiten werden anhand von Simulationsrechnungen und Ergebnissen aus Experimenten, die an einem zweiachsigen Fahrzeug im Maßstab 1:5 auf dem DLR-Rollprüfstand durchgeführt wurden, vorgestellt

Virtuelle Bahnsysteme

Zukunftsweisendes Ziel virtueller Technologien ist die vollständige Konzeption eines Produkts im Rechner (virtuelles Produkt) mit anschließender automatischer Fertigung und Produktbegleitung bis hin zu späteren Entsorgung mit Recycling. Wichtige Teilziele sind beispielsweise, Entwicklungszeiten erheblich zu verkürzen sowie Entwicklungskosten deutlich zu senken. Eine zentrale Frage ist bei allen aktuellen Fahrzeugentwicklungen die Notwendigkeit zur Gewichtsreduktion, insbesondere der Ersatz schwerer, verschleißanfälliger Mechanik durch volle Integration der Elektronik

Modellierung geregelter Antriebe in der Mehrkoerpersimulation

Oberpfaffenhofen 970814

Immunological characterization of abnormal prion protein from atypical scrapie cases in sheep using a panel of monoclonal antibodies

After the implementation of an active surveillance programme for scrapie in sheep in the EU, the number of diagnosed classical scrapie cases rose sharply and a novel kind of so-called atypical scrapie case was discovered. These atypical scrapie cases display unusual features concerning the distribution of the abnormal prion protein (PrPSc) in the brain, a distinct electrophoretic profile of PrPSc and an inconsistent reaction pattern in the currently used rapid tests. In this report, PrPSc of two German atypical sheep scrapie cases was characterized by epitope mapping using a panel of 18 monoclonal antibodies that were directed against epitopes located throughout the prion protein. This analysis suggests that PrPSc derived from atypical scrapie cases and treated with proteinase K is largely composed of an 11 kDa fragment (previously referred to as the 12 kDa band) and of polymeric fragments thereof. The 11 kDa band corresponds to a prion protein fragment spanning approximately aa 90¿153 and may therefore represent a novel PrPSc typ

European Activities and Standardisation Efforts in Mechatronics

This paper presents an overview of several European projects whose common activity is the development of simulation tools and design methodologies for mechanic systems in automotive and railway industry. It also covers some standardisation efforts taken place in these projects to provide with common languages, data formats and environments to develop mechatronic systems