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Summary: Understanding the mechanisms for cellular aging is a fundamental question in biology. Normal red blood cells (RBCs) survive for approximately 100 days, and their survival is likely limited by functional decline secondary to cumulative damage to cell constituents, which may be reflected in altered metabolic capabilities. To investigate metabolic changes during in vivo RBC aging, labeled cell populations were purified at intervals and assessed for abundance of metabolic intermediates using mass spectrometry. A total of 167 metabolites were profiled and quantified from cell populations of defined ages. Older RBCs maintained ATP and redox charge states at the cost of altered activity of enzymatic pathways. Time-dependent changes were identified in metabolites related to maintenance of the redox state and membrane structure. These findings illuminate the differential metabolic pathway usage associated with normal cellular aging and identify potential biomarkers to determine average RBC age and rates of RBC turnover from a single blood sample.

Delphi consensus consultation methods and community-based participatory research (CBPR) are distinct approaches that have traditionally been employed separately. This paper explores the integration of Delphi methods with CBPR in a research project that sought to identify effective self-management strategies for bipolar disorder (BD). We introduce our Canadian-based network which specializes in CBPR in BD, and outline the key principles of CBPR approaches. Delphi consensus consultation methods are described and we present the five phases of our Delphi consensus consultation project, conducted within a CBPR framework. Examples of how each project phase incorporated the principles of CBPR are provided, as are personal reflections of community members involved in the project, and broader reflections on challenges commonly encountered in CBPR projects.

Starting with a description of the software and hardware used for corpus linguistics in the late 1980s to early 1990s, this contribution discusses difficulties faced by the software designer when attempting to allow users to study text. Future human-machine interfaces may develop to be much more sophisticated, and certainly the aspects of text which can be studied will progress beyond plain text without images. Another area which will develop further is the study of patternings involving not just single words but word-relations across large stretches of text.

WordSmith Tools, since its launch in 1996, has had a rather unusual history and the aim of this paper is to record some of the chief influences on its development. The paper thus presents and discusses the history of WordSmith Tools and its predecessors going back to the early 1980s when processors were much slower, memory very limited and disk space expensive. It is structured around the discussion of certain key issues, principles and themes. These include: “on the fly” processing, corpus flexibility, language independence, user control aspects, the unpredictability of design needs, a move towards remote processes, modular construction principles, software production management, pattern-seeking and the development of new corpus linguistic terms.

PrP(Sc), a misfolded and aggregated form of the cellular prion protein PrP(C), is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrP(C) in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrP(C) and PrP(Sc). Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrP(C). Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrP(C). Some of these antibodies recognize epitopes that are resilient to protease digestion in PrP(Sc). Other antibodies immunoprecipitate PrP(C), but not PrP(Sc). A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrP(C) and PrP(Sc). Amino-proximal antibodies were found to react with repetitive PrP(C) epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays.

ABSTRACT This paper presents the Download Parser, a tool for handling text downloads from large online databases. Many universities have access to full-text databases which allow the user to search their holdings and then view and ideally download the full text of relevant articles, but there are important problems in practice in managing such downloads, because of factors such as duplication, unevenness of formatting standards, lack of documentation. The tool under discussion was devised to parse downloads, clean them up and standardise them, identify headlines and insert suitably marked-up headers for corpus analysis.