97 research outputs found

    Analysis of a civil aircraft wing transonic shock buffet experiment

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    The physical mechanism governing the onset of transonic shock buffet on swept wings remains elusive, with no unequivocal description forthcoming despite over half a century of research. This paper elucidates the fundamental flow physics on a civil aircraft wing using an extensive experimental database from a transonic wind tunnel facility. The analysis covers a wide range of flow conditions at a Reynolds number of around . Data at pre-buffet conditions and beyond onset are assessed for Mach numbers between 0.70 and 0.84. Critically, unsteady surface pressure data of high spatial and temporal resolution acquired by dynamic pressure-sensitive paint is analysed, in addition to conventional data from pressure transducers and a root strain gauge. We identify two distinct phenomena in shock buffet conditions. First, we highlight a low-frequency shock unsteadiness for Strouhal numbers between 0.05 and 0.15, based on mean aerodynamic chord and reference free stream velocity. This has a characteristic wavelength of approximately 0.8 semi-span lengths (equivalent to three mean aerodynamic chords). Such shock unsteadiness is already observed at low-incidence conditions, below the buffet onset defined by traditional indicators. This has the effect of propagating disturbances predominantly in the inboard direction, depending on localised separation, with a dimensionless convection speed of approximately 0.26 for a Strouhal number of 0.09. Second, we describe a broadband higher-frequency behaviour for Strouhal numbers between 0.2 and 0.5 with a wavelength of 0.2 to 0.3 semi-span lengths (0.6 to 1.2 mean aerodynamic chords). This outboard propagation is confined to the tip region, similar to previously reported buffet cells believed to constitute the shock buffet instability on conventional swept wings. Interestingly, a dimensionless outboard convection speed of approximately 0.26, coinciding with the low-frequency shock unsteadiness, is found to be nearly independent of frequency. We characterise these coexisting phenomena by use of signal processing tools and modal analysis of the dynamic pressure-sensitive paint data, specifically proper orthogonal and dynamic mode decomposition. The results are scrutinised within the context of a broader research effort, including numerical simulation, and viewed alongside other experiments. We anticipate our findings will help to clarify experimental and numerical observations in edge-of-the-envelope conditions and to ultimately inform buffet-control strategies

    TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2)

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    BACKGROUND AND AIMS: TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular pathway with potential for acute coronary syndrome (ACS) and major adverse cardiovascular events (MACE) prediction. METHODS: Blood samples were obtained from consecutive patients (n = 229) with coronary angiographic evidence of CAD admitted with ACS or electively. MACE were recorded after a median 3-year follow-up. Controls (n = 115) had a <10% CAD risk as per the HeartSCORE. TACE and TIMP3 protein and mRNA levels were measured by ELISA and RT-qPCR respectively. TACE substrates were measured using a multiplex proximity extension assay. RESULTS: TACE mRNA and cell protein levels (p < 0.01) and TACE substrates LDLR (p = 0.006), TRANCE (p = 0.045), LAG-3 (p < 0.001) and ACE2 (p < 0.001) plasma levels were significantly higher in CAD patients versus controls. TACE inhibitor TIMP3 mRNA levels were significantly lower in CAD patients and tended to be lower in the ACS population (p < 0.05). TACE substrates TNFR1 (OR:3.237,CI:1.514–6.923,p = 0.002), HB-EGF (OR:0.484,CI:0.288–0.813,p = 0.006) and Ep-CAM (OR:0.555,CI:0.327–0.829,p = 0.004) accurately classified ACS patients with HB-EGF and Ep-CAM levels being lower compared to electively admitted patients. TNFR1 (OR:2.317,CI:1.377–3.898,p = 0.002) and TNFR2 (OR:1.902,CI:1.072–3.373,p = 0.028) were significantly higher on admission in those patients who developed MACE within 3 years. CONCLUSIONS: We demonstrate a possible role of TACE substrates LAG-3, HB-EGF and Ep-CAM in atherosclerotic plaque development and stability. We also underline the importance of measuring TNFR1 and TNFR2 earlier than previously appreciated for MACE prediction. We report an important role of TIMP3 in regulating TACE levels

    Intracoronary EnalaPrilat to Reduce MICROvascular Damage During Percutaneous Coronary Intervention (ProMicro) study.

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    Intracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation. Methods We randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 g) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury. Results Infusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 11 at baseline vs. 19 9 after drug vs. 15 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 15 at baseline vs. 24 15 after drug vs. 33 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p 0.025). Conclusions Intracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedurerelated injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit. (J Am Coll Cardiol 2013;61:615–21) © 2013 by the American College of Cardiology Foundatio

    The importance of context: an exploration of factors influencing the adoption of student-centered teaching among chemistry, biology, and physics faculty

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    Background: Research at the secondary and postsecondary levels has clearly demonstrated the critical role that individual and contextual characteristics play in instructors’ decision to adopt educational innovations. Although recent research has shed light on factors influencing the teaching practices of science, technology, engineering, and mathematics (STEM) faculty, it is still not well understood how unique departmental environments impact faculty adoption of evidence-based instructional practices (EBIPs) within the context of a single institution. In this study, we sought to characterize the communication channels utilized by STEM faculty, as well as the contextual and individual factors that influence the teaching practices of STEM faculty at the departmental level. Accordingly, we collected survey and observational data from the chemistry, biology, and physics faculty at a single large research-intensive university in the USA. We then compared the influencing factors experienced by faculty in these different departments to their instructional practices. Results: Analyses of the survey data reveal disciplinary differences in the factors influencing adoption of EBIPs. In particular, the physics faculty (n = 15) had primarily student-centered views about teaching and experienced the most positive contextual factors toward adoption of EBIPs. At the other end of the spectrum, the chemistry faculty (n = 20) had primarily teacher-centered views and experienced contextual factors that hindered the adoption of student-centered practices. Biology faculty (n = 25) fell between these two groups. Classroom observational data reflected these differences: The physics classrooms were significantly more student-centered than the chemistry classrooms. Conclusions: This study demonstrates that disciplinary differences exist in the contextual factors teaching conceptions that STEM faculty experience and hold, even among faculty within the same institution. Moreover, it shows that these differences are associated to the level of adoption of student-centered teaching practices. This work has thus identified the critical need to carefully characterize STEM faculty’s departmental environment and conceptions about teaching before engaging in instructional reform efforts, and to adapt reform activities to account for these factors. The results of this study also caution the over generalization of findings from a study focused on one type of STEM faculty in one environment to all STEM faculty in any environment

    Rif1 maintains telomeres and mediates DNA repair by encasing DNA ends

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    In yeast, Rif1 is part of the telosome, where it inhibits telomerase and checkpoint signaling at chromosome ends. In mammalian cells, Rif1 is not telomeric, but it suppresses DNA end resection at chromosomal breaks, promoting repair by nonhomologous end joining (NHEJ). Here, we describe crystal structures for the uncharacterized and conserved ∌125-kDa N-terminal domain of Rif1 from Saccharomyces cerevisiae (Rif1-NTD), revealing an α-helical fold shaped like a shepherd's crook. We identify a high-affinity DNA-binding site in the Rif1-NTD that fully encases DNA as a head-to-tail dimer. Engagement of the Rif1-NTD with telomeres proved essential for checkpoint control and telomere length regulation. Unexpectedly, Rif1-NTD also promoted NHEJ at DNA breaks in yeast, revealing a conserved role of Rif1 in DNA repair. We propose that tight associations between the Rif1-NTD and DNA gate access of processing factors to DNA ends, enabling Rif1 to mediate diverse telomere maintenance and DNA repair functions

    Social interactions in urban public places: participative method and recruitment strategies

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    This research focuses on the use of different public (and pseudo-public) spaces in urban areas.1 It draws on a case study of a year-long research project in the town of Aylesbury in southeast England, a market town with a population of around 69,000. The study set out to examine how different people use public spaces and to analyse how social interactions vary by age, gender or place. What it does not do, is reflect what is known about these different groups’ use of other ‘spaces’, for example their own homes and other indoor facilities. The findings were considered in terms of their relevance for emerging policy agendas on shared and contested spaces, intergenerational relationships, safety and security, and the management of public space. The project is based on a mixed-methods approach, which involved discussion with a wide range of stakeholders in the town, from local politicians and community leaders to business owners and managers; street surveys with members of the public at a range of observations sites; and non-participant observation at nine sites, undertaken by 46 members of the general public (aged 16-73 years) over a 12-month period (October 2004 to September 2005). The observations were carried out in three types of public spaces: residential neighbourhoods, green open spaces and town centre spaces, which were considered representative of the town’s public spaces as a whole. The observations were carried out across the day from 7am to 1am. The research method was highly participatory, with the observers also contributing to and informing the data analysis

    Food environments: From home to hospital

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