Electromechanical systems with transient high power response operating from a resonant AC link

The combination of an inherently robust asynchronous (induction) electrical machine with the rapid control of energy provided by a high frequency resonant AC link enables the efficient management of higher power levels with greater versatility. This could have a variety of applications from launch vehicles to all-electric automobiles. These types of systems utilize a machine which is operated by independent control of both the voltage and frequency. This is made possible by using an indirect field-oriented control method which allows instantaneous torque control in all four operating quadrants. Incorporating the AC link allows the converter in these systems to switch at the zero crossing of every half cycle of the AC waveform. This zero loss switching of the link allows rapid energy variations to be achieved without the usual frequency proportional switching loss. Several field-oriented control systems were developed by LeRC and General Dynamics Space Systems Division under contract to NASA. A description of a single motor, electromechanical actuation system is presented. Then, focus is on a conceptual design for an AC electric vehicle. This design incorporates an induction motor/generator together with a flywheel for peak energy storage. System operation and implications along with the associated circuitry are addressed. Such a system would greatly improve all-electric vehicle ranges over the Federal Urban Driving Cycle (FUD)

Field oriented control of induction motors

Induction motors have always been known for their simple rugged construction, but until lately were not suitable for variable speed or servo drives due to the inherent complexity of the controls. With the advent of field oriented control (FOC), however, the induction motor has become an attractive option for these types of drive systems. An FOC system which utilizes the pulse population modulation method to synthesize the motor drive frequencies is examined. This system allows for a variable voltage to frequency ratio and enables the user to have independent control of both the speed and torque of an induction motor. A second generation of the control boards were developed and tested with the next point of focus being the minimization of the size and complexity of these controls. Many options were considered with the best approach being the use of a digital signal processor (DSP) due to its inherent ability to quickly evaluate control algorithms. The present test results of the system and the status of the optimization process using a DSP are discussed

'This isn't what mine looked like': a qualitative study of symptom appraisal and help seeking in people recently diagnosed with melanoma.

OBJECTIVE: To explore symptom appraisal and help-seeking decisions among patients recently diagnosed with melanomas, and to compare experiences of people with 'thinner' (2 mm) melanomas, as thickness at diagnosis is an important prognostic feature. METHODS: In-depth interviews with patients within 10 weeks of melanoma diagnosis explored the factors impacting on their pathways to diagnosis. Framework analysis, underpinned by the Model of Pathways to Treatment, was used to explore the data with particular focus on patients' beliefs and experiences, disease factors, and healthcare professional (HCP) influences. RESULTS: 63 patients were interviewed (29-93 years, 31 women, 30 thicker melanomas). All described their skin changes using rich lay vocabulary. Many included unassuming features such as 'just a little spot' as well as common features of changes in size, colour and shape. There appeared to be subtly different patterns of symptoms: descriptions of vertical growth, bleeding, oozing and itch were features of thicker melanomas irrespective of pathological type. Appraisal was influenced by explanations such as normal life changes, prior beliefs and whether skin changes matched known melanoma descriptions. Most decisions to seek help were triggered by common factors such as advice from family and friends. 11 patients reported previous reassurance about their skin changes by a HCP, with little guidance on monitoring change or when it would be appropriate to re-consult. CONCLUSIONS: Patients diagnosed with both thinner and thicker melanomas often did not initially recognise or interpret their skin changes as warning signs or prompts to seek timely medical attention. The findings provide guidance for melanoma awareness campaigns on more appropriate images, helpful descriptive language and the need to stress the often apparently innocuous nature of potentially serious skin changes. The importance of appropriate advice, monitoring and safety-netting procedures by HCPs for people presenting with skin changes is also highlighted.Thanks to our funding organisation the National Awareness and Early Diagnosis Initiative (NAEDI), and to their funding partners: Cancer Research UK; Department of Health, England; Economic and Social Research Council; Health and Social Care Research and Development Division; Public Health Agency, Northern Ireland, National Institute for Social Care and Health Research, Wales and the Scottish Government. All researchers were independent of the funding body and the study sponsors and funder had no role in study design; data collection, analysis and interpretation of data; in the writing of the report; or decision to submit the article for publication. FW was supported by an NIHR Clinical Lectureship followed by a NIHR Clinician Scientist award at the time of this study. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.This is the final published version. It's also available from BMJ Open at http://bmjopen.bmj.com/content/4/7/e005566.abstract

CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold

The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity

CD8+ T-­cell specificity is compromised at a defined major histocompatibility complex class I/CD8 affinity threshold

The CD8 co-receptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR)-binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~10-fold). In this study, we used a panel of MHCI mutants with altered CD8-binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity

Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors

Evidence indicates that autoimmunity can be triggered by virus-specific CD8+ T cells that crossreact with self-derived peptide epitopes presented on the cell surface by major histocompatibility complex class I (MHCI) molecules. Identification of the associated viral pathogens is challenging because individual T-cell receptors can potentially recognize up to a million different peptides. Here, we generate peptide length-matched combinatorial peptide library (CPL) scan data for a panel of virus-specific CD8+ T-cell clones spanning different restriction elements and a range of epitope lengths. CPL scan data drove a protein database search limited to viruses that infect humans. Peptide sequences were ranked in order of likelihood of recognition. For all anti-viral CD8+ T-cell clones examined in this study, the index peptide was either the top-ranked sequence or ranked as one of the most likely sequences to be recognized. Thus, we demonstrate that anti-viral CD8+ T-cell clones are highly focused on their index peptide sequence and that ‘CPL-driven database searching’ can be used to identify the inciting virus-derived epitope for a given CD8+ T-cell clone. Moreover, to augment access to CPL-driven database searching, we have created a publicly accessible webtool. Application of these methodologies in the clinical setting may clarify the role of viral pathogens in the etiology of autoimmune diseases

CD8+ T-cell specificity is compromised at a defined MHCI/CD8 affinity threshold

The CD8 coreceptor engages peptide-major histocompatibility complex class I (pMHCI) molecules at a largely invariant site distinct from the T-cell receptor (TCR) binding platform and enhances the sensitivity of antigen-driven activation to promote effective CD8+ T-cell immunity. A small increase in the strength of the pMHCI/CD8 interaction (~ 1.5-fold) can disproportionately amplify this effect, boosting antigen sensitivity by up to two orders of magnitude. However, recognition specificity is lost altogether with more substantial increases in pMHCI/CD8 affinity (~ 10-fold). In this study, we used a panel of MHCI mutants with altered CD8 binding properties to show that TCR-mediated antigen specificity is delimited by a pMHCI/CD8 affinity threshold. Our findings suggest that CD8 can be engineered within certain biophysical parameters to enhance the therapeutic efficacy of adoptive T-cell transfer irrespective of antigen specificity. The pMHCI/CD8 interaction controls specificit

Diabetes Interactive Atlas

The Diabetes Interactive Atlas is a recently released Web-based collection of maps that allows users to view geographic patterns and examine trends in diabetes and its risk factors over time across the United States and within states. The atlas provides maps, tables, graphs, and motion charts that depict national, state, and county data. Large amounts of data can be viewed in various ways simultaneously. In this article, we describe the design and technical issues for developing the atlas and provide an overview of the atlas’ maps and graphs. The Diabetes Interactive Atlas improves visualization of geographic patterns, highlights observation of trends, and demonstrates the concomitant geographic and temporal growth of diabetes and obesity