Magnetron Development

Contains reports on two research projects

Magnetron Development

Contains reports on three research projects

Portuguese validation of the Cambridge pulmonary hypertension outcome review (CAMPHOR) questionnaire

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) and other forms of precapillary pulmonary hypertension (PH) have impaired quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a PH-specific patient-reported outcome measure that assesses symptoms, activity limitations and QoL. It was originally developed in UK-English. The main objective of this study was to create an adaptation of the CAMPHOR suitable for a Portuguese-speaking population. METHODS: A multi-step approach was followed: bilingual and lay panel translation; cognitive debriefing interviews; and psychometric testing in repeated postal surveys (2 weeks apart) including assessment of internal consistency, reproducibility and validity. The Nottingham Health Profile (NHP) questionnaire was used as a comparator instrument to test convergent validity. RESULTS: The CAMPHOR was translated without difficulty by the two panels. Cognitive debriefing interviews showed the questionnaire was easily understood and considered relevant to patients' experience with their illness. Psychometric evaluation was performed with 50 PAH patients (47 ± 14 years, 37 women). Cronbach's alpha coefficients showed good internal consistency for the three CAMPHOR scales [Symptoms = 0.95; Activities = 0.93 and QoL = 0.94]. Test-retest coefficients showed that all scales had excellent reliability (Symptoms = 0.94; Activities = 0.89 and QoL = 0.93), indicating low levels of random measurement error. The CAMPHOR correlated as expected with the NHP. The magnitude of correlations followed a similar pattern to those in the original development study. The CAMPHOR also exhibited evidence of known group validity in its ability to distinguish between self-reported severity and general health groups. CONCLUSIONS: A valid and reliable version of the CAMPHOR questionnaire for the European Portuguese-speaking population was developed and is recommended for use.info:eu-repo/semantics/publishedVersio

Seasonal changes in microbial community structure and activity imply winter production is linked to summer hypoxia in a large lake

Carbon and nutrient cycles in large temperate lakes such as Lake Erie are primarily driven by phototrophic and heterotrophic microorganisms, although our understanding of these is often constrained to late spring through summer due to logistical constraints. During periods of \u3e 90% ice cover in February of 2008, 2009, and 2010, we collected samples from an icebreaker for an examination of bacterial production as well as microbial community structure. In comparison with summer months (August 2002 and 2010), we tested hypotheses concerning seasonal changes in microbial community diversity and production. Bacterial production estimates were c. 2 orders of magnitude higher (volume normalized) in summer relative to winter. Our observations further demonstrate that the microbial community, including single-celled phototrophs, varied in composition between August and February. Sediment traps deployed and collected over a 3 year period (2008-2011) confirmed that carbon export was ongoing and not limiting winter production. The results support the notion that active primary producers in winter months export carbon to the sediments that is not consumed until the warmer seasons. The establishment of this linkage is a critical observation in efforts to understand the extent and severity of annual summertime formations of a zone of regional hypoxia in Lake Erie. Seasonal changes in microbial community productivity and diversity suggest primary production in winter months may exacerbate summer hypoxia in Lake Eri. © 2014 Federation of European Microbiological Societies

Methods for detecting flaring structures in Sagittarius A* with high frequency VLBI

The super massive black hole candidate, Sagittarius A*, exhibits variability from radio to X-ray wavelengths on time scales that correspond to < 10 Schwarzschild radii. We survey the potential of millimeter-wavelength VLBI to detect and constrain time variable structures that could give rise to such variations, focusing on a model in which an orbiting hot spot is embedded in an accretion disk. Non-imaging algorithms are developed that use interferometric closure quantities to test for periodicity, and applied to an ensemble of hot-spot models that sample a range of parameter space. We find that structural periodicity in a wide range of cases can be detected on most potential VLBI arrays using modern VLBI instrumentation. Future enhancements of mm/sub-mm VLBI arrays including phased array processors to aggregate VLBI station collecting area, increased bandwidth recording, and addition of new VLBI sites all significantly aid periodicity detection. The methods described herein can be applied to other models of Sagittarius A*, including jet outflows and Magneto-Hydrodynamic accretion simulations.Comment: Submitted to Ap

Extracellular Stimuli Specifically Regulate Localized Levels of Individual Neuronal mRNAs

Subcellular regulation of protein synthesis requires the correct localization of messenger RNAs (mRNAs) within the cell. In this study, we investigate whether the axonal localization of neuronal mRNAs is regulated by extracellular stimuli. By profiling axonal levels of 50 mRNAs detected in regenerating adult sensory axons, we show that neurotrophins can increase and decrease levels of axonal mRNAs. Neurotrophins (nerve growth factor, brainderived neurotrophic factor, and neurotrophin-3) regulate axonal mRNA levels and use distinct downstream signals to localize individual mRNAs. However, myelin-associated glycoprotein and semaphorin 3A regulate axonal levels of different mRNAs and elicit the opposite effect on axonal mRNA levels from those observed with neurotrophins. The axonal mRNAs accumulate at or are depleted from points of ligand stimulation along the axons. The translation product of a chimeric green fluorescent protein–β-actin mRNA showed similar accumulation or depletion adjacent to stimuli that increase or decrease axonal levels of endogenous β-actin mRNA. Thus, extracellular ligands can regulate protein generation within subcellular regions by specifically altering the localized levels of particular mRNAs

Evaluation of Germline BMP4 Mutation as a Cause of Colorectal Cancer

Transforming growth factor-â (TGF-â) signalling plays a key role in colorectal cancer (CRC). Bone morphogenetic protein-4 (BMP4) is a member of the TGF-â family of signal transduction molecules. To examine if germline mutation in BMP4 causes CRC we analysed 504 genetically enriched CRC cases (by virtue of early-onset disease, family history of CRC) for mutations in the coding sequence of BMP4. We identified three pathogenic mutations, p.R286X (g.8330C>T), p.W325C (g.8449G>T) and p.C373S (g.8592G>C), amongst the CRC cases which were not observed in 524 healthy controls. p.R286X localizes to the N-terminal of the TGF-â1 prodomain truncating the protein prior to the active domain. p.W325C and p.C373S mutations are predicted from protein homology modelling with BMP2 to impact deleteriously on BMP4 function. Segregation of p.C373S with adenoma and hyperplastic polyp in first-degree relatives of the case suggests germline mutations may confer a juvenile polyposis-type phenotype. These findings suggest mutation of BMP4is a cause of CRC and the value of protein-based modelling in the elucidation of rare disease-causing variants. © 2010 Wiley-Liss, Inc