Engineered T cell receptors and their potential in molecular medicine

T cell receptors are among the most specific biological structures found in nature and are therefore excellent candidates for the molecular targeting of antigen. It is becoming increasingly apparent that common sets of T cell receptors are frequently used in humans to combat pathogen and cancer derived threats. Given that many of these conserved T cell receptors have high affinity for their target ligands, there is potential to amass virtual banks of “off-the-shelf” receptors for use in a wide range of immunotherapeutic strategies. Additionally, such T cell receptors could become basic blueprints for artificial enhancement through mutagenesis, thereby creating an even better 3-dimensional fit for their cognate targets. Indeed, preliminary approaches using both “natural” and “supernatural” T cell receptors have shown promise in treating autoimmunity and malignancy. This review will discuss these studies and other approaches through which T cell receptors can be exploited in immunodiagnostics, pathogen control and gene therapy.

Trans-cis Isomerism and acylimine formation in DsRed chromophore models: Intrinsic rotation barriers

The chromophore of the red fluorescent protein DsRed contains an acylimine substituent to a GFP-like chromophore structure. The acylimine is formed from the trans peptide linkage between residues F65 and Q66 in immature DsRed, but has a cis configuration in the mature protein. The relationship between acylimine formation and trans–cis isomerization is unresolved. We have calculated bond rotation profiles for models of mature and immature DsRed chromophores using B3LYP DFT. The isomerization barrier is substantially reduced in acylimine-substituted models, providing prima facie evidence that acylimine formation precedes trans–cis isomerization in DsRed chromophores.

Using Rasch modeling to re-evaluate three scales related to physical activity: Enjoyment, perceived benefits and perceived barriers

Studies suggest that enjoyment, perceived benefits and perceived barriers may be important mediators of physical activity. However, the psychometric properties of these scales have not been assessed using Rasch modeling. The purpose of this study was to use Rasch modeling to evaluate the properties of three scales commonly used in physical activity studies: the Physical Activity Enjoyment Scale, the Benefits of Physical Activity Scale and the Barriers to Physical Activity Scale. The scales were administered to 378 healthy adults, aged 25–75 years (50% women, 62% Whites), at the baseline assessment for a lifestyle physical activity intervention trial. The ConQuest software was used to assess model fit, item difficulty, item functioning and standard error of measurement. For all scales, the partial credit model fit the data. Item content of one scale did not adequately cover all respondents. Response options of each scale were not targeting respondents appropriately, and standard error of measurement varied across the total score continuum of each scale. These findings indicate that each scale's effectiveness at detecting differences among individuals may be limited unless changes in scale content and response format are made.

Consumer-identified barriers and strategies for optimizing technology use in the workplace

Purpose. This article explores the experiences of 26 assistive technology (AT) users having a range of physical impairments as they optimized their use of technology in the workplace. Method. A qualitative research design was employed using in-depth, open-ended interviews and observations of AT users in the workplace. Results. Participants identified many factors that limited their use of technology such as discomfort and pain, limited knowledge of the technology's features, and the complexity of the technology. The amount of time required for training, limited work time available for mastery, cost of training and limitations of the training provided, resulted in an over-reliance on trial and error and informal support networks and a sense of isolation. AT users enhanced their use of technology by addressing the ergonomics of the workstation and customizing the technology to address individual needs and strategies. Other key strategies included tailored training and learning support as well as opportunities to practice using the technology and explore its features away from work demands. Conclusions. This research identified structures important for effective AT use in the workplace which need to be put in place to ensure that AT users are able to master and optimize their use of technology.

Tempus: Barriers, Borders, Boundaries: Proceedings of the 2001 Australian Archaeological Association Annual Conference

The conference aimed to provide a forum for the exploration of barriers, borders and boundaries in Australian archaeological methods and practice, frameworks of interpretation and epistemological structures. Sessions were designed to have broad appeal to a range of archaeological stakeholders including academics, consultants, Indigenous peoples, students, cultural heritage managers and policy formulators.