A review of calcineurin biophysics with implications for cardiac physiology

Calmodulin is a prevalent calcium sensing protein found in all cells. Three genes exist for calmodulin and all three of these genes encode for the exact same protein sequence. Recently mutations in the amino acid sequence of calmodulin have been identified in living human patients. Thus far, patients harboring these mutations in the calmodulin sequence have only displayed an altered cardiac related phenotype. Calcineurin is involved in many key physiological processes and its activity is regulated by calcium and calmodulin. In order to assess whether or not calcineurin contributes to calmodulinopathy (a pathological state arising from dysfunctional calmodulin), a comprehensive search of relevant literature has been performed. Herein, the physiological roles of calcineurin and consequences of dysfunction have been reviewed for literature focused on the heart

Varying potential silicon carbide gas sensor

A hydrocarbon gas detection device operates by dissociating or electro-chemically oxidizing hydrocarbons adsorbed to a silicon carbide detection layer. Dissociation or oxidation are driven by a varying potential applied to the detection layer. Different hydrocarbon species undergo reaction at different applied potentials so that the device is able to discriminate among various hydrocarbon species. The device can operate at temperatures between 100.degree. C. and at least 650.degree. C., allowing hydrocarbon detection in hot exhaust gases. The dissociation reaction is detected either as a change in a capacitor or, preferably, as a change of current flow through an FET which incorporates the silicon carbide detection layers. The silicon carbide detection layer can be augmented with a pad of catalytic material which provides a signal without an applied potential. Comparisons between the catalytically produced signal and the varying potential produced signal may further help identify the hydrocarbon present

Climatic versus biotic constraints on carbon and water fluxes in seasonally drought-affected ponderosa pine ecosystems

We investigated the relative importance of climatic versus biotic controls on gross primary production (GPP) and water vapor fluxes in seasonally drought-affected ponderosa pine forests. The study was conducted in young (YS), mature (MS), and old stands (OS) over 4 years at the AmeriFlux Metolius sites. Model simulations showed that interannual variation of GPP did not follow the same trends as precipitation, and effects of climatic variation were smallest at the OS (50%), and intermediate at the YS (<20%). In the young, developing stand, interannual variation in leaf area has larger effects on fluxes than climate, although leaf area is a function of climate in that climate can interact with age-related shifts in carbon allocation and affect whole-tree hydraulic conductance. Older forests, with well-established root systems, appear to be better buffered from effects of seasonal drought and interannual climatic variation. Interannual variation of net ecosystem exchange (NEE) was also lowest at the OS, where NEE is controlled more by interannual variation of ecosystem respiration, 70% of which is from soil, than by the variation of GPP, whereas variation in GPP is the primary reason for interannual changes in NEE at the YS and MS. Across spatially heterogeneous landscapes with high frequency of younger stands resulting from natural and anthropogenic disturbances, interannual climatic variation and change in leaf area are likely to result in large interannual variation in GPP and NEE

An Experimental Investigation of Conformational Fluctuations in Proteins G and L

SummaryThe B1 domains of streptococcal proteins G and L are structurally similar, but they have different sequences and they fold differently. We have measured their NMR spectra at variable temperature using a range of concentrations of denaturant. Many residues have curved amide proton temperature dependence, indicating that they significantly populate alternative, locally unfolded conformations. The results, therefore, provide a view of the locations of low-lying, locally unfolded conformations. They indicate approximately 4–6 local minima for each protein, all within ca. 2.5 kcal/mol of the native state, implying a locally rough energy landscape. Comparison with folding data for these proteins shows that folding involves most molecules traversing a similar path, once a transition state containing a β hairpin has been formed, thereby defining a well-populated pathway down the folding funnel. The hairpin that directs the folding pathway differs for the two proteins and remains the most stable part of the folded protein

A National Survey of Water-Based Leisure Activities in Ireland 2003

This survey profiles the domestic market for water-based tourism, sport and leisure in Ireland. The data provides up-to-date statistical information on 18 water-based leisure activities broadly grouped under the following categories: Seaside/Resort trips; Angling; Coastal and Inland Boating; and Watersports. The objective of the survey is to demonstrate the significant contribution of marine leisure activity to the national economy, and to highlight emerging trends and the potential for development of our water-based leisure resources. A key finding of the survey, conducted by the ESRI in 2003, is that marine leisure activity based on Ireland’s marine and freshwater resources generates €434 million in expenditure by Irish residents, and approximately 5,100 jobs are supported by this level of expenditure. A comparison of the domestic tourism market and the water-based tourism domestic market further highlights the value of the sector. In 2003, water-based tourism accounted for 22 per cent of the domestic tourism market and generated 45 per cent of domestic tourism revenue. Our seaside resorts, beaches, inland waterways and rivers provide the resource for a wide range of water-based tourism recreation, sport and leisure activities. The survey results show that 1.48 million persons, representing 49 per cent of the adult population participated in some form of water-based activity during the survey period. Although overall satisfaction with facilities was high, a further 10 per cent of the adult population (294,100) said they would take up some marine leisure activity if facilities were better. This demonstrates the potential and scope for development in the sector

Mirror on the Field: Gender, Authorship, and Research Methods in Higher Education’s Leading Journals

Framed conceptually by gender equity, gender homophily, the contest regime of blind peer-review publishing, and the gendered nature of the quantitative–qualitative debate, this study investigated the intersection of authorship, gender, and methodological characteristics of 408 articles published from 2006 to 2010 in 3 major higher education journals. Nonbinary coding of author gender based on pronouns identified via Web searches virtually eliminated missing data and likely reduced error. Results suggest movement toward gender parity over time; however, women’s representation among authors does not appear commensurate with representation in the field. Findings revealed gendered use of research methods, with qualitative articles more likely to be first-authored by women and quantitative articles more likely to be first-authored by men. Nevertheless, articles first-authored by both women and men were more likely to use quantitative than qualitative methods. Quantitative research, more so than qualitative research, appears to be a site of cogender collaboration, which has increased over time. This portrait of the intersection of authorship, gender, and research methods provides an empirical foundation for discussion and inquiry about gender and scholarship in the field, and the results of our study are generative for future research

In the beginning: Role of autonomy support on the motivation, mental health and intentions of participants entering an exercise referral scheme

Self-determination theory (Deci & Ryan, 2000, Intrinsic motivation and self-determination in human behaviour. New York: Plenum Publishing) highlights the impact autonomy supportive environments can have on exercise motivation and positive health outcomes. Yet little is known about whether differential effects occur as a function of which significant other is providing this support. Further, no research has examined the relationship between motivation and the social environment with participants’ mental health and intentions to be physically active before entering an exercise intervention. Study participants were 347 British adults who were about to start an exercise referral scheme. Regression analyses revealed that the effects of autonomy support on mental health and physical activity intentions differed as a function of who provided the support (offspring, partner or physician), with the offspring having the weakest effects. A structural model was supported, indicating that autonomy support and more autonomous regulations led to more positive mental health outcomes and stronger intentions to be physically active. Knowledge of the social environmental and personal motivation of those about to commence an exercise programme can provide important insights for professionals supporting such efforts

X- and gamma-ray observations of the 15 November 1991 Solar Flare

This work expands the current understanding of the 15 November 1991 Solar Flare. The flare was a well observed event in radio to gamma-rays and is the first flare to be extensively studied with the benefit of detailed soft and hard X-ray images. In this work, we add data from all four instruments on the Compton Gamma Ray Observatory. Using these data we determined that the accelerated electron spectrum above 170 keV is best fit with a power law with a spectral index of −4.6, while the accelerated proton spectrum above 0.6 MeV is fit with a power law of spectral index −4.5. From this we computed lower limits for the energy content of these particles of∼1023 ergs (electrons) and ∼1027 ergs (ions above 0.6 MeV). These particles do not have enough energy to produce the white-light emission observed from this event. We computed a time constant of 26+20−15 s for the 2.223 MeV neutron capture line, which is consistent at the 2σ level with the lowest values of ∼70 s found for other flares. The mechanism for this short capture time may be better understood after analyses of high energy EGRET data that show potential evidence for pion emission near ∼100 MeV

90-Day all-cause mortality can be predicted following a total knee replacement:an international, network study to develop and validate a prediction model

Purpose: The purpose of this study was to develop and validate a prediction model for 90-day mortality following a total knee replacement (TKR). TKR is a safe and cost-effective surgical procedure for treating severe knee osteoarthritis (OA). Although complications following surgery are rare, prediction tools could help identify high-risk patients who could be targeted with preventative interventions. The aim was to develop and validate a simple model to help inform treatment choices. Methods: A mortality prediction model for knee OA patients following TKR was developed and externally validated using a US claims database and a UK general practice database. The target population consisted of patients undergoing a primary TKR for knee OA, aged ≥ 40 years and registered for ≥ 1 year before surgery. LASSO logistic regression models were developed for post-operative (90-day) mortality. A second mortality model was developed with a reduced feature set to increase interpretability and usability. Results: A total of 193,615 patients were included, with 40,950 in The Health Improvement Network (THIN) database and 152,665 in Optum. The full model predicting 90-day mortality yielded AUROC of 0.78 when trained in OPTUM and 0.70 when externally validated on THIN. The 12 variable model achieved internal AUROC of 0.77 and external AUROC of 0.71 in THIN. Conclusions: A simple prediction model based on sex, age, and 10 comorbidities that can identify patients at high risk of short-term mortality following TKR was developed that demonstrated good, robust performance. The 12-feature mortality model is easily implemented and the performance suggests it could be used to inform evidence based shared decision-making prior to surgery and targeting prophylaxis for those at high risk. Level of evidence: III.</p