48 research outputs found

    Vibration monitoring and condition assessment of the University of Sheffield Arts Tower during retrofit

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s13349-012-0028-xThe 78 m Arts Tower at the University of Sheffield was refurbished during the period 2009-2011, with improvements that included replacement of façades and partitions. The structural changes were reflected in changes in dynamic properties that were tracked by a combination of long-term acceleration monitoring and vibration tests to identify local and global vibration modes. The global horizontal plane modes of the building were correlated with finite element model simulations and real-time automated operational modal analysis to characterize the effects of the structural changes on horizontal vibration modes in sway and torsion. In addition, floor vibration tests linked to the finite element simulations identified the contribution of 'non-structural partitions' on the floor dynamic performance. Replacement of heavy masonry partitions with modern lightweight forms has resulted in reduction of stiffness, yet there is no obvious change in sway vibration serviceability and floor performance remains satisfactory. © 2013 Springer-Verlag Berlin Heidelberg

    The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

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    <p>Abstract</p> <p>Background</p> <p>Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function.</p> <p>Methods</p> <p>Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A<sub>2</sub>, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise.</p> <p>Results</p> <p>Our results during exercise showed a) platelet activation (increased thromboxane B<sub>2</sub>, TXB<sub>2</sub>), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups).</p> <p>Conclusion</p> <p>Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB<sub>2 </sub>levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications.</p

    Comparison of the ligand‐binding properties of fluorescent VEGF‐A isoforms to VEGF receptor 2 in living cells and membrane preparations using NanoBRET

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    Background and Purpose: Vascular Endothelial Growth Factor A (VEGF-A) is a key mediator of angiogenesis. A striking feature of the binding of a fluorescent analogue of VEGF165a to NanoLuciferase-tagged VEGF Receptor 2 (VEGFR2) in living cells is that the bioluminescence resonance energy transfer (BRET) signal is not sustained and declines over time. This may be secondary to receptor internalisation. Here we have compared the binding of three fluorescent VEGF-A isoforms to VEGFR2 in cells and isolated membrane preparations.Experimental Approach: Ligand binding kinetics were monitored in both intact HEK293T cells and membranes (expressing NanoLuciferase tagged VEGFR2) using BRET between the tagged receptor and fluorescent analogues of VEGF165a, VEGF165b and VEGF121a. VEGFR2 endocytosis in intact cells expressing VEGFR2 was monitored by following the appearance of fluorescent ligand-associated receptors in intracellular endosomes using automated quantitative imaging.Key Results: Quantitiative analysis of the effect of fluorescent VEGF-A isoforms onVEGFR2 endocytosis in cells demonstrated that they produced a rapid and potent translocation of ligand-bound VEGFR2 into intracellular endosomes. NanoBRET can be used to monitor the kinetics of the binding of fluorescent VEGF-A isoforms to VEGFR2. In isolated membrane preparations, ligand binding association curves were maintained for the duration of the 90 minute experiment. Measurement of koff at pH 6.0 in membrane preparations indicated shorter ligand residence times than those obtained at pH 7.4.Conclusions and Implications: These studies suggest that rapid VEGF-A isoform-induced receptor endocytosis shortens agonist residence times on the receptor (1/koff) as VEGFR2 moves from the plasma membrane to intracellular endosomes

    Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium

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    Background: One of the most prevalent microvascular complications for patients with diabetes is diabetic retinopathy (DR) associated with increased retinal endothelial blood vessel formation. Treatments to reduce vascularisation in the retinal endothelium are linked to improved sight in patients with DR. Recently we have demonstrated the novel protective role of the artificial sweetener, sucralose, and the sweet taste receptor, T1R3, in the pulmonary endothelium to reduce vascular leak. In the present study, we examined the role of sucralose and sweet taste receptors on vasculogenic processes (proliferation, migration, adhesion and tube formation) in a cell model of the retinal endothelium . Methods: We exposed human retinal microvascular endothelial cells (RMVEC) to VEGF as an in vitro model of DR in the presence and absence of T1R3 agonist sucralose. Results: In RMVEC, we observed increased VEGF-induced cell proliferation, migration, adhesion and tube formation, which was significantly attenuated by exposure to the artificial sweetener sucralose. Following siRNA knockdown of the sweet taste receptor, T1R3, but not T1R2, the protective effect of sucralose on VEGF-induced RMVEC vasculogenic processes was blocked. We further demonstrate that sucralose attenuates VEGF-induced Akt phosphorylation to protect the retinal microvasculature. Conclusion: These studies are the first to demonstrate a protective effect of an artificial sweetener, through the sweet taste receptor T1R3, on VEGF-induced vasculogenesis in a retinal microvascular endothelial cell line

    Nicotine dependence and loss of autonomy among Greek adolescent smokers: A countrywide cross-sectional study

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    Nicotine dependence is one of the main reasons for the continuation of smoking among adolescents. Loss of autonomy (LOA) is a measure of dependence. This study is the first to investigate LOA and its determinants among Greek adolescents. In 2013, 13-to-15-year-old middle-school students were selected by multi-stage clustered sampling. LOA was evaluated with the Hooked-on-Nicotine Checklist (HONC). Multiple univariate analysis was used to assess the association between adolescent demographics, smoking habits, and loss of autonomy. Three-hundred thirty-nine current smokers responded to the questionnaire (response rate: 82.3%). Of these respondents, 51.2% were male and 88.8% reported at least one LOA symptom. The mean HONC score was 4.13/10 (95% CI: 3.82–4.45). Higher scores were negatively associated with lower smoking frequency (cumulative odds ratio (cOR): 0.240, 95% CI: 0.144–0.400) and positively associated with lower age at first cigarette (cOR: 2.29, 95% CI: 1.38–3.82). Female gender was significantly associated with the prevalence but not the degree of LOA. Overall, the prevalence and the degree of nicotine dependence among adolescent smokers in Greece is similar to other countries. Frequent smoking and initiation of smoking at a younger age are linked to nicotine dependence, although it was not possible to make causal inferences. The relationship between nicotine dependence and gender remains unclear. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

    Evaluation of a two-step ultrasound examination protocol for the detection of major fetal structural defects

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    Objective: To evaluate a two-step screening protocol of ultrasound examinations (1114 and 2024 weeks) for the detection of major fetal structural defects. Methods: Retrospective study in a private maternity hospital. Women with viable singleton pregnancies having both first trimester scan and anomaly scan at our department and subsequently delivered at our hospital were included. Major fetal structural defects were defined as those requiring medical or surgical treatment or those causing mental handicap. Results: A total of 3,902 pregnancies included 61 fetuses with structural defects (1.56%). Twenty-six (42.6%) were diagnosed in the first trimester and 29 (47.5%) in the second. Six anomalies were detected in the third trimester or after birth. Overall detection rate of the two-step program was 90.2%. Conclusions: Detailed examination of fetal anatomy at 1114 weeks resulted in the early diagnosis of about 40% of major structural defects © 2012 Informa UK, Ltd
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