Intra- and interspecies interactions between prion proteins and effects of mutations and polymorphisms

Recently, crystallization of the prion protein in a dimeric form was reported. Here we show that native soluble homogenous FLAG-tagged prion proteins from hamster, man and cattle expressed in the baculovirus system are predominantly dimeric. The PrP/PrP interaction was confirmed in Semliki Forest virus-RNA transfected BHK cells co-expressing FLAG- and oligohistidine-tagged human PrP. The yeast two-hybrid system identified the octarepeat region and the C-terminal structured domain (aa90-aa230) of PrP as PrP/PrP interaction domains. Additional octarepeats identified in patients suffering from fCJD reduced (wtPrP versus PrP+90R) and completely abolished (PrP+90R versus PrP+90R) the PrP/PrP interaction in the yeast two-hybrid system. In contrast, the Met/Val polymorphism (aa129), the GSS mutation Pro102Leu and the FFI mutation Asp178Asn did not affect PrP/PrP interactions. Proof of interactions between human or sheep and bovine PrP, and sheep and human PrP, as well as lack of interactions between human or bovine PrP and hamster PrP suggest that interspecies PrP interaction studies in the yeast two-hybrid system may serve as a rapid pre-assay to investigate species barriers in prion diseases

A prototype ASIC for APD array readout of scintillating plastic fibers

We report on the development of custom front-end electronics for use with avalanche photodiode (APD) arrays as part of a NASA technology study for the readout of scintillating plastic fibers. APD arrays featuring 64 1 mm square pixels are used. We demonstrate that a pixel of these APD arrays coupled to relatively thin (0.25 mm) and short (15 cm) scintillating plastic fibers can be used to detect and measure the tracks of even minimum ionizing particles (MIPs). An applicationspecific integrated circuit (ASIC) implementation of the electronics is required to produce a detector sufficiently compact for practical use in a flight experiment featuring many thousands of channels. This paper briefly describes the detector concept and performance and presents the design and performance of a four-channel prototype ASIC fabricated using the 0.35 micron TSMC process

Time Marches on, and So Does the History of Public Relations

Editor's Introduction to History of Public Relations special issu

Evaluation of long-term clinical and health service outcomes following coronary artery revascularisation in Western Australia (WACARP): a population-based cohort study protocol

Introduction: Coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) are procedures commonly performed on patients with significant obstructive coronary artery disease to relieve symptoms of ischaemia, improve survival or both. Although the efficacy of both procedures at the individual level has been established, the impact of advances in coronary artery revascularisation procedures (CARP) on long-term outcomes and cost-effectiveness at the population level are yet to be assessed. Our aim is to evaluate a minimum of 6-year outcomes and costs for the total population of patients who had CARP in Western Australia (WA) in 2000–2005. Methods and analysis This retrospective population cohort study will link clinical and administrative health data for a previously defined cohort including all patients in WA who had a CARP in the period 2000–2005. The cohort consists of 19 014 patients who had 21 175 procedures (15 429 PCI and 5746 CABG). We are now collecting a minimum of 6 years follow-up of morbidity and mortality data for the cohort using the WA Data Linkage System, clinical registries and hospital records, with 12 years follow-up for cases in the year 2000. Comparison of long-term outcomes for different CARP will be reported (PCI vs CABG; bare metal stents vs drug-eluting stents vs CABG). Cost-effectiveness analysis of CARP from the perspective of the healthcare sector will be performed using individual level cost data and average costs from Australian Refined Diagnosis Related Groups. Ethics and dissemination This study has received ethics approval from the University of Western Australia, the Western Australian Department of Health and all participating hospitals. Being a large population cohort study, approval included a waiver of informed consent. All findings will be presented at local, national and international healthcare/academic conferences and published in peer-reviewed journals

Defining the gap between research and practice in public relations programme evaluation - towards a new research agenda

The current situation in public relations programme evaluation is neatly summarized by McCoy who commented that 'probably the most common buzzwords in public relations in the last ten years have been evaluation and accountability' (McCoy 2005, 3). This paper examines the academic and practitioner-based literature and research on programme evaluation and it detects different priorities and approaches that may partly explain why the debate on acceptable and agreed evaluation methods continues. It analyses those differences and proposes a research agenda to bridge the gap and move the debate forward

The VOrtex Ring Transit EXperiment (VORTEX) GAS project

Get Away Special (GAS) payload G-093, also called VORTEX (VOrtex Ring Transit EXperiment), is an investigation of the propagation of a vortex ring through a liquid-gas interface in microgravity. This process results in the formation of one or more liquid droplets similar to earth based liquid atomization systems. In the absence of gravity, surface tension effects dominate the drop formation process. The Shuttle's microgravity environment allows the study of the same fluid atomization processes as using a larger drop size than is possible on Earth. This enables detailed experimental studies of the complex flow processes encountered in liquid atomization systems. With VORTEX, deformations in both the vortex ring and the fluid surface will be measured closely for the first time in a parameters range that accurately resembles liquid atomization. The experimental apparatus will record images of the interactions for analysis after the payload has been returned to earth. The current design of the VORTEX payload consists of a fluid test cell with a vortex ring generator, digital imaging system, laser illumination system, computer based controller, batteries for payload power, and an array of housekeeping and payload monitoring sensors. It is a self-contained experiment and will be flown on board the Space Shuttle in a 5 cubic feet GAS canister. The VORTEX Project is entirely run by students at the University of Michigan but is overseen by a faculty advisor acting as the payload customer and the contact person with NASA. This paper summarizes both the technical and programmatic aspects of the VORTEX Project

Experimental transmission of chronic wasting disease agent from mule deer to cattle by the intracerebral route

This communication reports final observations on experimental transmission of chronic wasting disease (CWD) from mule deer to cattle by the intracerebral route. Thirteen calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. Three other calves were kept as uninoculated controls. The experiment was terminated 6 years after inoculation. During that time, abnormal prion protein (PrPres) was demonstrated in the central nervous system (CNS) of 5 cattle by both immunohistochemistry and Western blot. However, microscopic lesions suggestive of spongiform encephalopathy (SE) in the brains of these PrPres-positive animals were subtle in 3 cases and absent in 2 cases. Analysis of the gene encoding bovine PRNP revealed homozygosity for alleles encoding 6 octapeptide repeats, serine (S) at codon 46, and S at codon 146 in all samples. Findings of this study show that although PrPres amplification occurred after direct inoculation into the brain, none of the affected animals had classic histopathologic lesions of SE. Furthermore, only 38% of the inoculated cattle demonstrated amplification of PrPres. Although intracerebral inoculation is an unnatural route of exposure, this experiment shows that CWD transmission in cattle could have long incubation periods (up to 5 years). This finding suggests that oral exposure of cattle to CWD agent, a more natural potential route of exposure, would require not only a much larger dose of inoculum but also may not result in amplification of PrPres within CNS tissues during the normal lifespan of cattle

Experimental transmission of chronic wasting disease agent from mule deer to cattle by the intracerebral route

This communication reports final observations on experimental transmission of chronic wasting disease (CWD) from mule deer to cattle by the intracerebral route. Thirteen calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. Three other calves were kept as uninoculated controls. The experiment was terminated 6 years after inoculation. During that time, abnormal prion protein (PrPres) was demonstrated in the central nervous system (CNS) of 5 cattle by both immunohistochemistry and Western blot. However, microscopic lesions suggestive of spongiform encephalopathy (SE) in the brains of these PrPres-positive animals were subtle in 3 cases and absent in 2 cases. Analysis of the gene encoding bovine PRNP revealed homozygosity for alleles encoding 6 octapeptide repeats, serine (S) at codon 46, and S at codon 146 in all samples. Findings of this study show that although PrPres amplification occurred after direct inoculation into the brain, none of the affected animals had classic histopathologic lesions of SE. Furthermore, only 38% of the inoculated cattle demonstrated amplification of PrPres. Although intracerebral inoculation is an unnatural route of exposure, this experiment shows that CWD transmission in cattle could have long incubation periods (up to 5 years). This finding suggests that oral exposure of cattle to CWD agent, a more natural potential route of exposure, would require not only a much larger dose of inoculum but also may not result in amplification of PrPres within CNS tissues during the normal lifespan of cattle

Early glycoprotein IIb–IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis

Background: Even though time-to-treatment has been shown to be a determinant of mortality in primary angioplasty, the potential benefits from early pharmacological reperfusion by glycoprotein (Gp) IIb-IIIa inhibitors are still unclear. The aim of this meta-analysis was to combine individual data from all randomised trials conducted on facilitated primary angioplasty by the use of early Gp IIb-IIIa inhibitors. Methods and results: The literature was scanned by formal searches of electronic databases (MEDLINE, EMBASE) from January 1990 to October 2007. All randomised trials on facilitation by the early administration of Gp IIb-IIIa inhibitors in ST-segment elevation myocardial infarction (STEMI) were examined. No language restrictions were enforced. Individual patient data were obtained from 11 out of 13 trials, including 1662 patients (840 patients (50.5%) randomly assigned to early and 822 patients (49.5%) to late Gp IIb-IIIa inhibitor administration). Preprocedural Thrombolysis in Myocardial Infarction Study (TIMI) grade 3 flow was more frequent with early Gp IIb-IIIa inhibitors. Postprocedural TIMI 3 flow and myocardial blush grade 3 were higher with early Gp IIb IIIa inhibitors but did not reach statistical significance except for abciximab, whereas the rate of complete ST-segment resolution was significantly higher with early Gp IIb-IIIa inhibitors. Mortality was not significantly different between groups, although early abciximab demonstrated improved survival compared with late administration, even after adjustment for clinical and angiographic confounding factors. Conclusions: This meta-analysis shows that pharmacological facilitation with the early administration of Gp IIb IIIa inhibitors in patients undergoing primary angioplasty for STEMI is associated with significant benefits in terms of preprocedural epicardial recanalisation and ST-segment resolution, which translated into non-significant mortality benefits except for abciximab