197 research outputs found

    ENUMERATING LABELLED GRAPHS WITH CERTAIN NEIGHBORHOOD PROPERTIES

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    Properties of (connected) graphs whose closed or open neighborhood families are Sperner, anti-Sperner, distinct or none of the proceeding have been extensively examined. In this paper we examine 24 properties of the neighborhood family of a graph. We give asymptotic formulas for the number of (connected) labelled graphs for 12 of these properties. For the other 12 properties, we give bounds for the number of such graphs. We also determine the status (a.a.s. or a.a.n.) in Gn,1/2 of all 24 of these properties. Our methods are both constructive and probabilistic

    Drug Discovery Opportunities and Challenges at G Protein Coupled Receptors for Long Chain Free Fatty Acids

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    Discovery of G protein coupled receptors for long chain free fatty acids (FFAs), FFA1 (GPR40) and GPR120, has expanded our understanding of these nutrients as signaling molecules. These receptors have emerged as important sensors for FFA levels in the circulation or the gut lumen, based on evidence from in vitro and rodent models, and an increasing number of human studies. Here we consider their promise as therapeutic targets for metabolic disease, including type 2 diabetes and obesity. FFA1 directly mediates acute FFA-induced glucose-stimulated insulin secretion in pancreatic beta-cells, while GPR120 and FFA1 trigger release of incretins from intestinal endocrine cells, and so indirectly enhance insulin secretion and promote satiety. GPR120 signaling in adipocytes and macrophages also results in insulin sensitizing and beneficial anti-inflammatory effects. Drug discovery has focused on agonists to replicate acute benefits of FFA receptor signaling, with promising early results for FFA1 agonists in man. Controversy surrounding chronic effects of FFA1 on beta-cells illustrates that long term benefits of antagonists also need exploring. It has proved challenging to generate highly selective potent ligands for FFA1 or GPR120 subtypes, given that both receptors have hydrophobic orthosteric binding sites, which are not completely defined and have modest ligand affinity. Structure activity relationships are also reliant on functional read outs, in the absence of robust binding assays to provide direct affinity estimates. Nevertheless synthetic ligands have already helped dissect specific contributions of FFA1 and GPR120 signaling from the many possible cellular effects of FFAs. Approaches including use of fluorescent ligand binding assays, and targeting allosteric receptor sites, may improve further pre-clinical ligand development at these receptors, to exploit their unique potential to target multiple facets of diabetes

    Volunteer Recruitment Packets: Tools for Expanding Volunteer Involvement

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    Extension agents must become proficient volunteer recruiters. The 2003 Kentucky Volunteer Administration Academy developed a volunteer recruitment packet as a tool to be used by Extension professionals, staff, and volunteers. The recruitment packet includes major components that introduce Extension to potential volunteers. Thirteen customized volunteer recruitment packets were developed based upon programmatic need and request frequency. Additional packets can be developed based upon the needs of the program and volunteers. Recruitment packets have been distributed and used in a variety of ways that extend recruitment and marketing efforts to volunteers who are engaged and supervised by the agent

    Orchestrating Volunteer Orientation: Introducing the O.B.O.E. Model

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    Volunteers generally come to their new role with varying levels of knowledge about the organization. An effective orientation program introduces the volunteers to the organization as a whole and to their specific job responsibilities. Orientation can be beneficial in assuring that volunteers have accurate information regarding the organization\u27s purpose, programs, policies, and expectations. The volunteer orientation model (O.B.O.E.) can be adapted to fit any Extension program or non-profit volunteer organization. Divided into four main topics, the orientation program is easily presented in a 90-minute session. Orientation topics of the O.B.O.E. model include: an Opening, Background, Organizational safeguards, and Evaluation

    School-based physical activity intervention for older adolescents: rationale and study protocol for the Burn 2 Learn cluster randomised controlled trial

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    Introduction This trial aims to investigate the impact of a school-based physical activity programme, involving high-intensity interval training (HIIT), on the physical, mental and cognitive health of senior school students. Methods and analysis The Burn 2 Learn (B2L) intervention will be evaluated using a two-arm parallel group cluster randomised controlled trial with allocation occurring at the school level (to treatment or wait-list control). Schools will be recruited in two cohorts from New South Wales, Australia. The trial will aim to recruit ∼720 senior school students (aged 16-18 years) from 20 secondary schools (ie, 10 schools per cohort). A range of implementation strategies will be provided to teachers (eg, training, equipment and support) to facilitate the delivery of HIIT sessions during scheduled classes. In phase I and II (3 months each), teachers will facilitate the delivery of at least two HIIT sessions/week during lesson-time. In phase III (6 months), students will be encouraged to complete sessions outside of lesson-time (teachers may continue to facilitate the delivery of B2L sessions during lesson-time). Study outcomes will be assessed at baseline, 6 months (primary end point) and 12 months. Cardiorespiratory fitness (shuttle run test) is the primary outcome. Secondary outcomes include: vigorous physical activity, muscular fitness, cognition and mental health. A subsample of students will (i) provide hair samples to determine their accumulated exposure to stressful events and (ii) undergo multimodal MRI to examine brain structure and function. A process evaluation will be conducted (ie, recruitment, retention, attendance and programme satisfaction)

    A systematic review: Role of dietary supplements on markers of exercise-associated gut damage and permeability

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    Nutrition strategies and supplements may have a role to play in diminishing exercise associated gastrointestinal cell damage and permeability. The aim of this systematic review was to determine the influence of dietary supplements on markers of exercise-induced gut endothelial cell damage and/or permeability. Five databases were searched through to February 2021. Studies were selected that evaluated indirect markers of gut endothelial cell damage and permeability in response to exercise with and without a specified supplement, including with and without water. Acute and chronic supplementation protocols were included. Twenty-seven studies were included. The studies investigated a wide range of supplements including bovine colostrum, glutamine, probiotics, supplemental carbohydrate and protein, nitrate or nitrate precursors and water across a variety of endurance exercise protocols. The majority of studies using bovine colostrum and glutamine demonstrated a reduction in selected markers of gut cell damage and permeability compared to placebo conditions. Carbohydrate intake before and during exercise and maintaining euhydration may partially mitigate gut damage and permeability but coincide with other performance nutrition strategies. Single strain probiotic strains showed some positive findings, but the results are likely strain, dosage and duration specific. Bovine colostrum, glutamine, carbohydrate supplementation and maintaining euhydration may reduce exercise-associated endothelial damage and improve gut permeability. In spite of a large heterogeneity across the selected studies, appropriate inclusion of different nutrition strategies could mitigate the initial phases of gastrointestinal cell disturbances in athletes associated with exercise. However, research is needed to clarify if this will contribute to improved athlete gastrointestinal and performance outcomes

    Temperature

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    KEY HEADLINES: • The first MCCIP ARC in 2006 reported following what was then the warmest year globally in 2005 (0.26°C higher than the 1981-2010 average). • Since 2005, new global record temperatures have been set in 2010 and then in each successive year 2014, 2015 and 2016. In these last three record years the global average temperature anomaly was 0.31,0.44, 0.56°C higher than the 1981-2010 average. • 2014 was a record warm year for coastal air and sea temperatures around the UK. Between 1984 and 2014 coastal water temperatures rose around the UK at an average rate of 0.28 °C/decade. The rate varies between regions, the slowest warming was in the Celtic Sea at 0.17 °C/decade and the maximum rate was in the Southern North Sea at 0.45 °C/decade. • There is also variability over shorter time periods. In all regions of UK seas there was a negative trend in the 10-year period between 2003 and 2013. This is due to variability within the ocean /atmosphere system which is natural. • There is a trend towards fewer in-situ observations, and this will ultimately influence the confidence in future assessments. • Some gridded datasets can offer alternatives to single point observations, but to understand the patterns of ocean variability, the quality information from ocean timeseries cannot yet be replaced by surface observations or autonomous data collection. • The first MCCIP report card in 2006 used the UKCIP projections from 2002 which had a very limited representation of the SST. • The latest updates to the UK Climate Projections shelf seas models were published in 2016 and projected increases in sea surface temperature for 2069-89 relative to 1960-89 of over 3 °C for most of the North Sea, English Channel, Irish and Celtic Seas. For the deeper areas to the north and west of Scotland out towards Rockall and in the Faroe Shetland Channel the increase in temperature is projected to be closer to 2 °C. • Over the last 10 years there has been a steady improvement in the scientific basis underlying centennial sea temperature projections for the seas around the UK, and significant progress in the field of seasonal and decadal projections. • The scientific basis to such projections and predictions will continue to improve over the next 10 years, with increasing resolution, treatment of climate uncertainties, and methodology. Over the centennial scale the difference between emissions scenarios are still the source of the largest uncertainties. • Development of North West European Shelf (NWS) modelling systems driven by seasonal forecasting systems may allow NWS temperature prediction over the monthly to decadal period

    Social determinants of ethnic disparities in SARS-CoV-2 infection: UK Biobank SARS-CoV-2 Serology Study

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    Background: The social determinants of ethnic disparities in risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK remain unclear. Methods: In May 2020, a total of 20 195 adults were recruited from the general population into the UK Biobank SARS-CoV-2 Serology Study. Between mid-May and mid-November 2020, participants provided monthly blood samples. At the end of the study, participants completed a questionnaire on social factors during different periods of the pandemic. Logistic regression yielded ORs for the association between ethnicity and SARS-CoV-2 immunoglobulin G antibodies (indicating prior infection) using blood samples collected in July 2020, immediately after the first wave. Results: After exclusions, 14 571 participants (mean age 56; 58% women) returned a blood sample in July, of whom 997 (7%) had SARS-CoV-2 antibodies. Seropositivity was strongly related to ethnicity: compared with those of White ethnicity, ORs (adjusted for age and sex) for Black, South Asian, Chinese, Mixed and Other ethnic groups were 2.66 (95% CI 1.94–3.60), 1.66 (1.15–2.34), 0.99 (0.42–1.99), 1.42 (1.03–1.91) and 1.79 (1.27–2.47), respectively. Additional adjustment for social factors reduced the overall likelihood ratio statistics for ethnicity by two-thirds (67%; mostly from occupational factors and UK region of residence); more precise measurement of social factors may have further reduced the association. Conclusions: This study identifies social factors that are likely to account for much of the ethnic disparities in SARS-CoV-2 infection during the first wave in the UK, and highlights the particular relevance of occupation and residential region in the pathway between ethnicity and SARS-CoV-2 infection

    A time-resolved Förster resonance energy transfer assay to investigate drug and inhibitor binding to ABCG2

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    The human ATP-binding cassette (ABC) transporter, ABCG2, is responsible for multidrug resistance in some tumours. Detailed knowledge of its activity is crucial for understanding drug transport and resistance in cancer, and has implications for wider pharmacokinetics. The binding of substrates and inhibitors is a key stage in the transport cycle of ABCG2. Here, we describe a novel binding assay using a high affinity fluorescent inhibitor based on Ko143 and time-resolved Förster resonance energy transfer (TR-FRET) to measure saturation binding to ABCG2. This binding is displaced by Ko143 and other known ABCG2 ligands, and is sensitive to the addition of AMP-PNP, a non-hydrolysable ATP analogue. This assay complements the arsenal of methods for determining drug:ABCG2 interactions and has the possibility of being adaptable for other multidrug pumps

    Thermohaline forcing and interannual variability of northwestern inflows into the northern North Sea

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    A long-established, 127 km-long hydrographic section in the northern North Sea at 59.28°N that runs from the eastern coast of Orkney (2.23°W) to the central North Sea (0°) crosses the path of the main inflows of Atlantic water. Data from 122 occupations between 1989 and 2015 are examined to determine the annual cycle and long-term trends of temperature, salinity and depth-varying geostrophic flow across the section. In an average year, the geostrophic flow referenced to the seafloor is at its narrowest (40 km) in winter, during which time it is driven by the strong horizontal salinity gradient; the horizontal temperature gradient is very weak. Velocity exceeds 4 cm s−1, but transport is at a minimum (0.11 Sv). In the deeper water in the east of the section, thermal stratification develops throughout summer and persists until October, whereas the west is tidally mixed all year. The bottom temperature gradient becomes the primary driver of the geostrophic flow, which is fastest (9 cm s−1) in September and broadest (100 km) in October. Maximum transport (0.36 Sv) occurs in October. Throughout the summer, the horizontal salinity gradient weakens, as does its contribution to the flow. However, it nevertheless acts to broaden the flow west of the location of the strongest horizontal temperature gradient. Section-mean de-seasoned temperature is found to be positively correlated to the Atlantic Multidecadal Oscillation and negatively correlated to the North Atlantic Oscillation. These results refine our understanding of the thermohaline forcing of Atlantic inflow into the northern North Sea, particularly in relation to the salinity distribution. Understanding the variability of this inflow is important for understanding the dynamics of the North Sea ecosystem
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